Molecular mechanisms of pelvic organ prolapse influenced by FBLN5 via FOSL1/miR-222/MEIS1/COL3A1 axis.
This study delves into the role of FBLN5 in pelvic organ prolapse (POP) and its molecular mechanisms, focusing on the FOSL1/miR-222/MEIS1/COL3A1 axis. Gene relationships linked to POP were confirmed using bioinformatics databases like GEO and StarBase. Primary human uterosacral ligament fibroblasts (hUSLF) were extracted and subjected to mechanical stretching. Cellular cytoskeletal changes were examined via phalloidin staining, intracellular ROS levels with a ROS kit, cell apoptosis through flow cytometry, and cell senescence using β-galactosidase staining. FBLN5's downstream targets were identified, and the interaction between FOSL1 and miR-222 and miR-222 and MEIS1 were validated using assays. In rat models, the role of FBLN5 in POP was assessed using bladder pressure tests. Results indicated diminished FBLN5 expression in uterine prolapse. Enhanced FBLN5 countered mechanical damage in hUSLF cells by downregulating FOSL1. FOSL1 augmented miR-222, inhibiting MEIS1, which subsequently fostered COL3A1 transcription. In rat models, the absence of FBLN5 exacerbated POP by influencing the FOSL1/miR-222/MEIS1/COL3A1 pathway. FBLN5's protective role likely involves regulating the above axis and boosting COL3A1 expression. Further research is needed to validate the effectiveness and safety of this mechanism in human patients and to propose potential new treatment options.


Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.
Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.


[Medical standards of out- and inpatient care in otorhinolaryngology].
To improve the quality of out- and inpatient care in otorhinolaryngology, the authors propose standard minimum of medical measures (preventive, diagnostic and therapeutic) which should be taken in each nosological entity of ENT pathology. It is emphasized that medical standards should be adjusted to the disease peculiarities, possible atypical course, etc., but the scope of diagnostic and therapeutic care should not be less than the standard list of measures. Deviation from the standards is a criterion of medical service imperfection.


Transcutaneous bilirubinometry. I. Correlations in term infants.
The transcutaneous bilirubinometer was evaluated in 43 white infants, eight black infants, and in nine white infants treated with phototherapy. The reproducibility of the instruments was determined after trials consisting of both five and 100 repetitions. Among the infants not being treated with phototherapy, TcB index and serum bilirubin concentration correlated at 0.90 level in both white and black infants. Phototherapy reduced the accuracy of the TcB and, at the present time, the use of this index in infants under light therapy cannot be recommended. Otherwise the TcB is a valuable tool in screening healthy term infants for hyperbilirubinemia.


Virus-specific CD8+ T cells in the liver: armed and ready to kill.
Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8+ T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8+ T cells specific for the immunodominant H2D(b)NP(366-374) (D(b)NP(366)) epitope. Functional analysis established that these liver-derived virus-specific CD8+ T cells are fully competent cytotoxic effectors and IFN-gamma secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8+ T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8+ T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a "graveyard" for influenza virus-specific CD8+ T cells.


Structure and properties of a complex of α-synuclein and a single-domain camelid antibody.
The aggregation of the intrinsically disordered protein α-synuclein to form fibrillar amyloid structures is intimately associated with a variety of neurological disorders, most notably Parkinson's disease. The molecular mechanism of α-synuclein aggregation and toxicity is not yet understood in any detail, not least because of the paucity of structural probes through which to study the behavior of such a disordered system. Here, we describe an investigation involving a single-domain camelid antibody, NbSyn2, selected by phage display techniques to bind to α-synuclein, including the exploration of its effects on the in vitro aggregation of the protein under a variety of conditions. We show using isothermal calorimetric methods that NbSyn2 binds specifically to monomeric α-synuclein with nanomolar affinity and by means of NMR spectroscopy that it interacts with the four C-terminal residues of the protein. This latter finding is confirmed by the determination of a crystal structure of NbSyn2 bound to a peptide encompassing the nine C-terminal residues of α-synuclein. The NbSyn2:α-synuclein interaction is mediated mainly by side-chain interactions while water molecules cross-link the main-chain atoms of α-synuclein to atoms of NbSyn2, a feature we believe could be important in intrinsically disordered protein interactions more generally. The aggregation behavior of α-synuclein at physiological pH, including the morphology of the resulting fibrillar structures, is remarkably unaffected by the presence of NbSyn2 and indeed we show that NbSyn2 binds strongly to the aggregated as well as to the soluble forms of α-synuclein. These results give strong support to the conjecture that the C-terminal region of the protein is not directly involved in the mechanism of aggregation and suggest that binding of NbSyn2 could be a useful probe for the identification of α-synuclein aggregation in vitro and possibly in vivo.


Psychometric properties of the finding a balance scale for family caregivers of elders with dementia in Taiwan.
The Finding a Balance Scale, designed to measure the degree to which caregivers can balance the competing demands of caregiving and other priorities, assists health care providers in understanding the process of family caregiving. The aim of this study was to examine the scale's psychometric properties and determine an appropriate cutoff score for identifying caregivers at high risk for poor caregiving consequences. We found adequate reliabilities and appropriate validities in a convenience sample of 197 family caregivers of elders with dementia in Taiwan. The optimal cutoff was also determined. The validated Finding a Balance Scale provides an assessment tool to explore the competing responsibilities, conditions, and difficulties for family caregivers of elders with dementia in Taiwan.


Gingival crevicular fluid semaphorin 4D and peptidylarginine deiminase-2 levels in periodontal health and disease.
The aim of this study was to compare the levels of semaphorin 4D (SEMA4D), peptidylarginine deiminase 2 (PAD2) and matrix metalloproteinase-8 (MMP-8) in gingival crevicular fluid (GCF) in patients with periodontal disease and patients with healthy periodontium and investigate the effects of periodontal treatment on the levels of these molecules. GCF samples were collected from periodontally healthy controls (C group, n = 20), patients with gingivitis (G group, n = 20), and patients with chronic periodontitis (CP group, n = 20). Sampling sites were also divided into bleeding (BP) and non-bleeding (NBP) periodontal pocket groups in CP group. Full-mouth clinical periodontal parameters were also recorded. GCF samplings and clinical records were also repeated at 1 and 3 months after treatment for the CP group. SEMA4D, PAD2, and MMP-8 levels were determined by enzyme-linked immunosorbent assay. The GCF SEMA4D, PAD2, and MMP-8 total amounts were similar in CP and G groups (P ˃ 0.05) but significantly greater than the C group (P ˂ 0.05). The GCF SEMA4D and PAD2 total amounts in the BP group were significantly greater than the NBP group (P ˂ 0.05). GCF MMP-8 total amounts were similar in BP and NBP groups (P ˃ 0.05). The GCF SEMA4D, PAD2, and MMP-8 total amounts were significantly reduced at first month after treatment (P ˂ 0.05). There were positive correlations between GCF total amount of SEMA4D and all clinical parameters (P ˂ 0.01) and also between PAD2 and clinical parameters (P ˂ 0.05) except clinical attachment level. There was a positive correlation between GCF total amount of SEMA4D and GCF total amount of MMP-8 (P ˂ 0.05). It may be suggested that SEMA4D and PAD2 are related to periodontal disease. Their GCF total amounts may have a diagnostic potential. Additional studies would better clarify their role in periodontal diseases.


eHealth for people with COPD in the Netherlands: a scoping review.
Background: In the Netherlands, almost 600,000 people had chronic obstructive pulmonary disease (COPD) in 2017. This decreases quality of life for many and each year, COPD leads to approximately 6,800 deaths and about one billion health care expenditures. It is expected that eHealth may improve access to care and reduce costs. However, there is no conclusive scientific evidence available of the added value of eHealth in COPD care. We conducted a scoping review into the use of eHealth in Dutch COPD care. The aim of the research was to provide an overview of all eHealth applications used in Dutch COPD care and to assess these applications on a number of relevant criteria. Methods: In order to make an overview of all eHealth applications aimed at COPD patients in the Netherlands, literature was searched in the electronic databases PubMed and Google Scholar. In addition, Dutch health care websites were searched for applications that have been evaluated for effectiveness and reliability. The identified eHealth applications were assessed according to five relevant quality criteria, eg, whether research has been conducted on the effectiveness. Results: Thirteen health care programs and patient platforms in COPD care have been found that use eHealth. In addition, 13 self-care and informative websites and 15 mobile apps were found that are available to citizens and patients. Five of 13 care programs and patient platforms were found to be effective in improving quality of life or reducing hospital admissions in small pilot studies. The effectiveness of these and the other eHealth applications should be established in larger studies in the future. Discussion: More research into the effectiveness of eHealth applications for COPD patients is needed. We recommend to develop a nationwide open source platform where well-evaluated eHealth applications can be showcased for patients and health care providers to improve COPD care.


Induction of human trophoblast stem cells.
Cell reprogramming has allowed unprecedented access to human development, from virtually any genome. However, reprogramming yields pluripotent stem cells that can differentiate into all cells that form a fetus, but not extraembryonic annexes. Therefore, a cellular model allowing study of placental development from a broad genomic repertoire is lacking. Here, we describe an optimized protocol to reprogram somatic cells into human induced trophoblast stem cells (hiTSCs) and convert pluripotent stem cells into human converted TSCs (hcTSCs). This protocol enables much-needed genome-specific placental disease modeling. We also detail extravillous trophoblast and syncytiotrophoblast differentiation protocols from hiTSCs and hcTSCs, a necessary step to validate these cells. In total, this protocol takes 4 months and requires advanced cell culture skills, comparable to those necessary for somatic cell reprogramming into human induced pluripotent stem cells.


The uses and limits of standard exercise tests.
Standard exercise electrocardiography to detect coronary artery disease involves limitations of accuracy in a population of apparently healthy persons, to the extent that its value for counseling such individuals is doubtful. Among subjects being examined for chest pain, however, the accuracy of the exercise ECG in predicting coronary obstructive disease is better. In addition, the presence of more severe coronary obstructive disease tends to be associated with more distinctly abnormal tests at low levels of exercise. This tendency of association between marked ST-segment displacement at low exertion levels and more severe obstructive disease adds a measure of prognostic value to the standard exercise ECG in persons with chest pain or after myocardial infarction. The addition of either isotopic cardiac imaging or coronary arteriography to exercise ECG will be appropriate for situations in which either the ECG is known to be nonspecific or inadequate exercise is achieved.


Long-term anti-itch effect of botulinum neurotoxin A is associated with downregulation of TRPV1 and TRPA1 in the dorsal root ganglia in mice.
Itch is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-itch effects of the botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in mice. Furthermore, a single injection of BoNT/A reduced the expression of the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), and the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) at both transcriptional and translational levels in the dorsal root ganglia (DRG) in mice. Pretreatment of BoNT/A also attenuated chronic itch induced by acetone-diethylether-water treatment and abolished the upregulation of TRPA1 in the DRG. Thus, it was suggested that downregulation of the expression of TRPA1 and TRPV1 in the DRG may contribute toward the long-term anti-itch effects of a single injection of BoNT/A in mice and BoNT/A treatment may serve as an alternative strategy for anti-itch therapy.


High Prevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in Children with Acute Respiratory Infections from Lima, Peru.
Mycoplasma pneumoniae and Chlamydia pneumoniae are atypical pathogens responsible for pneumonia and a leading cause of morbidity and mortality in low income countries. The study objective is to determine the prevalence of this pathogens in Peruvian children with acute respiratory infections. A consecutive cross-sectional study was conducted in Lima, Peru from May 2009 to September 2010. A total of 675 children admitted with clinical diagnoses of acute respiratory infections were tested for Mycoplasma pneumoniae and Chlamydia pneumoniae detection by polymerase chain reaction (PCR), and clinical symptoms were registered by the attending physician. Mycoplasma pneumonia was detected in 25.19% (170/675) of nasopharyngeal samples and Chlamydia pneumonia in 10.52% (71/675). The most common symptoms in patients with these atypical pathogens were rhinorrhea, cough and fever. A higher prevalence of Mycoplasma pneumoniae cases were registered in summer, between December 2009 and March 2010. Mycoplasma pneumoniae and Chlamydia pneumonia are a significant cause of morbidity in Peruvian children with acute respiratory infections (ARI). Further studies should evaluate the use of reliable techniques such as PCR in Peru in order to avoid underdiagnoses of these atypical pathogens.


Influence of the application of three different elicitors on soybean plants on the concentrations of several isoflavones in soybean seeds.
Soybean [Glycine max (L.) Merr.] is a rich source of isoflavones that are often affected by biotic and abiotic factors. The objectives of this study were to evaluate the effect of various concentrations of three natural elicitors applied at different soybean growth stages on isoflavone content and to compare the efficiency of several solvent systems in isoflavone extraction and quantification. The isoflavones extracted from R96-3444 soybean using eight solvent systems were separated, identified, and quantified by a high-performance liquid chromatography (HPLC) procedure. The soybean plants were sprayed with salicylic acid, methyl salicylate, or ethyl acetate at 0, 10(-6), 10(-3), and 10(-1) M at R1 (blooming) or R4 (full pods) growth stage. Results showed that 10(-3) M ethyl acetate sprayed at the R1 stage significantly increased total isoflavone content and the levels of some individual isoflavones in soybean seeds. With all the elicitors that were tested, concentration was a more important factor than application time with respect to isoflavone content with lower concentrations being more effective on most isoflavones. A 53% acetonitrile solvent system was the best solvent system for extracting total isoflavone, malonyl glucosides, genistein, glycitin, genistin, acetyl-daidzin, and acetyl-genistin. The results of this study will be useful for increasing the isoflavone content in desirable soybean varieties and improving isoflavone concentration during extraction.


Comparative evaluation of diode laser ablation and surgical stripping technique for gingival depigmentation: A clinical and immunohistochemical study.
There are various treatment modalities to remove the black patches of melanin pigmentation. The aim of the study is to clinically compare the diode laser ablation and surgical stripping technique for gingival depigmentation and to evaluate their effect on the histological changes in melanocyte activity. A total of 40 sites of 20 patients with bilateral melanin hyperpigmentation were treated with the surgical stripping and diode laser ablation technique. Change in Hedin index score, change in area of pigmentation using image analyzing software, pain perception, patient preference of treatment were recorded. All 40 sites were selected for immunohistochemical analysis using HMB-45 immunohistochemical marker. At 12 months post-operative visit, in all sites, repigmentation was observed with different grades of Hedin index. Paired t-test, analysis of variance, and Chi-square tests were used for statistical analysis. Repigmentation in surgical stripping is significantly lesser compared to laser ablation. Lesser numbers of melanocytes were found on immunohistological examination at 12 months postoperatively. Comparison for patient preference and pain indices give statistically significant values for diode laser techniques. Gingival hyperpigmentation is effectively managed by diode laser ablation technique and surgical stripping method. In this study, surgical stripping technique found to be better compared to diode laser ablation.


Calliope-Net: Automatic Generation of Graph Data Facts via Annotated Node-link Diagrams.
Graph or network data are widely studied in both data mining and visualization communities to review the relationship among different entities and groups. The data facts derived from graph visual analysis are important to help understand the social structures of complex data, especially for data journalism. However, it is challenging for data journalists to discover graph data facts and manually organize correlated facts around a meaningful topic due to the complexity of graph data and the difficulty to interpret graph narratives. Therefore, we present an automatic graph facts generation system, Calliope-Net, which consists of a fact discovery module, a fact organization module, and a visualization module. It creates annotated node-link diagrams with facts automatically discovered and organized from network data. A novel layout algorithm is designed to present meaningful and visually appealing annotated graphs. We evaluate the proposed system with two case studies and an in-lab user study. The results show that Calliope-Net can benefit users in discovering and understanding graph data facts with visually pleasing annotated visualizations.


The glycogen-depleting effect of exogenous maternal epinephrine on the liver of the fetal rat during the sixteenth day of gestation.
The effect of 1-epinephrine administered I. P. to pregnant rats during sodium pentobarbital anesthesia on fetal liver glycogen levels has been investigated. Sodium pentobarbital (22 mg./kg. maternal body weight) was administered I. P. to all pregnant rats in the control group and each 1-epinephrine dosage group twenty minutes prior to the surgical removal of the fetuses. L-epinephrine (10, 20 or 30 micrograms/kg. maternal body weight) given ten minutes after the administration of the barbiturate reduced the fetal liver glycogen levels significantly. The glycogen-depleting effect of 1-epinephrine on the fetal liver in the rat was found to be dosage-dependent.


Exploring the dual functionality of an ytterbium complex for luminescence thermometry and slow magnetic relaxation.
We present a comprehensive investigation of the magnetic and optical properties of an ytterbium complex, which combines two desirable and practical features into a single molecular system. Based upon YbIII ions that promote near-infrared optical activity and a chemical backbone that is ideal for an in-depth understanding of the magnetic behaviour, we have designed a multifunctional opto-magnetic species that operates as a luminescent thermometer and as a single-molecule magnet (SMM). Our magnetic investigations, in conjunction with ab initio calculations, reveal one of the highest energy barriers reported for an YbIII-based complex. Moreover, we correlate this anisotropic barrier with the emission spectrum of the compound, wherein we provide a complete assignment of the energetic profile of the complex. Such studies lay the foundation for the design of exciting multi-faceted materials that are able to retain information at the single-molecule level and possess built-in thermal self-monitoring capabilities.


[Comparative changes in sedimentation rate, haptoglobin and orosomucoid during the development of rhizomelic pseudopolyarthritis and temporal arteritis. Attempted definition of the biological parameters for monitoring these diseases].
In pseudo-polyarthritis of the extremities as well as in temporal arteritis we have noted a very marked correlation between sedimentation rate (ESR) and inflammatory proteins at the beginning of the disease. By contrast there is a dissociation during the course of the illness and sometimes at the time of onset in those rare forms with a normal ESR. It was therefore concluded that the ESR was not sufficiently accurate as an index of surveillance in such diseases. Study of inflammation proteins is in rare circumstances of diagnostic value at the time of onset of the disorder, in forms with a normal ESR. Comparative study of their variations with that in ESR would appear to provide an accurate factor in surveillance during the course for peripheral pseudo-polyarthritis and temporal arteritis. At that time, even though a return to a satisfactory clinical state and a normal ESR may be accompanied by a persistent increase in such proteins, it is not felt to be desirable to attempt to obtain their normalization. Finally, it would appear that their return to normal at the end of the course of the disease provides a reliable test of cure.


An exploratory study of the patients' sleep patterns and inflammatory response following cardiopulmonary bypass (CPB).
To describe sleep patterns and inflammatory response postCPB, determine sleep pattern changes and inflammatory response over time and explore relationships between sleep and biomarkers of stress and inflammation. Despite the numerous citations of the role of sleep in restoration and health maintenance, a paucity of research exists about this phenomenon in patients undergoing CPB. Specifically, there is no research that has explored correlations between sleep patterns and systemic inflammatory response in adult cardiac surgery patients. Exploratory, repeated-measures, correlational study. Subjects were recruited from a Midwestern urban hospital. Of the 25 eligible subjects, 16 males and four females completed the study. Wrist actigraphy was used to measure sleep variables. Salivary cortisol and C-reactive protein (C-RP) levels were measured daily. Data were collected during postoperative nights/days 1 through 4 (T1-T4). Subjects' sleep onset latency (SOL) median scores (0 minute) were within normal range across time periods, whereas median scores for wake after sleep onset (WASO > 270 minutes), sleep fragmentation index (SFI >51%), total sleep time (<153 minutes) and sleep efficiency index (SEI <36%) fell outside the normal ranges. Changes in the median sleep scores over time, however, were not significant at p > 0·05. Median cortisol levels were within normal range (0·3-0·8 μg/dl) from T1-T4, but the C-RP level peaked at T2 (median = 2370 pg/ml). Strong correlations were found: (1) between SFI-cortisol (rs = 0·82), C-RP (rs = 0·65) - WBC (rs = 0·69); (2) between SEI-C-RP (rs = 0·58); (3) between WASO-WBC (rs = 0·48), WASO and cross-clamp time (rs = 0·50); and (4) between SOL-age (rs = -0·55) at p < 0·05. Subjects were severely sleep-deprived with inflammatory response exaggerations warranting further investigations using larger sample sizes. This study offers a foundation for developing a conceptual model explaining mechanisms of sleep disturbance and inflammatory response postCPB. This knowledge is crucial for testing sleep-promoting interventions to modulate inflammatory responses essential for preventing complications, and restoring health.


Renal Stone Characterization using High Resolution Imaging Mode on a Photon Counting Detector CT System.
In addition to the standard-resolution (SR) acquisition mode, a high-resolution (HR) mode is available on a research photon-counting-detector (PCD) whole-body CT system. In the HR mode each detector consists of a 2x2 array of 0.225 mm × 0.225 mm subpixel elements. This is in contrast to the SR mode that consists of a 4x4 array of the same sub-elements, and results in 0.25 mm isotropic resolution at iso-center for the HR mode. In this study, we quantified ex vivo the capabilities of the HR mode to characterize renal stones in terms of morphology and mineral composition. Forty pure stones - 10 uric acid (UA), 10 cystine (CYS), 10 calcium oxalate monohydrate (COM) and 10 apatite (APA) - and 14 mixed stones were placed in a 20 cm water phantom and scanned in HR mode, at radiation dose matched to that of routine dual-energy stone exams. Data from micro CT provided a reference for the quantification of morphology and mineral composition of the mixed stones. The area under the ROC curve was 1.0 for discriminating UA from CYS, 0.89 for CYS vs COM and 0.84 for COM vs APA. The root mean square error (RMSE) of the percent UA in mixed stones was 11.0% with a medium-sharp kernel and 15.6% with the sharpest kernel. The HR showed qualitatively accurate characterization of stone morphology relative to micro CT.


Taxonomy of psychrophilic strains of Bacillus.
The morphological and physiological characteristics of 20 isolates of psychrophilic Bacillus were compared with 29 strains representing nine species of mesophilic Bacillus and 2 strains of Sporosarcina ureae to determine the taxonomic position of the psychrophiles. The psychrophiles formed four distinct groups which were sufficiently different from the mesophiles to warrant their designation as new species of Bacillus. The names B. psychrosaccharolyticus, B. insolitus, B. globisporus, and B. psychrophilus are proposed for the new species.


One-year psychophysical evaluation of COVID-19-induced olfactory disorders: a prospective cohort study.
Olfactory disorders are common in COVID-19. While many patients recover within weeks, a notable number of patients suffer from prolonged olfactory disorders. Much research has focused on the acute phase of olfactory disorders in COVID-19; however, there is still inconsistency regarding the prognosis. We aim to assess both objective and subjective olfactory function in patients with persisting olfactory disorders following COVID-19, 1 year after diagnosis. We objectively measured olfactory function in 77 patients who initially had COVID-19-induced smell disorders, 1 year after confirmed diagnosis. These patients previously underwent two objective measurements at approximately 3 and 6 months after COVID-19, in the context of the COCOS trial (COrticosteroids for COvid-19-induced loss of Smell). The main outcome measurement was TDI score (threshold-discrimination-identification) on Sniffin' Sticks Test (SST). Secondary outcomes included objective gustatory function on Taste Strip Test (TST), self-reported olfactory, gustatory and trigeminal function on a visual analogue scale (VAS) and outcomes on questionnaires about quality of life, and nasal symptoms. The findings of this study show that 1 year following COVID-19, the median TDI score increased to 30.75 (IQR 27.38-33.5), regarded as normosmia. The median TDI score started at 21.25 (IQR 18.25-24.75) at baseline and increased to 27.5 (IQR 23.63-30.0) at 6 months following COVID-19. The increase of 9.5 points on the TDI score between baseline and 1 year after COVID-19 marks a clinically relevant improvement. Regarding the self-reported VAS score (1-10) on sense of smell, it increased from 1.2 (IQR 0.4-3.0) at baseline to 3.2 (IQR 1.4-6.0) at 6 months and further improved up to 6.1 (IQR 2.7-7.5) after 1 year. Objective gustatory function increased with 2 points on TST a year after diagnosis. Self-reported olfactory, gustatory, and trigeminal functions also improved over time, as did quality of life. Objective and self-reported olfactory function continued to improve 1 year after COVID-19. The median TDI score of 30.75 (IQR 27.38-33.5) is regarded as normosmia, which is a favorable outcome. However, the rate of improvement on TDI score reduces over time.


[Monitoring of canine leishmaniasis in northern Italy: an update from a scientific network].
Canine leishmaniasis (CanL) due to Leishmania infantum is a disease of great veterinary importance and a serious public health problem. In humans, L. infantum causes visceral (VL) and cutaneous leishmaniasis (CL) and the distribution of VL overlaps that of CanL. Currently, VL is considered by WHO as an emerging zoonosis in southern Europe. The dog is the only domestic reservoir of the infection and phlebotomine sandflies are the only proven vectors of leishmaniasis for dogs and humans. CanL is endemic in Italy, particularly in central and southern regions, including islands. Until 1983, all regions of northern Italy but Liguria and some territories of Emilia Romagna were considered free from CanL. From early '90s new stable foci of CanL have appeared, most of them located within classical endemic areas including territories of Emilia Romagna, Tuscany, Umbria, Marche, and Abruzzi regions. But the most relevant aspect, from an epidemiological point of view, has been the appearance of stable CanL foci in northern Italy, namely in Veneto and Piedmont regions. In these two foci, entomological surveys showed the presence of P. perniciosus and of a second phlebotomine vector, P. neglectus, which may have played a role in the CanL diffusion in some parts of northern Italy. Furthermore, in these areas, autochthonous human VL cases have occurred. There is therefore a realistic risk that CanL infection could rapidly spread through northern latitudes and a surveillance activity is strongly needed. For this reason, in October 2002, thanks to the collaboration and support of Intervet Italia, the network "LeishMap" was created, with the main purpose of monitoring the spread of CanL and vectors in northern Italy. LeishMap consists of scientific and sanitary institutions with proven experience both in field surveys and diagnostic methodologies on CanL and phlebotomine vector. It is organised in 4 Operational Units (OU), represented by researchers of the Veterinary Faculties of the University of Bologna, Padua, Milan and Turin, under the scientific coordination of the MIPI Department, ISS of Rome and with the collaboration of private and public veterinarians operating in the regions under study. During the first year of activity, each OU was involved in the serological and entomological surveillance of several territories in the respective regions, where recent autochthonous CanL cases were registered. The studies have involved five regions, namely Valle D'Aosta, Piedmont, Lombardia, Veneto, Trentino-Alto Adige and Emilia Romagna. In the Symposium 6 of this Congress we report detailed results of a retrospective analysis of data concerning CanL and vectors in northern Italy till 2002 and the preliminary results of 2003 on the seroprevalence rates observed in foci studied and on the entomological surveys carried out. In summary, the results outlined that already known foci of CanL are expanding from the original sites. Several new foci have been identified and many others are at high risk of evolving toward a stable endemicity. P. perniciosus has been found in all but one the suspected new foci. In Emilia Romagna region P. perfiliewi was identified in 2 areas and in one was the only species present. The occurrence of P. neglectus was confirmed in three regions, Veneto, Lombardia and Piedmont. In conclusion, from the 2002-2003 LeishMap activities it appears that further monitoring activities are necessary to identify new endemic foci of CanL, this representing the prerequisite for the implementation of programs for leishmaniasis control in northern Italy.


Plasma catecholamines and the counterregulatory responses to hypoglycemia in infants: a critical role for epinephrine and cortisol.
The purpose of this study was to define plasma catecholamine responses as part of the counterregulatory hormonal reaction to hypoglycemia in infants after a regular 3- to 4-h feed was omitted. Hormone levels were assessed once, at the end of the fast or at hypoglycemia. The 121 infants were subdivided into three groups for analysis: normoglycemia (n = 94, 78%); transient hypoglycemia (n = 11, 9%); or severe and persistent hypoglycemia (n = 16, 13%). The severe and persistent hypoglycemic group had significantly higher levels of cortisol and epinephrine than the normoglycemic group. Norepinephrine and glucagon levels did not differ between the groups. Human GH levels were higher in the transiently hypoglycemic group but not in the severe and persistent hypoglycemic group. Prefeed blood lactate levels differed significantly among the groups and were highest in the severe and persistent groups. Multiple regression analysis showed that cortisol levels were significantly higher in infants who had severe and persistent hypoglycemia. The counterregulatory hormonal response in infants to severe and persistent hypoglycemia was limited to elevations in only cortisol and epinephrine levels but did not involve glucagon or human GH. This limited hormonal response may also contribute to the frequent occurrence of hypoglycemia in these infants.


Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review.
Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS. We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] -3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5-48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6-68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%-47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03-10.37]). Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS.


Treatment options for von Hippel-Lindau's haemangioblastomatosis: the role of gamma knife stereotactic radiosurgery.
Haemangioblastomas secondary to von Hippel-Lindau (VHL) disease can be difficult to manage surgically, which has lead to an interest in the use of stereotactic radiosurgery. Retrospectively reviewed here are 30 tumours treated in 14 patients with a mean +/- SD follow-up of 34 +/- 24 months. During this time, three of the 14 patients (21%) died, two of generalized progressive disease. Before radiosurgery, the median time between interventions for cranial haemangioblastomas was 3 years (mean 3.9 +/- 5.0 years). After radiosurgery, the tendency for cranial disease progression was similar, 50% of patients developing further disease by 5 years. Local tumour control was achieved in the majority of cases and estimates of this are included. Radiosurgery is a useful palliative measure controlling the majority of haemangioblastomas, although its efficacy in these patients is limited by the tendency of further disease to develop or progress intracranially.


The 48-hour exoerythrocytic stage of Plasmodium cynomolgi bastianellii.
Detection and specific identification of the 48-hour exoerythrocytic stage of the primate malaria parasite, Plasmodium cynomolgi bastianellii, was accomplished by means of a highly specific indirect immunofluorescence technique (IFA) applied to hepatic tissue fixed in Carnoy's solution. The 48-hour forms appeared as round-to-slightly-oval bodies of average mean diameter 3.0 micrometers (9 parasites) and lying with the cytoplasm of individual hepatic parenchymal cells; each possessed one to three non-fluorescent nuclei or nuclear sections (mean 1.6) within the brightly fluorescent parasitic cytoplasm. In contrast, 72-hour parasites (6) had an average mean diameter of 4.0 micrometers and a mean of 2.2 nuclei. Restaining of IFA preparations with the Giemsa-colophonium method confirmed the plasmodial nature of fluorescent forms, despite some modification of staining characteristics produced by the prolonged exposure of sections to the aqueous phase of the IFA procedure. Exoerythrocytic forms could not be detected in biopsies obtained 24 hours following sporozoite inoculation.


HIV care for geographically mobile populations.
The interaction between geographic mobility and risk for human immunodeficiency virus infection is well recognized, but what happens to those same individuals, once infected, as they transition to living with the infection? Does mobility affect their transition into medical care? If so, do mobile and nonmobile populations achieve similar success with antiretroviral treatment? The definition of mobility has changed over the centuries to encompass a complex phenotype including permanent migration, frequent travel, circular migration, and travel to and from treatment centers. The heterogeneity of these definitions leads to discordant findings. Investigations show that mobility has an impact on infection risk, but fewer data exist on the impact of geographic mobility on medical care and treatment outcomes. This review will examine existing data regarding the impact of geographic mobility on access to and maintenance in medical care and on adherence to antiretroviral therapy for those living with human immunodeficiency virus infection. It will also expand the concept of mobility to include data on the impact of the distance from residence to clinic on medical care and treatment adherence. Our conclusions are that the existing literature is limited by varying definitions of mobility and the inherent oversimplification necessary to apply a "mobility measure" in a statistical analysis. The impact of mobility on antiretroviral treatment outcomes deserves further exploration to both define the phenomenon and target interventions to these at-risk populations.


Biomolecular cytokine therapy.
As for the chronicity of inflammatory-immune diseases, the medication of them needs to be longterm and thus, quite safe with respect to side effects due to drug actions. Therapy of these diseases includes steroid and non steroid anti-inflammatories given in monotherapy or in combination with cytotoxic antimetabolites. Longterm administration of these active substances cumulate in side effects, not to speak of the probability of developing unresponsiveness to the drug in use. In principle, the earlier the intervention, the better the outcome of medication in therapy. In harmony with this principle, biopharmacology focuses on specific targets in early (acute) phase of inflammatory-immune diseases. One of these targets is the proinflammatory cascade of cytokines (IL1beta, IL6, IL8, IL12, TNFalpha). Among them, the overproduction of tumor necrosis factor (TNFalpha) is suggested to orchestrate and escalate the disease phenotype. Hence, targeting of TNFa may restrict or stop the propagation of pathological reactions. TNFalpha in its excess can be captured at transcription, translation, secretion levels as well as in the extracellular soluble form. This latter approach is supported by clinical records emphasizing the use of recombinant antibodies and soluble receptors in trapping extra amounts of TNFalpha. This review serves as an illustration for the efficacy and safety of infliximab (antibody) and etanercept (soluble receptor) in the example of rheumatoid arthritis (RA).


Weight control belief and its impact on the effectiveness of tobacco control policies on quit attempts: findings from the ITC 4 Country Survey.
Weight concerns are widely documented as one of the major barriers for girls and young adult women to quit smoking. Therefore, it is important to investigate whether smokers who have weight concerns respond to tobacco control policies differently than smokers who do not in terms of quit attempts, and how this difference varies by gender and country. This study aims to investigate, by gender and country, whether smokers who believe that smoking helps control weight are less responsive to tobacco control policies with regards to quit attempts than those who do not. We use longitudinal data from the International Tobacco Control Policy Evaluation Project in the USA, Canada, the UK and Australia to conduct the analysis. We first constructed a dichotomous indicator for smokers who have the weight control belief and then examined the disparity in policy responsiveness in terms of quit attempts by directly estimating the interaction terms of policies and the weight control belief indicator using generalised estimating equations. We find that weight control belief significantly attenuates the policy impact of tobacco control measures on quit attempts among US female smokers and among UK smokers. This pattern was not found among smokers in Canada and Australia. Although our results vary by gender and country, the findings suggest that weight concerns do alter policy responsiveness in quit attempts in certain populations. Policy makers should take this into account and alleviate weight concerns to enhance the effectiveness of existing tobacco control policies on promoting quitting smoking.


Facilitating international medical graduates' acculturation: From theory to practice.
International medical graduates (IMGs) are forming an ever-increasing proportion of the medical workforce. Much of the discourse around IMGs is about their performance at work and interventions to improve it. This discourse, however, is rarely situated in the wider context of the experiences of IMGs as migrants despite the wider context of migration and acculturation being likely to have a significant impact on IMGs' well-being and, ultimately, performance at work. The objectives of this article were to (1) raise awareness of the inextricable broader context within which IMGs are situated as migrants; (2) outline the impact this context might have on IMGs' performance; (3) discuss literature from the social sciences related to acculturation that could better inform the way we view IMG transition and performance; (4) highlight how acculturation theory can help inform the design, implementation and evaluation of interventions to facilitate the transition of IMGs into the host country and the workplace; (5) list some interventions that can provide support; and (6) suggest theory driven lines of enquiry to study acculturation in IMGs and the impact related issues might have on performance. This is a cross-cutting edge review drawing on selected theory and literature from the social sciences to explore its relevance to IMGs. The broader context of migration and acculturation should not be ignored when discussing IMG performance in the workplace or when instigating interventions to improve it. There is an urgent need to further evaluate the impact this broader context has on IMGs' well-being and performance.


A continuous-time Markov model approach for modeling myelodysplastic syndromes progression from cross-sectional data.
The integration of both genomics and clinical data to model disease progression is now possible, thanks to the increasing availability of molecular patients' profiles. This may lead to the definition of novel decision support tools, able to tailor therapeutic interventions on the basis of a "precise" patients' risk stratification, given their health status evolution. However, longitudinal analysis requires long-term data collection and curation, which can be time demanding, expensive and sometimes unfeasible. Here we present a clinical decision support framework that combines the simulation of disease progression from cross-sectional data with a Markov model that exploits continuous-time transition probabilities derived from Cox regression. Trajectories between patients at different disease stages are stochastically built according to a measure of patient similarity, computed with a matrix tri-factorization technique. Such trajectories are seen as realizations drawn from the stochastic process driving the transitions between the disease stages. Eventually, Markov models applied to the resulting longitudinal dataset highlight potentially relevant clinical information. We applied our method to cross-sectional genomic and clinical data from a cohort of Myelodysplastic syndromes (MDS) patients. MDS are heterogeneous clonal hematopoietic disorders whose patients are characterized by different risks of Acute Myeloid Leukemia (AML) development, defined by an international score. We computed patients' trajectories across increasing and subsequent levels of risk of developing AML, and we applied a Cox model to the simulated longitudinal dataset to assess whether genomic characteristics could be associated with a higher or lower probability of disease progression. We then used the learned parameters of such Cox model to calculate the transition probabilities of a continuous-time Markov model that describes the patients' evolution across stages. Our results are in most cases confirmed by previous studies, thus demonstrating that simulated longitudinal data represent a valuable resource to investigate disease progression of MDS patients.


The complete mitochondrial genome of the epiphytic moss Orthotrichum speciosum.
The mitogenome of the Orthotrichum speciousum (GenBank accession number KM288416) has a total length of 104,747 bp and consist of 40 protein-coding genes, 3 ribosomal RNA (rRNA) and 24 transfer RNA. The gene order is identical to other known moss mitogenomes.


Improving chronic disease prevention and screening in primary care: results of the BETTER pragmatic cluster randomized controlled trial.
Primary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system. However, there remains a gap between recommended preventive services and actual practice. This trial (the BETTER Trial) aimed to improve preventive care of heart disease, diabetes, colorectal, breast and cervical cancers, and relevant lifestyle factors through a practice facilitation intervention set in primary care. Pragmatic two-way factorial cluster RCT with Primary Care Physicians' practices as the unit of allocation and individual patients as the unit of analysis. The setting was urban Primary Care Team practices in two Canadian provinces. Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control; 4 physicians in each team (32 physicians) were randomly assigned to receive the patient-level intervention or wait-list control. Patients randomly selected from physicians' rosters were stratified into two groups: 1) general and 2) moderate mental illness. The interventions involved a multifaceted, evidence-based, tailored practice-level intervention with a Practice Facilitator, and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored 'prevention prescription'. The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets, expressed as the ratio of eligible actions at baseline that were met at follow-up. A cost-effectiveness analysis was conducted. 789 of 1,260 (63%) eligible patients participated. On average, patients were eligible for 8.96 (SD 3.2) actions at baseline. In the adjusted analysis, control patients met 23.1% (95% CI: 19.2% to 27.1%) of target actions, compared to 28.5% (95% CI: 20.9% to 36.0%) receiving the practice-level intervention, 55.6% (95% CI: 49.0% to 62.1%) receiving the patient-level intervention, and 58.9% (95% CI: 54.7% to 63.1%) receiving both practice- and patient-level interventions (patient-level intervention versus control, P < 0.001). The benefit of the patient-level intervention was seen in both strata. The extra cost of the intervention was $26.43CAN (95% CI: $16 to $44) per additional action met. A Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner.


Prevalence of winter migration to warmer destinations among Ontarians ("snowbirds") and patterns of their use of health care services: a population-based analysis.
Older Canadians frequently migrate to warmer destinations for the winter season (snowbirds). Our aim was to examine the prevalence of migration to warmer destinations among Ontarians, and to compare the characteristics and use of health care services of snowbirds to those of older Ontarians who did not migrate for the winter. We conducted a population-based analysis using health administrative databases from Ontario. We compiled 10 seasonal cohorts (2009/10 to 2018/19) of adults aged 65 or more who filled a travel supply of medications under the Ontario Drug Benefits program (snowbirds) between September and January (snowbird season). We calculated the seasonal prevalence of snowbirds per 100 Ontarians aged 65 or more. We matched each snowbird in the 2018/19 season to 2 nonsnowbirds on age and sex, and compared their characteristics and patterns of use of government-funded health care services. Over the 10-year period, 53 431 to 70 863 Ontarians aged 65 or more were identified as snowbirds (seasonal prevalence 2.6%-3.3%). Compared to nonsnowbirds, snowbirds were more likely to be recent migrants, live in higher-income neighbourhoods, have fewer comorbidities and make more visits to primary care physicians. From January to March 2019, snowbirds accessed government-funded health care services for a median of 0 days (interquartile range [IQR] 0-1 d), compared to 4 days (IQR 2-8 d) among nonsnowbirds. About 3% of older Ontarians migrate to warmer destinations for the winter each season. Since few access health care services in Ontario from January to March, researchers are encouraged to consider the snowbird population and the impact of their absence on evaluations that assume continuous observation.


Brevundimonas vesicularis (S1T13) Mitigates Drought-Stress-Associated Damage in Arabidopsis thaliana.
Drought stress is a significant threat to agricultural productivity and poses challenges to plant survival and growth. Research into microbial plant biostimulants faces difficulties in understanding complicated ecological dynamics, molecular mechanisms, and specificity; to address these knowledge gaps, collaborative efforts and innovative strategies are needed. In the present study, we investigated the potential role of Brevundimonas vesicularis (S1T13) as a microbial plant biostimulant to enhance drought tolerance in Arabidopsis thaliana. We assessed the impact of S1T13 on Col-0 wild-type (WT) and atnced3 mutant plants under drought conditions. Our results revealed that the inoculation of S1T13 significantly contributed to plant vigor, with notable improvements observed in both genotypes. To elucidate the underlying mechanisms, we studied the role of ROS and their regulation by antioxidant genes and enzymes in plants inoculated with S1T13. Interestingly, the inoculation of S1T13 enhanced the activities of GSH, SOD, POD, and PPO by 33, 35, 41, and 44% in WT and 24, 22, 26, and 33% in atnced3, respectively. In addition, S1T13 upregulated the expression of antioxidant genes. This enhanced antioxidant machinery played a crucial role in neutralizing ROS and protecting plant cells from oxidative damage during drought stress. Furthermore, we investigated the impact of S1T13 on ABA and drought-stress-responsive genes. Similarly, S1T13 modulated the production of ABA and expression of AO3, ABA3, DREB1A, and DREB2A by 31, 42, 37, 41, and 42% in WT and 20, 29, 27, 38, and 29% in atnced3. The improvement in plant vigor, coupled with the induction of the antioxidant system and modulation of ABA, indicates the pivotal role of S1T13 in enhancing the drought stress tolerance of the plants. Conclusively, the current study provides valuable insights for the application of multitrait S1T13 as a novel strain to improve drought stress tolerance in plants and could be added to the consortium of biofertilizers.


White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats.
Agaricus bisporus (white button mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B(12); folates; and polyphenols that may provide beneficial effects on cardiovascular and diabetic diseases. The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates anticholesterolemic and antiglycemic responses in rats fed a hypercholesterolemic diet (0.5% cholesterol; 14% fat) and rats with type 2 diabetes induced by injection of streptozotocin (STZ) (50 mg/kg body weight), respectively. The STZ-induced diabetic male Sprague-Dawley rats fed the Agaricus bisporus powder (ABP; 200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride (TG) concentrations (24.7% and 39.1%, respectively), liver enzyme activities, alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%, respectively), and liver weight gain (P < .05). In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma total cholesterol (TC) and low-density lipoprotein (LDL) (22.8% and 33.1%, respectively) (P < .05). A similar significant decrease in hepatic cholesterol and TG concentrations was observed (36.2% and 20.8%, respectively) (P < .05). Decrease in TC, LDL, and TG concentrations was accompanied by a significant increase in plasma high-density lipoprotein concentrations. It was concluded that A bisporus mushroom had both hypoglycemic and hypolipidemic activity in rats.


Effect of calcitonin on urine concentration in the rat.
Because mammalian distal nephron segments with both calcitonin- and antidiuretic hormone- (ADH) sensitive adenylate cyclase activity have been described, in vivo and in vitro experiments were performed to study the effect of calcitonin on rat distal nephron water permeability. Calcitonin 1 and 0.1 U/ml, but not 0.01 U/ml, significantly increased the diffusional water permeability in the isolated papillary collecting duct by 15 and 11%, respectively. However, this effect was small when compared with a 68% increase with a supramaximal concentration of ADH (from 4.0 +/- 0.3 to 6.7 +/- 0.9 microns/s; n = 6, P less than 0.01). The normal increase in water permeability with increasing concentration of ADH (0.02 and 0.2 mU/ml) was depressed by the previous addition of calcitonin (1 U/ml) to the bath but was unaltered with the supramaximal ADH concentration (2 mU/ml). Verapamil, a compound that antagonizes cellular calcium entry, did not alter the effect of calcitonin on diffusional water permeability. Calcitonin in concentrations of 0.05, 0.5, and 5 U/ml produced a significant reduction in urine flow and free water clearance. Pretreatment with calcitonin in these concentrations inhibited the antidiuretic action of ADH. These studies suggest that calcitonin acts as a partial agonist to ADH within the distal nephron. It is unclear whether such an action represents a physiological or a pharmacological effect.


Purification, characterization, and physiological function of Bacillus subtilis ornithine transcarbamylase.
A procedure was developed for purification of ornithine transcarbamylase (OTCase) to near homogeneity from Bacillus subtilis 168. The purified native enzyme existed as a mixture of dimeric, tetrameric, and hexameric forms, but was converted to the dimer in the presence of 2-mercaptoethanol. The molecular weight of the subunit was 44,000. Some general kinetic properties of the enzyme were described. OTCase was repressed by arginine in growing B. subtilis cells, but the enzyme was induced by arginine at the end of exponential growth. Specific antibodies against the purified OTCase were used to show that the same enzyme was produced under all conditions. These results and studies of a mutant lacking OTCase demonstrated that B. subtilis produced only a single OTCase. OTCase was clearly required for arginine biosynthesis, but the physiological function of OTCase induction by arginine was obscure. OTCase was not induced by, or required for, growth on arginine as a carbon and nitrogen source. Absence of OTCase in a mutant did not alter the yield or arginine content of its spores in comparison to a strain containing OTCase.


Cytoskeletal matrix in striated muscle: the role of titin, nebulin and intermediate filaments.
In this chapter, first I will briefly describe the molecular properties of titin and nebulin --two extremely large, myofibrillar proteins--and discuss their distribution and organization in the sarcomere. Although these novel proteins are major myofibrillar components of a wide range of striated muscles, they have escaped the attention of muscle biochemists until very recently. As I shall point out below, biochemical studies of these proteins have been unexpectedly challenging; many standard techniques had to be modified before they became capable of handling such giant proteins. In addition, our structural studies of these proteins have encountered a challange of a different nature: how to explain their distribution in the sarcomere according to the currently accepted two filament sarcomere model, because these proteins do not appear to be thick or thin filament-associated regulatory or anchoring proteins. These studies have led us to reexamine the question of whether continuous, longitudinal filaments exist within the sarcomere of striated muscle. I will attempt to integrate our results, as well as available literature data, within the framework of a hypothetical sarcomere model which incorporates an elastic filamentous matrix consisting of titin and nebulin as additional sarcomere constituents. Finally, I will very briefly mention our recent findings that an extensive three dimensional network of intermediate (10 nm) filaments, distinct from titin and nebulin , is intimately associated with the sarcomere of adult striated muscle. I believe that the recognition of the existence of two sets of sarcomere-associated cytoskeletal filaments within adult striated muscle fibers may be a significant step toward resolving some of the unsettled questions in muscle mechanics such as those that have been discussed in this meeting.


Σ-holes, π-holes and electrostatically-driven interactions.
A positive π-hole is a region of positive electrostatic potential that is perpendicular to a portion of a molecular framework. It is the counterpart of a σ-hole, which is along the extension of a covalent bond to an atom. Both σ-holes and π-holes become more positive (a) in going from the lighter to the heavier atoms in a given Group of the periodic table, and (b) as the remainder of the molecule is more electron-withdrawing. Positive σ- and π-holes can interact in a highly directional manner with negative sites, e.g., the lone pairs of Lewis bases. In this work, the complexes of 13 π-hole-containing molecules with the nitrogen lone pairs of HCN and NH(3) have been characterized computationally using the MP2, M06-2X and B3PW91 procedures. While the electrostatic interaction is a major driving force in π-hole bonding, a gradation is found from weakly noncovalent to considerably stronger with possible indications of some degree of coordinate covalency.


Acupuncture Improves Comorbid Cognitive Impairments Induced by Neuropathic Pain in Mice.
Growing evidence indicates that neuropathic pain is frequently accompanied by cognitive impairments, which aggravate the quality of life of chronic pain patients. Here, we investigated whether acupuncture treatments can improve cognitive dysfunction as well as allodynia induced by neuropathic pain in mice. One week after the left partial sciatic nerve ligation (PSNL), acupuncture treatments on the acupoints GB30-GB34 (AP1), HT7-GV20 (AP2), or control points (CP) were performed for 4 weeks. Notably, the significant attenuations of mechanical allodynia and cognitive impairment were observed in the AP1 group, but not in PSNL, AP2, or CP groups. A random decision forest classifier based on the pain and cognitive functions displayed that the acupuncture group was clearly segregated from the other groups. We also demonstrated that acupuncture restored the reduced field excitatory post-synaptic potentials and was able to elevate the expression levels of glutamate receptors (NR2B and GluR1) in the hippocampus. Moreover, the expressions of Ca2+/calmodulin-dependent protein kinase II and synaptic proteins (pPSD-95 and pSyn-1) were enhanced by acupuncture treatment. These results suggest that acupuncture can enhance hippocampal long-term action through the regulation of the synaptic efficacy and that acupuncture may provide a viable option for managing both pain and cognitive functions associated with chronic neuropathic pain.


Using Papaverine and Its Metabolites, 6-Desmethyl Papaverine and 4',6-Didesmethyl Papaverine as Biomarkers to Improve the Detection Time of Heroin Use.
Opioid usage in the USA has increased over the past decade, with prescriptions increasing from 76 million in 1991 to 207 million in 2013. New regulations have curbed the number of prescriptions, leading to an increase in heroin use. Heroin-related overdoses have quadrupled between 2000 and 2015. The traditional urinary biomarkers for indicating heroin use are a combination of morphine and 6-acetyl morphine (6-AM). Morphine is detectable in urine for several days. 6-AM is detected in urine for 2-8 hours. Papaverine has been proposed as an alternative heroin biomarker. It has been reported to have a 1-2 day detection window. Papaverine metabolites have been reported to have up to a 3-day detection window. Presented is a method for the detection of papaverine and its metabolites, 6-desmethyl papaverine (6-DMP) and 4', 6-didesmethyl papaverine (4,6-DDMP), in urine using a modified Waters® MCX™ microelution method. An ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS), with a Waters' BEH C18 column, and 20 mM ammonium formate water: 20 mM ammonium formate methanol mobile phase was employed. Calibration curves were linear from 0.1 to 50 ng/mL. No interferences were observed from the analysis of multicomponent therapeutic drug or drugs of abuse control materials; intra- and inter-run precision tests were acceptable. A total of 428 genuine urine specimens where heroin use was suspected were analyzed. These included 101 6-AM and 179 morphine only positive samples as well as 6 morphine-negative samples where papaverine and/or metabolites were detected. The determined concentrations in these samples for papaverine, 6-DMP and 4,6-DDMP ranged from 0.10 to 994, 0.10 to 462 and 0.12 to 218 ng/mL, respectively. The method was rugged and robust for the analysis of papaverine and metabolites, 6-DMP and 4,6-DDMP. The use papaverine and metabolites, 6-DMP and 4,6-DDMP has the potential to increase the detection window of heroin use.


Effects of Muscle Strength Training on Muscle Mass Gain and Hypertrophy in Older Adults With Osteoarthritis: A Systematic Review and Meta-Analysis.
To investigate the effect of muscle strength exercise training (MSET) on lean mass (LM) gain and muscle hypertrophy in older patients with lower extremity osteoarthritis (OA). A comprehensive search of online databases was performed on April 20, 2019. Randomized controlled trials (RCTs) that reported the effects of MSET on LM, muscle thickness, and cross-sectional area (CSA) in older patients with OA were identified. A risk of bias assessment and meta-analysis were performed for the included RCTs. We included 19 RCTs with a median Physiotherapy Evidence Database score of 6 of 10 (range 3-7). In total, data from 1,195 patients (65% women, 85% with knee OA) with a mean age of 62.1 years (range 40-86 years) were analyzed. MSET resulted in significantly higher LM gain (standardized mean difference [SMD] 0.49 [95% confidence interval (95% CI) 0.28, 0.71], P < 0.00001) than did the nonexercise controls. Meta-analysis results revealed significantly positive effects of MSET on muscle thickness (SMD 0.82 [95% CI 0.20, 1.43], P = 0.009) and CSA (SMD 0.80 [95% CI 0.25, 1.35], P = 0.004) compared with nonexercise controls. No significant effects in favor of MSET were observed for any muscle outcome compared with exercise controls. Five RCTs reported nonsevere adverse events in response to MSET, whereas no RCTs reported severe events. MSET is effective in increasing LM and muscle size in older adults with OA. Clinicians should incorporate MSET into their management of patients at risk of low muscle mass to maximize health status, particularly for older individuals with OA.


The Development and Preliminary Validation of a Rubric to Assess Medical Students' Written Summary Statements in Virtual Patient Cases.
The ability to create a concise summary statement can be assessed as a marker for clinical reasoning. The authors describe the development and preliminary validation of a rubric to assess such summary statements. Between November 2011 and June 2014, four researchers independently coded 50 summary statements randomly selected from a large database of medical students' summary statements in virtual patient cases to each create an assessment rubric. Through an iterative process, they created a consensus assessment rubric and applied it to 60 additional summary statements. Cronbach alpha calculations determined the internal consistency of the rubric components, intraclass correlation coefficient (ICC) calculations determined the interrater agreement, and Spearman rank-order correlations determined the correlations between rubric components. Researchers' comments describing their individual rating approaches were analyzed using content analysis. The final rubric included five components: factual accuracy, appropriate narrowing of the differential diagnosis, transformation of information, use of semantic qualifiers, and a global rating. Internal consistency was acceptable (Cronbach alpha 0.771). Interrater reliability for the entire rubric was acceptable (ICC 0.891; 95% confidence interval 0.859-0.917). Spearman calculations revealed a range of correlations across cases. Content analysis of the researchers' comments indicated differences in their application of the assessment rubric. This rubric has potential as a tool for feedback and assessment. Opportunities for future study include establishing interrater reliability with other raters and on different cases, designing training for raters to use the tool, and assessing how feedback using this rubric affects students' clinical reasoning skills.


Benefits of acupuncture for diabetic gastroparesis: a comparative preliminary study.
The aim of this preliminary study was to compare the effectiveness of domperidone and acupuncture for the management of diabetic gastroparesis. This was a preliminary, prospective non-randomised, unblinded case-crossover study conducted in patients with longstanding, uncontrolled diabetes mellitus and gastroparesis. All patients received domperidone (20 mg four times a day) for 12 weeks, followed by a 2-3 week washout period, and then biweekly acupuncture treatments for 8 weeks. Gastric emptying rate, glucose and glycated haemoglobin (HbA1C) levels were measured at start and end of each treatment period. At each of these timepoints patients completed the Gastroparesis Cardinal Symptom Index (GCSI), the Satisfaction with Life Scale (SWLS), and the Short-Form 36 Health Survey Update (SF-36). The trial was curtailed after only eight participants could be recruited in 3 years. The mean age of patients was 57.1±9.9 years, the male:female ratio was 1:7 and mean body mass index (kg/m(2)) was 25.2±1.2. There was no change in any of the outcome parameters after treatment with domperidone. Acupuncture was associated with a decrease in scores for almost all cardinal symptoms of the GCSI, as well as in increased total score on the SWLS (p=0.002) and the social functioning domain of the SF-36 (p=0.054). Acupuncture did not lead to an improvement in gastric emptying, or glucose control from baseline. Acupuncture treatment may lead to symptomatic improvement in patients with diabetic gastroparesis. Within the limitations of this preliminary, non-randomised and unblinded study, it appears that this effect may be due to non-specific mechanisms.


Induction of linear tracks of DNA double-strand breaks by alpha-particle irradiation of cells.
Understanding how cells maintain genome integrity when challenged with DNA double-strand breaks (DSBs) is of major importance, particularly since the discovery of multiple links of DSBs with genome instability and cancer-predisposition disorders. Ionizing radiation is the agent of choice to produce DSBs in cells; however, targeting DSBs and monitoring changes in their position over time can be difficult. Here we describe a procedure for induction of easily recognizable linear arrays of DSBs in nuclei of adherent eukaryotic cells by exposing the cells to alpha particles from a small Americium source (Box 1). Each alpha particle traversing the cell nucleus induces a linear array of DSBs, typically 10-20 DSBs per 10 mum track length. Because alpha particles cannot penetrate cell-culture plastic or coverslips, it is necessary to irradiate cells through a Mylar membrane. We describe setup and irradiation procedures for two types of experiments: immunodetection of DSB response proteins in fixed cells grown in Mylar-bottom culture dishes (Option A) and detection of fluorescently labeled DSB-response proteins in living cells irradiated through a Mylar membrane placed on top of the cells (Option B). Using immunodetection, recruitment of repair proteins to individual DSB sites as early as 30 s after irradiation can be detected. Furthermore, combined with fluorescence live-cell microscopy of fluorescently tagged DSB-response proteins, this technique allows spatiotemporal analysis of the DSB repair response in living cells. Although the procedures might seem a bit intimidating, in our experience, once the source and the setup are ready, it is easy to obtain results. Because the live-cell procedure requires more hands-on experience, we recommend starting with the fixed-cell application.


Involvement of the ligninolytic system of white-rot and litter-decomposing fungi in the degradation of polycyclic aromatic hydrocarbons.
Polycyclic aromatic hydrocarbons (PAHs) are natural and anthropogenic aromatic hydrocarbons with two or more fused benzene rings. Because of their ubiquitous occurrence, recalcitrance, bioaccumulation potential and carcinogenic activity, PAHs are a significant environmental concern. Ligninolytic fungi, such as Phanerochaete chrysosporium, Bjerkandera adusta, and Pleurotus ostreatus, have the capacity of PAH degradation. The enzymes involved in the degradation of PAHs are ligninolytic and include lignin peroxidase, versatile peroxidase, Mn-peroxidase, and laccase. This paper summarizes the data available on PAH degradation by fungi belonging to different ecophysiological groups (white-rot and litter-decomposing fungi) under submerged cultivation and during mycoremediation of PAH-contaminated soils. The role of the ligninolytic enzymes of these fungi in PAH degradation is discussed.


Domain redistribution within ergosterol-containing model membranes in the presence of the antimicrobial compound fengycin.
The cyclic lipopeptide fengycin, produced by Bacillus subtilis, exhibits its antimicrobial capabilities by altering the integrity of the cell membrane of plant pathogens. Previous work has correlated fengycin activity with membrane characteristics, such as sterol content. This work focused on the influence of fengycin on supported lipid bilayers containing varying levels of ergosterol. Total internal reflection fluorescence (TIRF) microscopy was used to visualize and distinguish ordered (Lβ/Lo) and disordered (Lα/Ld) domains in the model membranes following exposure to low (50 μg) and high (500 μg) fengycin doses. Application of an initial low dose of fengycin to 0% and 3% ergosterol-containing bilayers resulted in redistribution of Lα/Lβ and Lo/Ld domains, respectively, which the bilayers compensated and corrected for over time. These membranes were unable to tolerate a second 50 μg dose or a single high fengycin dose. The 6% ergosterol bilayers were able to tolerate sequential low doses of fengycin. Exposure of these bilayers to the high fengycin dose caused a decrease in the number of Lo domains, albeit less than that seen in the 0% and 3% ergosterol bilayers. Bilayers containing 12% ergosterol, exhibited the least amount of change after fengycin exposure. These were the only bilayer to exhibit an increase in area taken up by ordered domains. These results suggest fengycin may preferentially act on the Lβ or Lo phase, the area in which ergosterol resides. Bilayers containing low levels of ergosterol appear to be more sensitive to the lipopeptide, suggesting ergosterol plays a role in buffering perturbations caused by fengycin.


Endothelin-1 levels and conduit artery mechanical properties in end-stage renal disease.
Endothelial cell (EC) dysfunction markers are increased in end-stage renal disease (ESRD). The present study focused on the relationship between EC markers, conduit artery wall mechanics and hemodynamics in ESRD. In 29 ESRD patients and 16 controls, brachial artery diameter, distension, and wall thickness was measured and circumferential wall stress (CWS) calculated. Shear stress was determined with a shear rate-estimating system. Furthermore, von Willebrand factor antigen (vWF) and endothelin-1 (ET-1) levels were measured. vWF (p = 0.002) and ET-1 (p < 0.001) were higher in ESRD patients and vWF was related to ET-1 (r = 0.70, p = 0.005). Peak (p = 0.001) and mean shear stress (p = 0.003) were significantly lower in ESRD patients, and ET-1 showed an inverse log linear relation with both (peak: r = -0.59, p = 0.016; mean: r = -0.64, p = 0.007). Also, ET-1 was log linearly related to CWS (r = 0.58, p = 0.014). These results indicate that, in ESRD, conduit artery shear stress is lower, which might be secondary to an increased peripheral vascular resistance caused by higher ET-1 levels.


Body mass trajectories through adulthood: results from the National Longitudinal Survey of Youth 1979 Cohort (1981-2006).
Most studies describing change in body mass through adulthood model an 'average' trajectory bearing the same functional form in the underlying population. Latent-class growth modelling has revealed the presence of several underlying body mass/obesity trajectory groups among children and adolescents, but has not been applied to capture adult body mass trajectories. We apply the technique to identify adult body mass trajectory groups, risk factors for group membership and (time-varying) modifiers of trajectory level within each group, and assess association between group membership and important health outcomes in midlife. Body mass trajectory groups, from age 18 to 49 years, were identified using latent-class growth modelling based on the National Longitudinal Survey of Youth 1979 (n = 9681). Role of gender, race/ethnicity and age cohort as risk factors for group membership, and of highest grade of education completed, years of urban living, years in employment, years in poverty and years married as modifiers of trajectory level was evaluated. Four trajectory groups, 'normal weight', 'overweight', 'late adulthood obesity' and 'early adulthood obesity' were identified. Males, Blacks and those born later had higher odds of being in the three latter groups. More education and years married lowered the trajectory within each group. The prevalence of most health outcomes was lowest in the 'normal weight' group, somewhat greater in the 'overweight' group, greater again in the 'late adult obesity group' and highest in the 'early adulthood obesity' group. Regular body mass index screening and monitoring in early adult life may identify a person as belonging to one of these four groups early, and allow the individual and health-care providers opportunities to initiate behavioural or other interventions better tailored to the specific group.


Significant Facility-Level Variation in Utilization of and Adherence with Secondary Prevention Therapies Among Patients with Premature Atherosclerotic Cardiovascular Disease: Insights from the VITAL (Veterans wIth premaTure AtheroscLerosis) Registry7.
We investigated facility-level variation in the use and adherence with antiplatelets and statins among patients with premature and extremely premature ASCVD. Using the 2014-2015 nationwide Veterans wIth premaTure AtheroscLerosis (VITAL) registry, we assessed patients with premature (age at first ASCVD event: males < 55 years, females < 65 years) and extremely premature ASCVD (< 40 years). We examined frequency and facility-level variation in any statin, high-intensity statin (HIS), antiplatelet use (aspirin, clopidogrel, ticagrelor, prasugrel, and ticlopidine), and statin adherence (proportion of days covered ≥ 0.8) across 130 nationwide VA healthcare facilities. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of statins or antiplatelets and statin adherence. Our analysis included 135,703 and 7716 patients with premature and extremely premature ASCVD, respectively. Across all facilities, the median (IQR) prescription rate of any statin therapy, HIS therapy, and antiplatelets among patients with premature ASCVD was 0.73 (0.70-0.75), 0.36 (0.32-0.41), and 0.77 (0.73-0.81), respectively. MRR (95% CI) for any statin use, HIS use, and antiplatelet use were 1.53 (1.44-1.60), 1.58 (1.49-1.66), and 1.49 (1.42-1.56), respectively, showing 53, 58, and 49% facility-level variation. The median (IQR) facility-level rate of statin adherence was 0.58 (0.55-0.62) and MRR for statin adherence was 1.13 (1.10-1.15), showing 13% facility-level variation. Similar median facility-level rates and variation were observed among patients with extremely premature ASCVD. There is suboptimal use and significant facility-level variation in the use of statin and antiplatelet therapy among patients with premature and extremely premature ASCVD. Interventions are needed to optimize care and minimize variation among young ASCVD patients.


Mimicking a SURF1 allele reveals uncoupling of cytochrome c oxidase assembly from translational regulation in yeast.
Defects in mitochondrial energy metabolism lead to severe human disorders, mainly affecting tissues especially dependent on oxidative phosphorylation, such as muscle and brain. Leigh Syndrome describes a severe encephalomyopathy in infancy, frequently caused by mutations in SURF1. SURF1, termed Shy1 in Saccharomyces cerevisiae, is a conserved assembly factor for the terminal enzyme of the respiratory chain, cytochrome c oxidase. Although the molecular function of SURF1/Shy1 is still enigmatic, loss of function leads to cytochrome c oxidase deficiency and reduced expression of the central subunit Cox1 in yeast. Here, we provide insights into the molecular mechanisms leading to disease through missense mutations in codons of the most conserved amino acids in SURF1. Mutations affecting G(124) do not compromise import of the SURF1 precursor protein but lead to fast turnover of the mature protein within the mitochondria. Interestingly, an Y(274)D exchange neither affects stability nor localization of the protein. Instead, SURF1(Y274D) accumulates in a 200 kDa cytochrome c oxidase assembly intermediate. Using yeast as a model, we demonstrate that the corresponding Shy1(Y344D) is able to overcome the stage where cytochrome c oxidase assembly links to the feedback regulation of mitochondrial Cox1 expression. However, Shy1(Y344D) impairs the assembly at later steps, most apparent at low temperature and exhibits a dominant-negative phenotype upon overexpression. Thus, exchanging the conserved tyrosine (Y(344)) with aspartate in yeast uncouples translational regulation of Cox1 from cytochrome c oxidase assembly and provides evidence for the dual functionality of Shy1.


High-sensitivity cardiac troponin I and risk of heart failure in patients with suspected acute coronary syndrome: a cohort study.
Heart failure may occur following acute myocardial infarction, but with the use of high-sensitivity cardiac troponin assays we increasingly diagnose patients with minor myocardial injury. Whether troponin concentrations remain a useful predictor of heart failure in patients with acute coronary syndrome is uncertain. We identified all consecutive patients (n = 4748) with suspected acute coronary syndrome (61 ± 16 years, 57% male) presenting to three secondary and tertiary care hospitals. Cox-regression models were used to evaluate the association between high-sensitivity cardiac troponin I concentration and subsequent heart failure hospitalization. C-statistics were estimated to evaluate the predictive value of troponin for heart failure hospitalization. Over 2071 years of follow-up there were 83 heart failure hospitalizations. Patients with troponin concentrations above the upper reference limit (URL) were more likely to be hospitalized with heart failure than patients below the URL (118/1000 vs. 17/1000 person years, adjusted hazard ratio: 7.0). Among patients with troponin concentrations <URL the rate of heart failure hospitalization was 2.80-fold higher [95% confidence interval (95% CI 1.81-4.31)] per doubling of troponin concentration. On adding troponin to a model with demographic, cardiovascular risk factor, and clinical variables, the prediction of heart failure hospitalization improved considerably (C-statistic 0.80 vs. 0.86, P < 0.001). Cardiac troponin is an excellent predictor of heart failure hospitalization in patients with suspected acute coronary syndrome. The strongest associations were observed in patients with troponin concentrations in the normal reference range, in whom high-sensitivity cardiac troponin assays identify those at increased risk of heart failure who may benefit from further investigation and treatment.


Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation.
Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2. Temporal regulation by groups of transcription factors across developmental stages reveals that cellular reprogramming precedes the induction of neuronal programs. TFAP4 and ASCL1/2 feedback are identified as potential regulators of ASCL1 and ASCL2 expression. Our study provides temporal transcriptional patterns and uncovers pan-tissue parallels between prostate and lung cancers, as well as connections to normal neuroendocrine cell states.


A Pilot Study of a Behavioral Parent Training in the Republic of Macedonia.
Parenting children with autism in countries with limited professional and financial resources can be overwhelming. Parent training led by non-governmental organizations may help alleviate some of these burdens. The present pilot study was conducted in the Republic of Macedonia, a country located in Southeastern Europe. The purpose of the study was to evaluate a parent training model for disseminating evidence-based practices through didactic and pyramidal training strategies. Results indicated that children improved on a number of different behaviors and results provide some evidence that parenting confidence and distress improved.


Inactivation of olfactory sensilla of a single morphological type differentially affects the response of Drosophila to odors.
The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe. Our data suggest that BS are required for a normal sensitivity to many odorants with a variety of chemical structures, through a wide range of concentrations. Interestingly, however, in contrast to other odorants tested, the behavioral response of ablated flies to intermediate concentrations of propionic and butyric acids is normal, suggesting the involvement of sensilla unaffected by ectopic reaper expression, probably coeloconic sensilla that respond strongly to these two organic acids. As inactivation of BS causes an underestimation of the concentration of both acids detectable at both the highest and lowest odorants concentrations, our results suggest that concentration coding for these two odorants relies on the integration of signals from different subsets of sensilla, most likely of different morphological types.


Fast numerical methods for simulating large-scale integrate-and-fire neuronal networks.
We discuss numerical methods for simulating large-scale, integrate-and-fire (I&F) neuronal networks. Important elements in our numerical methods are (i) a neurophysiologically inspired integrating factor which casts the solution as a numerically tractable integral equation, and allows us to obtain stable and accurate individual neuronal trajectories (i.e., voltage and conductance time-courses) even when the I&F neuronal equations are stiff, such as in strongly fluctuating, high-conductance states; (ii) an iterated process of spike-spike corrections within groups of strongly coupled neurons to account for spike-spike interactions within a single large numerical time-step; and (iii) a clustering procedure of firing events in the network to take advantage of localized architectures, such as spatial scales of strong local interactions, which are often present in large-scale computational models-for example, those of the primary visual cortex. (We note that the spike-spike corrections in our methods are more involved than the correction of single neuron spike-time via a polynomial interpolation as in the modified Runge-Kutta methods commonly used in simulations of I&F neuronal networks.) Our methods can evolve networks with relatively strong local interactions in an asymptotically optimal way such that each neuron fires approximately once in [Formula: see text] operations, where N is the number of neurons in the system. We note that quantifications used in computational modeling are often statistical, since measurements in a real experiment to characterize physiological systems are typically statistical, such as firing rate, interspike interval distributions, and spike-triggered voltage distributions. We emphasize that it takes much less computational effort to resolve statistical properties of certain I&F neuronal networks than to fully resolve trajectories of each and every neuron within the system. For networks operating in realistic dynamical regimes, such as strongly fluctuating, high-conductance states, our methods are designed to achieve statistical accuracy when very large time-steps are used. Moreover, our methods can also achieve trajectory-wise accuracy when small time-steps are used.


Color image indexing using BTC.
This paper presents a new application of a well-studied image coding technique, namely block truncation coding (BTC). It is shown that BTC can not only be used for compressing color images, it can also be conveniently used for content-based image retrieval from image databases. From the BTC compressed stream (without performing decoding), we derive two image content description features, one termed the block color co-occurrence matrix (BCCM) and the other block pattern histogram (BPH). We use BCCM and BPH to compute the similarity measures of images for content-based image retrieval applications. Experimental results are presented which demonstrate that BCCM and BPH are comparable to similar state of the art techniques.


Light-induced dynamics in conjugated bis(terpyridine) ligands--a case study toward photoactive coordination polymers.
Terpyridine coordination compounds have recently revealed their potential toward optoelectronic applications, which are based on (i) their excellent charge-transfer properties or (ii) intriguing luminescence properties of the systems, depending on their design. This article features recent work in dissecting the photophysical properties of such materials by investigating the photoinduced processes in individual molecular fragments. The article starts considering the terpyridine ligands themselves before discussing the impact of metal coordination. After shedding light into the interplay of different electronic states in the terpyridine complexes, first results of a single-molecule fluorescence study are presented, which allow for correlation of the overall luminescence properties with the structure of the polymer.


Accurate Calibration in Multi-Material 3D Bioprinting for Tissue Engineering.
Most of the studies in three-dimensional (3D) bioprinting have been traditionally based on printing a single bioink. Addressing the complexity of organ and tissue engineering, however, will require combining multiple building and sacrificial biomaterials and several cells types in a single biofabrication session. This is a significant challenge, and, to tackle that, we must focus on the complex relationships between the printing parameters and the print resolution. In this paper, we study the influence of the main parameters driven multi-material 3D bioprinting and we present a method to calibrate these systems and control the print resolution accurately. Firstly, poloxamer hydrogels were extruded using a desktop 3D printer modified to incorporate four microextrusion-based bioprinting (MEBB) printheads. The printed hydrogels provided us the particular range of printing parameters (mainly printing pressure, deposition speed, and nozzle z-offset) to assure the correct calibration of the multi-material 3D bioprinter. Using the printheads, we demonstrated the excellent performance of the calibrated system extruding different fluorescent bioinks. Representative multi-material structures were printed in both poloxamer and cell-laden gelatin-alginate bioinks in a single session corroborating the capabilities of our system and the calibration method. Cell viability was not significantly affected by any of the changes proposed. We conclude that our proposal has enormous potential to help with advancing in the creation of complex 3D constructs and vascular networks for tissue engineering.


Effects of the first hydration sphere and the bulk solvent on the spectra of the f(2) isoelectronic actinide compounds: U(4+), NpO(2)(+), and PuO(2)(2+).
The electronic spectra of the 5f(2) isoelectronic actinide compounds U(4+), NpO(2)(+), and PuO(2)(2+) have been investigated theoretically both in gas phase and in solution. In the latter case the solvent was modelled by a saturated first hydration sphere, five water molecules for NpO(2)(+), and PuO(2)(2+) and eight for U(4+), and a continuum model describing the remaining solvent. The transition energies and oscillator strengths were obtained at the spin-orbit level using the relativistic wave function based multi-configuration methods CASPT2 (complete active space with second-order perturbation theory) and MRCI + DC (Davidson corrected multi-reference configuration interaction), followed by a spin-orbit CI based on a dressed effective spin-orbit Hamiltonian. This study is an attempt to contribute to an enhanced understanding of the electronic structure of tetravalent actinide ions and actinyl(v) and (vi) ions. The spin-orbit MRCI and spin-orbit CASPT2 transitions energies have been compared for the bare ions, leading us to the conclusion that the spin-orbit CASPT2 approach is reasonably accurate and can be used with confidence for the calculation of the hydrated species. The first hydration sphere and the bulk solvent lift degeneracies, but the effect on the transition energies is fairly small for the two actinyl ions, while it is larger, up to several thousands of wave numbers for U(4+). The calculations allowed us to make assignments of the experimentally observed absorption spectra for all species. The computed transition energies and intensities compared favourably with experiment.