Miracle-dz/UniFAR-FTUs huggingface dataset:
Explaining why childhood abuse is a risk factor for poorer clinical course in bipolar disorder: a path analysis of 923 people with bipolar I disorder

Abstract Background Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity. Methods We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators. Results Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data. Conclusions Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.
Oropharyngeal Dysphagia in Breastfeeding Neonates with Hypoxic-Ischemic Encephalopathy on Therapeutic Hypothermia.

Purpose: To identify symptoms of oropharyngeal dysphagia (OPD) in breastfeeding neonates with hypoxic-ischemic encephalopathy (HIE) on therapeutic hypothermia (TH). Early identification of feeding problems in neonates with HIE by speech-language therapists (SLTs) may prevent secondary complications of OPD such as aspiration pneumonia and death. Materials and Methods: Twenty-eight full-term neonates with HIE (mean chronological age = 4.5 days) and 30 healthy term controls were prospectively recruited for this case-control study. Participants with HIE (mild [n = 15], moderate [n = 11], severe [n = 2]), diagnosed by pediatricians, received whole-body TH. Feeding was clinically evaluated by an SLT using the Preterm Infant Breastfeeding Behavior Scale. Results: Twenty-five neonates (89.2%) had at least one symptom of OPD. Falling asleep during feeding, noticeable oral secretions, coughing, and flaring nostrils were symptoms of OPD most frequently identified. The HIE group displayed limited arousal during breastfeeding and had less obvious rooting, shallower latching onto the breast, and more single sucks in comparison to term newborns. The HIE group had significantly more closed eyes and minimal movement during breastfeeding, while controls showed the quiet-alert state ideal for breastfeeding. Conclusions: OPD was identified in the majority of infants with HIE. Underlying the appearance of an inactive neonate with HIE may be OPD that could be overlooked if not investigated. Interprofessional collaboration between SLTs, pediatricians and nurses to determine feeding-readiness is imperative. SLTs may assist in decision-making to improve safety of breastfeeding in this population. This study contributes to the small body of research on early breastfeeding of neonates with HIE.
Antimicrobial Resistance in Methicillin-Resistant Staphylococcus aureus to Newer Antimicrobial Agents

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics. ABSTRACT Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics. Understanding the mechanisms of antimicrobial resistance (AMR) in MRSA provides insight into the optimal use of antimicrobial agents in clinical practice and also underpins critical aspects of antimicrobial stewardship programs. In this review we delineate the mechanisms, prevalence, and clinical importance of resistance to antibiotics licensed in the past 20 years that target MRSA, as well as new drugs in the pipeline which are likely to be licensed soon. Current gaps in scientific knowledge about MRSA resistance mechanisms are discussed, and topics in the epidemiology of AMR in S. aureus that require further investigation are highlighted.
Binding affinity data of DNA aptamers for therapeutic anthracyclines from microscale thermophoresis and surface plasmon resonance spectroscopy.

Anthracyclines like daunorubicin (DRN) and doxorubicin (DOX) play an undisputed key role in cancer treatment, but their chronic administration can cause severe side effects. For precise anthracycline analytical systems, aptamers are preferable recognition elements. Here, we describe the detailed characterisation of a single-stranded DNA aptamer DRN-10 and its truncated versions for DOX and DRN detection. Binding affinities were determined from surface plasmon resonance (SPR) and microscale thermophoresis (MST) and combined with conformational data from circular dichroism (CD). Both aptamers displayed similar nanomolar binding affinities to DRN and DOX, even though their rate constants differed as shown by SPR recordings. SPR kinetic data unravelled a two-state reaction model including a 1 : 1 binding and a subsequent conformational change of the binding complex. This model was supported by CD spectra. In addition, the dissociation constants determined with MST were always lower than that from SPR, and especially for the truncated aptamer they differed by two orders of magnitude. This most probably reflects the methodological difference, namely labelling for MST vs. immobilisation for SPR. From CD recordings, we suggested a specific G-quadruplex as structural basis for anthracycline binding. We concluded that the aptamer DRN-10 is a promising recognition element for anthracycline detection systems and further selected aptamers can be also characterised with the combined methodological approach presented here.
Reply to Crawford et al.: Why Trap-Neuter-Return (TNR) Is an Ethical Solution for Stray Cat Management

Simple Summary Much controversy surrounds the management of Australia’s unowned urban cat population. The longstanding practice of trapping and killing urban stray cats and kittens that are not reclaimed or adopted has proven ineffective at reducing their numbers. In addition, it has been shown that shelter staff tasked with the repeated killing of healthy animals often face severe mental health consequences. A growing body of scientific evidence from Australia and elsewhere indicates that a non-lethal alternative, trap-neuter-return (TNR), can be effective at reducing urban stray cat numbers. TNR has also been associated with declines in feline intake and euthanasia at animal shelters. A large-scale trial of TNR in Australia is warranted and needed urgently. An extensive yet fundamentally flawed argument against such a trial is presented in a recently published article, “A Case of Letting the Cat out of the Bag—Why Trap-Neuter-Return Is Not an Ethical Solution for Stray Cat (Felis catus) Management,” by Crawford et al. In the text that follows, we provided a rebuttal to the Crawford et al. paper and argued that TNR is an ethical, scientifically sound solution for the management of Australia’s urban stray cats. Abstract The recently published article, ‘A Case of Letting the Cat out of the Bag—Why Trap-Neuter-Return Is Not an Ethical Solution for Stray Cat (Felis catus) Management,’ by Crawford et al. warrants rebuttal. The case presented in the paper, opposing the initiation of TNR trials in Australia, ignores peer-reviewed evidence which substantiates the effectiveness of TNR at reducing unowned urban cat numbers. In addition, the paper’s authors offer a number of unrealistic recommendations, which are little more than a rebranding of the failed status quo. Urban stray cats have long been considered a problem across Australia. Current practice calls for the trapping and killing of thousands of healthy urban stray cats and kittens each year with no apparent effect on the total population. In contrast, the literature offers numerous examples, including two recent studies in Australia, of reductions in urban stray cat numbers where TNR has been implemented. TNR has also been associated with reduced feline intake and euthanasia at shelters, which improves both animal welfare and the well-being of shelter staff. A large-scale trial of TNR in an urban Australian context is scientifically justified and long overdue.
Molecular characterization of respiratory syncytial viruses circulating in a paediatric cohort in Amman, Jordan

Respiratory syncytial viruses (RSVs) are an important cause of mortality worldwide and a major cause of respiratory tract infections in children, driving development of vaccine candidates. However, there are large gaps in our knowledge of the local evolutionary and transmission dynamics of RSVs, particularly in understudied regions such as the Middle East. To address this gap, we sequenced the complete genomes of 58 RSVA and 27 RSVB samples collected in a paediatric cohort in Amman, Jordan, between 2010 and 2013. RSVA and RSVB co-circulated during each winter epidemic of RSV in Amman, and each epidemic comprised multiple independent viral introductions of RSVA and RSVB. However, RSVA and RSVB alternated in dominance across years, potential evidence of immunological interactions. Children infected with RSVA tended to be older than RSVB-infected children [30 months versus 22.4 months, respectively (P value = 0.02)], and tended to developed bronchopneumonia less frequently than those with RSVB, although the difference was not statistically significant (P value = 0.06). Differences in spatial patterns were investigated, and RSVA lineages were often identified in multiple regions in Amman, whereas RSVB introductions did not spread beyond a single region of the city, although these findings were based on small sample sizes. Multiple RSVA genotypes were identified in Amman, including GA2 viruses as well as three viruses from the ON1 sub-genotype that emerged in 2009 and are now the dominant genotype circulating worldwide. As vaccine development advances, further sequencing of RSV is needed to understand viral ecology and transmission, particularly in under-studied locations.
Effect of broiler breast abnormality and freezing on meat quality and metabolites assessed by 1 H-NMR spectroscopy

The present study aimed at investigating the impact of the current growth-related abnormalities (White-Striping—WS, Wooden Breast—WB, and Spaghetti Meat—SM) affecting broilers Pectoralis major muscles on the main quality traits, the oxidative stability of both the lipid and protein fraction as well as the water mobility assessed in fresh and frozen/thawed meat. In addition, Nuclear Magnetic Resonance spectroscopy (1 H-NMR) was applied to quantify free amino acids, histidine-containing dipeptides and metabolites involved in energy-generating pathways. Overall, the occurrence of WS, WB, and SM abnormalities remarkably affected the quality traits (pH, color, and water holding capacity) and oxidative stability of the meat, with the WB condition leading to the most detrimental effects. However, overall, freezing and subsequent thawing only partially worsened the aforementioned traits. Significant variations in free amino acids and histidine-containing dipeptides were found between abnormal muscles and their unaffected counterpart by 1 H-NMR spectroscopy and, aside from the occurrence of muscular defects, their content was remarkably reduced in frozen/thawed meat. The findings obtained by analyzing the metabolites through 1 H-NMR spectroscopy allowed to advance the knowledge concerning the impact of freezing and subsequent thawing on meat quality traits and provided useful information concerning the underlying mechanisms responsible for the development of WS, WB, and SM abnormalities in broilers.
Changes in prescription of antidepressants and disability pension due to back pain, compared with other musculoskeletal and other somatic diagnoses: a cohort study in Sweden

Objectives The aim was to investigate differences in the prescription of antidepressants during the transition to disability pension (DP) comparing DP due to back pain with DP due to other musculoskeletal and DP due to other somatic diagnoses. Design A population-based cohort study with follow-up 3 years before and after the event. Estimated prevalence and adjusted ORs with 95% CIs for antidepressant prescription were computed for the 7-year window (ie, t-3 to t+3) around the DP by generalised estimating equations for repeated measures. Setting and participants This Swedish population-based nationwide study with registry data included individuals aged 18–64 years, with DP due to back pain (n=2011), DP due to other musculoskeletal (n=3548) or DP due to other somatic diagnoses (n=11 809). Primary outcome measures Prescription of antidepressants. Results Before DP, the prevalence of prescription of antidepressants was stable in DP due to back pain, but increased for the other DP groups. Similarly, the likelihood of prescription increased only marginally before DP due to back pain (ORs from 0.86 at t-3 to 1.10 at t-1), but clearly in DP due to musculoskeletal (from 0.42 to 1.15) and somatic diagnoses (from 0.29 to 0.98). Both prevalence measures and risks remained at the elevated levels after DP. Conclusions Pathways to DP due to musculoskeletal and somatic diagnoses seem to be partly driven by adverse mental health, which remains at a higher level after DP. The increasing prescription of antidepressants prior to DP suggests that special attention should be paid to mental health for prevention of DP. The period after DP needs attention to avoid deterioration of mental health.
Rotavirus Epidemiology and Monovalent Rotavirus Vaccine Effectiveness in Australia: 2010–2017

After a rotavirus outbreak, we describe overall rotavirus disease epidemiology and evaluate VE in Australia’s largest state using notification, genotypic, and immunization register data. BACKGROUND: Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia, from that time. In 2017, New South Wales experienced a large outbreak of rotavirus gastroenteritis. We examined epidemiology, genotypic profiles, and vaccine effectiveness (VE) among cases. METHODS: Laboratory-confirmed cases of rotavirus notified in New South Wales between January 1, 2010 and December 31, 2017 were analyzed. VE was estimated in children via a case-control analysis. Specimens from a sample of hospitalized case patients were genotyped and analyzed. RESULTS: In 2017, 2319 rotavirus cases were reported, representing a 3.1-fold increase on the 2016 notification rate. The highest rate was among children aged <2 years. For notified cases in 2017, 2-dose VE estimates were 88.4%, 83.7%, and 78.7% in those aged 6 to 11 months, 1 to 3 years, and 4 to 9 years, respectively. VE was significantly reduced from 89.5% within 1 year of vaccination to 77.0% at 5 to 10 years postvaccination. Equinelike G3P[8] (48%) and G8P[8] (23%) were identified as the most common genotypes in case patients aged ≥6 months. CONCLUSIONS: Rotarix is highly effective at preventing laboratory-confirmed rotavirus in Australia, especially in infants aged 6 to 11 months. Reduced VE in older age groups and over time suggests waning protection, possibly related to the absence of subclinical immune boosting from continuously circulating virus. G8 genotypes have not been common in Australia, and their emergence, along with equinelike G3P[8], may be related to vaccine-induced selective pressure; however, further strain-specific VE studies are needed.
Seasonal influenza vaccination among primary health care workers in Southwestern Saudi Arabia

ABSTRACT Background: Vaccination of primary healthcare workers (PHCWs) help to prevent the spread of influenza among at-risk patients. Objectives: To assesses seasonal influenza vaccination (SIV) coverage and the factors affecting SIV’s utilization among PHCWs in Abha city, southwestern Saudi Arabia. Methods: A cross-sectional survey was carried out between June 2018 and August 2018 in all primary healthcare centers in Abha city. It targeted physicians, nurses, technicians, and pharmacists. A self-administered questionnaire was used to collect data regarding SIV status during the 2017–2018 season, obtain knowledge regarding SIV and influenza disease, and identify potential motivators for and barriers to SIV. Results: Of 312 PHCWs, the SIV coverage rate was 45.5% in the 2017–2018 vaccination season. A multivariable logistic regression model showed that the risk groups for non-vaccination were PHCWs less than 40 years old (adjusted Odds Ratio (aOR) = 4.07, 95% CI: 1.50–11.03), technicians (aOR = 3.73, 95% CI: 1.20–11.54), single PHCWs (aOR = 2.36, 95% CI:1.20–4.62), and PHCWs lacking adequate influenza vaccine knowledge (aOR = 4.22, 95% CI: 2.13–8.35). Approximately 23% and 32% of PHCWs were found to have inadequate knowledge about SIV and influenza disease, respectively. PHCWs’ awareness about their risk of infection and their need for protection was found to be the most common motivator (77.5%), and a fear of side effects was found to be the most frequent barrier (40%). Conclusion: SIV coverage rate is suboptimal. Knowledge gaps and misconceptions about the influenza vaccine are the main barriers to an adequate coverage.
Off-Label Prescribing in Children Remains High: A Call for Prioritized Research

* Abbreviations: BPCA — : Best Pharmaceuticals for Children Act PREA — : Pediatric Research Equity Act The US Food and Drug Administration requires that medications be tested for safety and efficacy at a specific dosage, and for a specific time period, before approval for clinical use in a particular population.1 Use of medications outside these parameters is considered “off-label” drug use. Historically, studies evaluating medications in the pediatric population have been challenging. Children present unique considerations in clinical trials owing to scientific, ethical, clinical, and logistic concerns, which have previously limited and even discouraged the testing of medications in this population.1 Consequently, the majority of medications used in the care of children have historically been used off label without an adequate … Address correspondence to Katelyn Yackey, MD, Department of Emergency Medicine, University of Kentucky, 800 Rose St, Room M53, Lexington, KY 40536. E-mail: katelyn.yackey{at}uky.edu
Cognitive control of emotional distraction – valence-specific or general?

ABSTRACT Emotional information captures attention due to privileged processing. Consequently, performance in cognitive tasks declines (i.e. emotional distraction, ED). Therefore, shielding current goals from ED is essential for adaptive goal-directed- behaviour. It has been shown that ED is reduced when participants recruit cognitive control before or after the presentation of an emotional negative distractor. Following up on this, we asked first, whether cognitive control of ED is negative-valence-specific or valence-general. A valence-general-account predicts that control shields against distracting influence of emotion, irrespective of the specific valence. In contrast, a negative-valence-specific-account predicts that control interacts with the valence and ED is reduced for negative stimuli only. Second, we asked whether this effect of ED differs between control modes operating on different time scales (i.e. proactively or reactively). To test this, we manipulated emotional distractor valence (positive/high-arousal; negative/high-arousal; neutral/low-arousal) and assessed how control interacts with ED. Results showed that ED was reduced for negative and positive valent stimuli when control was triggered before (i.e. proactive control, nExp1 = 141, between-subject-design) and after (reactive control, nExp2 = 37, within-subject-design) the emotional stimuli. Accordingly, control blocks off high-arousing emotional distractors from interfering with goal-directed-actions, irrespective of their valence (i.e. valence-general-account) and for both, proactive and reactive control modes.
Prevalence of polycystic kidney disease in Persian and Persian related-cats referred to Small Animal Hospital, University of Tehran, Iran.

Background Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited genetic disease of cats, predominantly affecting Persians and Persian-related cats. Aims The purpose of this study was to determine prevalence of polycystic kidney disease (PKD) in Persian cats in Iran, and also to assess the relationships between PKD and gender, age as well as clinical and paracilinical manifestations. Methods Sonographic screening examination was performed on all healthy and unhealthy Persian and Persian-related cats referred to Small Animal Hospital of Faculty of Veterinary Medicine, University of Tehran, from April 2014 to May 2015. Cats were classified as positive when at least one anechoic cavity was found in at least one kidney. Results Of 76 Persian and Persian-related cats submitted for PKD ultrasound screening, 36.8% were found to have the disease and 63.2% were negative. Therefore, the prevalence of PKD was estimated 36.8% in Persian and Persian related cats in Tehran, Iran, which is approximately similar to prevalence in other parts of the world. Furthermore, there was a significant correlation between PKD and age, as in affected cats the detection probability of renal cysts in sonography was increased in older animals. For each year increase in age, the detection probability of PKD in sonography was increased about 2.62 times. Conclusion The prevalence of the PKD amongst Persian cats in Iran is relatively high, and insufficient attention to incidence and prevalence of PKD especially in breeding programs, would spread the disease throughout in Persian cats.
Behavioral and immunohistochemical characterization of rapid reconditioning following extinction of contextual fear

A fundamental property of extinction is that the behavior that is suppressed during extinction can be unmasked through a number of postextinction procedures. Of the commonly studied unmasking procedures (spontaneous recovery, reinstatement, contextual renewal, and rapid reacquisition), rapid reacquisition is the only approach that allows a direct comparison between the impact of a conditioning trial before or after extinction. Thus, it provides an opportunity to evaluate the ways in which extinction changes a subsequent learning experience. In five experiments, we investigate the behavioral and neurobiological mechanisms of postextinction reconditioning. We show that rapid reconditioning of unsignaled contextual fear after extinction in male Long–Evans rats is associative and not affected by the number or duration of extinction sessions that we examined. We then evaluate c-Fos expression and histone acetylation (H4K8) in the hippocampus, amygdala, prefrontal cortex, and bed nucleus of the stria terminalis. We find that in general, initial conditioning has a stronger impact on c-Fos expression and acetylation than does reconditioning after extinction. We discuss implications of these results for theories of extinction and the neurobiology of conditioning and extinction.