Miracle-dz/UniFAR-FTUs huggingface dataset:
Standing the test of time: Reflecting on the relevance today of Levinson’s Pet-Oriented Child Psychotherapy

Having the opportunity to re-read Pet-Oriented Child Psychotherapy was like visiting an old friend and reminiscing about times gone by all too fast. The re-read allowed me an opportunity to conceptualize how many of Levinson’s early tenets continue to be relevant today. As a trailblazer, Levinson made a discovery that drastically changed the way we view and understand the power of the human animal bond.
High-Efficiency Bridgeless Three-Level Power Factor Correction Rectifier

A high-efficiency bridgeless three-level power factor correction (PFC) rectifier is proposed. The circuit configuration of the proposed rectifier consists of four metal oxide semiconductor field-effect transistor (MOSFET) switches, and the reverse recovery problems of the switches are eliminated. Also, the proposed rectifier with three voltage levels reduces the power losses, harmonic components, voltage ratings, and electromagnetic interference. To control the grid current and the output voltage effectively, a feed-forward nominal voltage compensator with the mode selector is developed; by presetting the operating point of the grid voltage, this compensator improves the control environment. Thus, the proposed three-level PFC rectifier with developed control algorithm provides high power quality and high efficiency of 99.05%. Experimental results based on a 1-kW prototype are provided to evaluate its performance and verify the analysis.
Interactions of Oximino-Substituted Boronic Acids and β-Lactams with the CMY-2-Derived Extended-Spectrum Cephalosporinases CMY-30 and CMY-42

ABSTRACT CMY-30 and CMY-42 are extended-spectrum (ES) derivatives of CMY-2. ES characteristics are due to substitutions of Gly (CMY-30) and Ser (CMY-42) for Val211 in the Ω-loop. To characterize the effects of 211 substitutions, we studied the interactions of CMY-2, -30, and -42 with boronic acid transition state inhibitors (BATSIs) resembling ceftazidime and cefotaxime, assessed thermal stability of the enzymes in their free forms and in complexes with BATSIs and oximino-β-lactams, and simulated, using molecular dynamics (MD), the CMY-42 apoenzyme and the CMY-42 complexes with ceftazidime and the ceftazidime-like BATSI. Inhibition constants showed that affinities between CMY-30 and CMY-42 and the R1 groups of BATSIs were lower than those of CMY-2. ES variants also exhibited decreased thermal stability either as apoenzymes or in covalent complexes with oximino compounds. MD simulations further supported destabilization of the ES variants. Val211Ser increased thermal factors of the Ω-loop backbone atoms, as previously observed for CMY-30. The similar effects of the two substitutions seemed to be due to a less-constrained Tyr221 likely inducing concerted movement of elements at the edges of the active site (Ω-loop–Q120 loop–R2 loop/H10 helix). This inner-protein movement, along with the wider R1 binding cleft, enabled intense vibrations of the covalently bound ceftazidime and ceftazidime-like BATSIs. Increased flexibility of the ES enzymes may assist the productive adaptation of the active site to the various geometries of the oximino substrates during the reaction (higher frequency of near-attack conformations).
Autism and attachment difficulties: Overlap of symptoms, implications and innovative solutions

This article explores overlap of symptoms between autism and attachment difficulties and suggests innovative solutions based on formulation. Currently, clinicians express difficulties in differentiating between these conditions contributing to misdiagnosis. Research into the prevalence of attachment difficulties among children with autism often fails to reflect detailed knowledge of attachment theory. Consequently, studies in this area employ questionable modifications to attachment measures and methods of analysis. The findings of such studies are confusing and inconsistent. Children with autism and their parents are, however, known to be at high risk of developing insecure attachment patterns. Clinical assessments based on formulation may be helpful in these cases, as they include consideration of developmental and relational factors contributing to symptom presentation. Research suggests that where parents of children with autism establish secure relationships with their children outcomes are improved. Consequently, interventions, which improve dyadic synchrony and sensitivity of parents, are likely to benefit families living with autism and attachment difficulties.
Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae

ABSTRACT Antibiotic-resistant strains of Klebsiella pneumoniae often exhibit porin loss. In this study, we investigated how porin loss impacted the composition of secreted outer membrane vesicles as well as their ability to trigger proinflammatory cytokine secretion by macrophages. We hypothesize that porin loss associated with antibiotic resistance will directly impact both the composition of outer membrane vesicles and their interactions with phagocytic cells. Using clonally related clinical isolates of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae with different patterns of porin expression, we demonstrated that altered expression of OmpK35 and OmpK36 results in broad alterations to the protein profile of secreted vesicles. Additionally, the level of OmpA incorporation was elevated in strains lacking a single porin. Porin loss significantly impacted macrophage inflammatory responses to purified vesicles. Outer membrane vesicles lacking both OmpK35 and OmpK36 elicited significantly lower levels of proinflammatory cytokine secretion than vesicles from strains expressing one or both porins. These data demonstrate that antibiotic resistance-associated porin loss has a broad and significant effect on both the composition of outer membrane vesicles and their interactions with phagocytic cells, which may impact bacterial survival and inflammatory reactions in the host.
Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

ABSTRACT HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.
Educational Status and Risk of HIV in Young Gay Men

Lower socioeconomic status (SES) has been associated with higher rates of HIV infection as well as higher rates of unsafe sex. The behavioral determinants that might mediate the effect of SES on risky sex have not been studied thus far. We investigated the involvement of social cognitions in the link between educational status and unprotected anal sex in 292 participants of the Amsterdam Young Gay Men Study. We found that poorly educated men had poorer knowledge about HIV and preventive behavior, perceived social norms to be less favorable towards condom usage with casual partners, and had lower perceived control over that behavior than the better educated men. Poorly educated men were also more likely to have engaged in unprotected anal sex with casual partners in the six-month period that followed the assessment of the social cognitions. However, the education-related behavioral difference could not be explained by social cognitions. We concluded that cognitive models of behavior might not explain all of the risk behavior in gay men with lower SES. These men's risk-taking behavior might result from specific psychological characteristics of men with lower SES that interfere with traditional cognition–behavior correlations as posited in prevailing models of behavior.
Gender and Job Satisfaction of Information Technology Professionals in Poland

The objective of the study presented in this paper is to examine the effects of gender difference on the job satisfaction of information technology professionals in Poland, a transition economy. The necessary data is collected by a survey of 391 information technology professionals working in various regions of Poland. Several aspects of job satisfaction are investigated: satisfaction with pay, promotion, colleagues, supervision and work itself. The results indicate that women who work as information technology professionals in Poland are less satisfied than male colleagues with their compensation and promotion opportunities. Based on the findings, several promising research avenues related to this research are discussed.
Greater Ciprofloxacin Tolerance as a Possible Selectable Phenotype Underlying the Pandemic Spread of the H30 Subclone of Escherichia coli Sequence Type 131

ABSTRACT Minimum bactericidal concentrations (MBCs) for ciprofloxacin were significantly higher among 41 members of the H30 subclone within Escherichia coli sequence type 131 than among 48 other fluoroquinolone-resistant E. coli isolates. This MBC difference, which was not explained by ciprofloxacin MICs, gyrA, parC, and parE mutations, the presence of aac(6′)-Ib-cr, or organic solvent tolerance (a surrogate for efflux pump activity), conceivably could have promoted the pandemic emergence of the H30 sequence type 131 subclone.
Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis

ABSTRACT New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB). Pretomanid (PMD) is a nitroimidazole in phase 3 trials that has significant bactericidal activity alone and in combination with bedaquiline (BDQ) and/or pyrazinamide (PZA). We previously showed that the novel combination of BDQ+PMD plus the oxazolidinone sutezolid (SZD) had sterilizing activity superior to that of the first-line regimen in a murine model of TB. The present experiments compared the activity of different oxazolidinones in combination with BDQ+PMD with or without PZA in the same model. The 3-drug regimen of BDQ+PMD plus linezolid (LZD) had sterilizing activity approaching that of BDQ+PMD+SZD and superior to that of the first-line regimen. The addition of PZA further enhanced activity. Reducing the duration of LZD to 1 month did not significantly affect the activity of the regimen. Halving the LZD dose or replacing LZD with RWJ-416457 modestly reduced activity over the first month but not after 2 months. AZD5847 and tedizolid also increased the bactericidal activity of BDQ+PMD, but they were less effective than the other oxazolidinones. These results provide optimism for safe, short-course oral regimens for drug-resistant TB that may also be superior to the current first-line regimen for drug-susceptible TB.
Pharmacokinetics of Cefotaxime and Desacetylcefotaxime in Infants during Extracorporeal Membrane Oxygenation

ABSTRACT Extracorporeal membrane oxygenation (ECMO) is used to temporarily sustain cardiac and respiratory function in critically ill infants but can cause pharmacokinetic changes necessitating dose modifications. Cefotaxime (CTX) is used to prevent and treat infections during ECMO, but the current dose regimen is based on pharmacokinetic data obtained for non-ECMO patients. The objective of this study was to validate the standard dose regimen of 50 mg/kg of body weight twice a day (postnatal age [PNA], <1 week), 50 mg/kg three times a day (PNA, 1 to 4 weeks), or 37.5 mg/kg four times a day (PNA, >4 weeks). We included 37 neonates on ECMO, with a median (range) PNA of 3.3 (0.67 to 199) days and a median (range) body weight of 3.5 (2.0 to 6.2) kg at the onset of ECMO. Median (range) ECMO duration was 108 (16 to 374) h. Plasma samples were taken during routine care, and pharmacokinetic analysis of CTX and its active metabolite, desacetylcefotaxime (DACT), was done using nonlinear mixed-effects modeling (NONMEM). A one-compartment pharmacokinetic model for CTX and DACT adequately described the data. During ECMO, CTX clearance (CLCTX) was 0.36 liter/h (range, 0.19 to 0.75 liter/h), the volume of distribution of CTX (VCTX) was 1.82 liters (0.73 to 3.02 liters), CLDACT was 1.46 liters/h (0.48 to 5.93 liters/h), and VDACT was 11.0 liters (2.32 to 28.0 liters). Elimination half-lives for CTX and DACT were 3.5 h (1.6 to 6.8 h) and 5.4 h (0.8 to 14 h). Peak CTX concentration was 98.0 mg/liter (33.2 to 286 mg/liter). DACT concentration varied between 0 and 38.2 mg/liter, with a median of 10 mg/liter in the first 12 h postdose. Overall, CTX concentrations were above the MIC of 8 mg/liter over the entire dose interval. Only 1 of the 37 patients had a sub-MIC concentration for over 50% of the dose interval. In conclusion, the standard cefotaxime dose regimen provides sufficiently long periods of supra-MIC concentrations to provide adequate treatment of infants on ECMO.
Novel Broad-Spectrum Bis-(Imidazolinylindole) Derivatives with Potent Antibacterial Activities against Antibiotic-Resistant Strains

ABSTRACT Given the limited number of structural classes of clinically available antimicrobial drugs, the discovery of antibacterials with novel chemical scaffolds is an important strategy in the development of effective therapeutics for both naturally occurring and engineered resistant strains of pathogenic bacteria. In this study, several diarylamidine derivatives were evaluated for their ability to protect macrophages from cell death following infection with Bacillus anthracis, a gram-positive spore-forming bacterium. Four bis-(imidazolinylindole) compounds were identified with potent antibacterial activity as measured by the protection of macrophages and by the inhibition of bacterial growth in vitro. These compounds were effective against a broad range of gram-positive and gram-negative bacterial species, including several antibiotic-resistant strains. Minor structural variations among the four compounds correlated with differences in their effects on bacterial macromolecular synthesis and mechanisms of resistance. In vivo studies revealed protection by two of the compounds of mice lethally infected with B. anthracis, Staphylococcus aureus, or Yersinia pestis. Taken together, these results indicate that the bis-(imidazolinylindole) compounds represent a new chemotype for the development of therapeutics for both gram-positive and gram-negative bacterial species as well as against antibiotic-resistant infections.
Antimicrobial Susceptibilities of Health Care-Associated and Community-Associated Strains of Methicillin-Resistant Staphylococcus aureus from Hospitalized Patients in Canada, 1995 to 2008

ABSTRACT We determined the in vitro antimicrobial susceptibilities of 7,942 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients hospitalized in 48 Canadian hospitals from 1995 to 2008. Regional variations in susceptibilities were identified. The dissemination of community-associated strains in Canada appears to have contributed to increased susceptibility of MRSA to several non-β-lactam antimicrobial agents in the past decade. Reduced susceptibility to glycopeptides was not identified.
Women's Experience at the Time of Menopause: Accounting for Biological, Cultural and Psychological Embodiment

In understanding health and illness, it has long been apparent that psychological and social aspects are as important as the biological explanations of the biomedical model. Recent studies of women's experience of menopause have demonstrated the psychological and social constructions of women's bodies, but have neglected to include individual embodiment and the notion of a social world that is inescapably embodied. This paper presents arguments for the consideration of an integrated approach to embodiment and, drawing upon recent theorizing, a conceptual framework that is able to take into account the integration of psyche, biology, and culture. The accounts of 80 New Zealand women, aged between 45 and 60, are analysed, using categories labelled, ‘visceral’, ‘experiential’, ‘normative’ and ‘pragmatic’, to provide a description of women's embodied and culturally embedded experience of menopause. The incorporation of these analytic categories, and the usefulness of the application of the model in contemporary applied work, is discussed.
The Social and Ethical Implications of Changing Medical Technologies: The Views of People Living with Genetic Conditions

This article presents empirical data on subjective levels of health and quality of life for individuals with early- or late-onset genetic conditions. Twelve adults with an early-onset condition (cystic fibrosis) and 12 adults with a late-onset condition in the family (Huntington’s disease) participated in semi-structured interviews. Questions investigated perceptions of the body, quality of life and views on medical technology and testing. Transcripts were thematically analysed using a qualitative methodology (interpretative phenomenological analysis). The article focuses on the superordinate theme of ‘What is a life worth living? ’. Different emphases in judgements and definitions of quality of life were uncovered. At the same time the article emphasizes the convergence between the two groups in terms of overall views of quality of life and confirms that the voices of people living with genetic conditions should form part of wider bioethical debates arising from such advances.
The 6-Aminoquinolone WC5 Inhibits Human Cytomegalovirus Replication at an Early Stage by Interfering with the Transactivating Activity of Viral Immediate-Early 2 Protein

ABSTRACT WC5 is a 6-aminoquinolone that potently inhibits the replication of human cytomegalovirus (HCMV) but has no activity, or significantly less activity, against other herpesviruses. Here we investigated the nature of its specific anti-HCMV activity. Structure-activity relationship studies on a small series of analogues showed that WC5 possesses the most suitable pattern of substitutions around the quinolone scaffold to give potent and selective anti-HCMV activity. Studies performed to identify the possible target of WC5 indicated that it prevents viral DNA synthesis but does not significantly affect DNA polymerase activity. In yield reduction experiments with different multiplicities of infection, the anti-HCMV activity of WC5 appeared to be highly dependent on the viral inoculum, suggesting that WC5 may act at an initial stage of virus replication. Consistently, time-of-addition and time-of-removal studies demonstrated that WC5 affects a phase of the HCMV replicative cycle that precedes viral DNA synthesis. Experiments to monitor the effects of the compound on virus attachment and entry showed that it does not inhibit either process. Evaluation of viral mRNA and protein expression revealed that WC5 targets an event of the HCMV replicative cycle that follows the transcription and translation of immediate-early genes and precedes those of early and late genes. In cell-based assays to test the effects of WC5 on the transactivating activity of the HCMV immediate-early 2 (IE2) protein, WC5 markedly interfered with IE2-mediated transactivation of viral early promoters. Finally, WC5 combined with ganciclovir in checkerboard experiments exhibited highly synergistic activity. These findings suggest that WC5 deserves further investigation as a candidate anti-HCMV drug with a novel mechanism of action.
Coping Style Influences Compliance with Multidisciplinary Pain Management

The treatment of chronic pain disorders has become multifaceted in recognition of the complexities of chronic pain. However, few models have emerged to predict patients’ response to treatment. This study examined a path model of pain treatment outcome, incorporating the variables of coping style and treatment compliance. Results indicated that the suppression of negative emotion was associated with greater treatment compliance, whereas amplification of negative emotion was found to be associated with poorer treatment compliance. An aggressive coping style was found to be associated with poor treatment compliance. In turn, poor compliance predicted poor pre-/post-treatment functional capacity. Moreover, a path model incorporating compliance as a mediator between coping styles and functional impairment revealed an excellent model fit when compared to a path model with no mediators.
Pharmacokinetics of Darunavir/Ritonavir and Rifabutin Coadministered in HIV-Negative Healthy Volunteers

ABSTRACT The drug-drug interaction between rifabutin (RFB) and darunavir/ritonavir (DRV/r) was examined in a randomized, three-way crossover study of HIV-negative healthy volunteers who received DRV/r 600/100 mg twice a day (BID) (treatment A), RFB 300 mg once a day (QD) (treatment B), and DRV/r 600/100 mg BID plus RFB 150 mg every other day (QOD) (treatment C). The sequence of treatments was randomized, and each treatment period lasted 12 days. Full pharmacokinetic profiles were determined for DRV, ritonavir, and RFB and its active metabolite, 25-O-desacetylrifabutin (desRFB), on day 13. The DRV and ritonavir areas under the plasma concentration-time curve from zero to 12 h (AUC12h) increased by 57% and 66%, respectively, in the presence of RFB. The RFB exposure was comparable between treatment with RFB QD alone (treatment B) and treatment with DRV/r plus RFB QOD (treatment C); however, based on least-square means ratios, the minimum plasma concentration (Cmin) increased by 64% and the maximum plasma concentration (Cmax) decreased by 28%, respectively. The exposure (AUC within the dosage interval and at steady state [AUCτ]) to desRFB was considerably increased (by 881%) following treatment with DRV/r/RFB. The exposure to the parent drug plus the metabolite increased 1.6-fold in the presence of DRV/r. Adverse events (AEs) were more commonly reported during combined treatment (83% versus 44% for RFB and 28% for DRV/r); similarly, grade 3-4 AEs occurred in 17% versus 11% and 0%, respectively, of volunteers. Eighteen of 27 volunteers (66.7%) prematurely discontinued the trial; all volunteers discontinuing for safety reasons (n = 9) did so during RFB treatment phases. These results suggest that DRV/r may be coadministered with RFB with a dose adjustment of RFB to 150 mg QOD and increased monitoring for RFB-related AEs. Based on the overall safety profile of DRV/r, no dose adjustment of DRV/r is considered to be warranted. Given the safety profile seen with the combination of RFB with a boosted protease inhibitor in this and other studies, it is not recommended to conduct further studies with this combination in healthy volunteers.