Gender differences in PTSD severity and pain outcomes: baseline results from the LAMP trial.

Background: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD. Aim: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. Methods: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. Results: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). Conclusion: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

The protected antimicrobial process in a University Teaching Hospital: a qualitative interview study exploring the knowledge, attitudes, and experiences of healthcare professionals.

Background The protected or restricted supply of certain antimicrobials such as linezolid, caspofungin, aztreonam, in the acute hospital setting is an important element of Antimicrobial Stewardship (AMS) programmes to address the growing problem of antimicrobial resistance. This process involves submitting an application for use to be reviewed typically by a Consultant Microbiologist, Infectious Disease Consultant or Antimicrobial Pharmacist. Aim To investigate healthcare professionals' knowledge, experiences, and attitudes towards the protected/restricted antimicrobials process in order to identify possible methods of optimisation and improvement. Method Semi-structured interviews with stakeholders involved in the protected/restricted antimicrobial prescribing, dispensing and administration process were conducted in September-October 2019 in a 350-bed voluntary, general, acute hospital in Ireland. Interviews were analysed by the Framework method and mapped to the Theoretical Domains Framework (TDF). Results Interviews were conducted with 8 Doctors, 4 Pharmacists and 3 Nurses. TDF domains identified included: 'Knowledge'; 'Social/professional role and identity'; 'Social influences'; 'Memory, attention and decision processes'; 'Beliefs about consequences'; 'Environmental contexts and resources'. The relationship between prescribers and the AMS Team was reported as a facilitator of the process, whereas the inconsistency of the filing and versions of forms on the wards were seen as challenges. Conclusion The results of this study have shown that the existing protected/restricted antimicrobial process is a multi-disciplinary effort with barriers that require attention in order to make future improvements. Standardization of the form across all wards, an electronic version of the form, and structured education around AMS were suggested to optimize the process.

Impact on patients of the coronovirus disease 2019 pandemic and postponement of cochlear implant surgery: a qualitative study.

OBJECTIVE: This study aimed to explore the impact of the coronavirus disease 2019 pandemic and postponement of elective surgical procedures for profoundly deaf patients awaiting cochlear implantation. METHOD: Open-ended questionnaires were sent to all adult patients awaiting cochlear implantation surgery. Qualitative analysis was performed using a grounded theory approach. RESULTS: Participants described a primarily negative impact on wellbeing from the surgery delay, expressing feelings of isolation or loneliness. Low mood, depression or hopelessness were commonly expressed by elderly participants; frustration and anxiety were described by young adults. Participants described a negative impact on their general daily life, describing difficulties communicating with facemasks and struggles with reliance on telephone communication because of social distancing. Despite these significant psychosocial challenges, only a minority described adaptive coping strategies. DISCUSSION: Profoundly deaf patients may be at greater psychosocial risk because of unique challenges from their hearing disability. Our findings can be used to develop evidence-driven strategies to improve communication, wellbeing and quality of life.

Exploring factors having an impact on attitudes and motivations towards volunteering in the undergraduate nursing student population - A comparative study of the UK and Ghana.

This study explores attitudes and motivations towards volunteering in nursing students in Ghana compared with nursing students in the United Kingdom (UK). Ghana traditionally follows a western model of nurse education, with students studying programmes commensurate in theory and practice, making Ghana a suitable location for a comparative study. We explored similarities and differences in attitudes and motivation towards volunteering to challenge and inform our common place practice towards nursing pedagogy. Ghanaian students displayed positive attitudes towards volunteering, although these did not translate into increased motivation to volunteer while at university. Students reported financial constraints as reasons for not volunteering as did UK students, although Ghanaian students used available resources for daily living expenses, whereas UK students prioritised available resources to pay down student debt. Structured volunteering was absent from both Ghanaian and UK nursing programmes, despite its potential to increase the variety of social groups or situations to which students are exposed, to increase self-confidence and to encourage greater reflection on practice through doing. Structural challenges within countries may provide a better explanation of variation in student motivation towards volunteering, than cross-cultural variation in attitudes towards volunteering between countries.

High-Resolution Differentiation of Enteric Bacteria in Premature Infant Fecal Microbiomes Using a Novel rRNA Amplicon.

Identifying and tracking microbial strains as microbiomes evolve are major challenges in the field of microbiome research. We utilized a new sequencing kit that combines DNA extraction with PCR amplification of a large region of the rRNA operon and downstream bioinformatic data analysis. Longitudinal microbiome samples of coadmitted twins from two different neonatal intensive care units (NICUs) were analyzed using an ∼2,500-base amplicon that spans the 16S and 23S rRNA genes and mapped to a new, custom 16S-23S rRNA database. Amplicon sequence variants (ASVs) inferred using DADA2 provided sufficient resolution for the differentiation of rRNA variants from closely related but not previously sequenced Klebsiella, Escherichia coli, and Enterobacter strains, among the first bacteria colonizing the gut of these infants after admission to the NICU. Distinct ASV groups (fingerprints) were monitored between coadmitted twins over time, demonstrating the potential to track the source and spread of both commensals and pathogens. The high-resolution taxonomy obtained from long amplicon sequencing enables the tracking of strains temporally and spatially as microbiomes are established in infants in the hospital environment.IMPORTANCE Achieving strain-level resolution is a major obstacle for source tracking and temporal studies of microbiomes. In this study, we describe a novel deep-sequencing approach that provides species- and strain-level resolution of the neonatal microbiome. Using Klebsiella, E. coli, and Enterobacter as examples, we could monitor their temporal dynamics after antibiotic treatment and in pairs of twins. The strain-level resolution, combined with the greater sequencing depth and decreased cost per read of PacBio Sequel 2, enables this advantageous source- and strain-tracking analysis method to be implemented widely across more complex microbiomes.

The nucleus acts as a ruler tailoring cell responses to spatial constraints.

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.

Differences in nasal immunoglobulin A responses to influenza vaccine strains after live attenuated influenza vaccine (LAIV) immunization in children.

Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open-label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi-factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation.

A case report of albendazole toxicity mimicking tetanus in an Anglo-Nubian ­ Alpine cross goat (Capra hircus)

An unvaccinated pregnant two-year-old Anglo- Nubian ­ Alpine crossed doe presented to The University of the West Indies School of Veterinary Medicine in lateral recumbency with bilaterally stiff hind limbs. The owner indicated that he had dewormed the animal three days prior with 380mg of Albendazole per os and that the doe started experiencing seizures two days later. On clinical physical examination, the animal was bloated and had severe ocular lesions to the right eye including corneal oedema and ulceration and a miotic and non-responsive pupil. Abdominal ultrasound suggested the presence of two foetuses but their viability could not be confirmed as only one heartbeat was detected. The doe was initially treated with tetanus antitoxin, parenteral antibiotics, non-steroidal anti-inflammatory medication, intravenous fluids and anticonvulsants. Two days later, she aborted two foetuses. Once the doe was stabilized, physiotherapy and hydrotherapy were performed. Within two weeks of initial presentation, she had regained a healthy appetite and was able to stand and walk unassisted. Despite the similarities between the initial clinical signs to that of tetanus, the abortion, subsequent case progression and eventual resolution of clinical signs are more consistent with the final diagnosis of albendazole toxicity. This case is important as it demonstrates how the indiscriminate use of anthelmintics and the lack of proper deworming strategies can potentially result in animal fatalities. Appropriate anthelmintic use is essential for both animal health and continued drug efficacy. Veterinarians should also be aware of the striking similarities in clinical signs of albendazole toxicity with those of tetanus.

An evaluation of the implementation of a parent-led, games-based physical activity intervention: the Active Play at Home quasi-randomized trial.

Trial Registration: NCT02058342. Registered 6 February 2014 retrospectively registered.

The impact of timing of maternal influenza immunization on infant antibody levels at birth.

Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunization is a potent tool to protect both these at-risk groups. While the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunized in the second trimester of pregnancy had the highest antibody titres compared to children immunized in the third trimester. The aim of the current study was to investigate how the timing of maternal influenza immunization impacts infant antibody levels at birth. Antibody titres were assessed in maternal and cord blood samples by both immunoglobulin (Ig)G-binding enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition assay (HAI). Antibody titres to the H1N1 component were significantly higher in infants born to mothers vaccinated in either the second or third trimesters than infants born to unvaccinated mothers. HAI levels in the infant were significantly lower when maternal immunization was performed less than 4 weeks before birth. These studies confirm that immunization during pregnancy increases the antibody titre in infants. Importantly, antibody levels in cord blood were significantly higher when the mother was vaccinated in either trimesters 2 or 3, although titres were significantly lower if the mother was immunized less than 4 weeks before birth. Based on these data, seasonal influenza vaccination should continue to be given in pregnancy as soon as it becomes available.

Improved speech and language development after unilateral cochlear implantation in children with a potentially useable contralateral ear.

OBJECTIVES: Increasingly, children are considered for a unilateral cochlear implant (CI), even if the contralateral ear falls outside current audiological guidelines, especially if they are not considered to be reaching their educational potential. Here we present the outcomes of CI in children with potentially useable hearing in the contralateral ear. METHODS: A retrospective case note review was performed for a total of 57 patients. Primary outcome was speech and language (SaL) development, as measured by the Manchester Speech and Language Development Scale (MSLDS) and SaL age equivalent. Secondary outcomes were auditory perception, perceived parental benefit and compliance; respectively measured by Categories of Auditory Performance (CAP), Brief Assessment of Parental Perception (BAPP) and reported use. RESULTS: SaL development improved after CI with a mean pre-operative MSLDS score of 5.8 to a postoperative score of 8.0 (n = 57) and a mean SaL age equivalent of 14 months in a one-year period (n = 14). Furthermore, CAP scores improved from 4.9 to 7.0 (n = 57). Analysis of BAPP scores showed improved quality of life in 18/19 patients (94.7%). With regards to compliance, 50/57 (87.7%) are fulltime users of both their CI and their HA. CONCLUSION: The present study indicates that despite one ear having potentially useable hearing outside national audiological criteria, the majority of participants received benefit from a CI in the poorer hearing ear. We suggest that assessment of each ear separately and treatment with the most appropriate amplification device, has given these children a benefit they may not otherwise have acquired if they only had bilateral HA.

Changes in cardiometabolic markers in children with Prader-Willi syndrome and nonsyndromic obesity following participation in a home-based physical activity intervention.

BACKGROUND: Physical activity is associated with improved cardiometabolic markers in children with nonsyndromic obesity (NSO). Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder characterized by obesity. OBJECTIVE: To compare cardiometabolic changes in response to a home-based parent-facilitated physical activity intervention between children with PWS or with NSO. METHODS: Participants included 18 children with PWS (age = 10.5 ± 0.7y; body fat = 44.6 ± 2.0%) and 30 children with NSO (age = 9.7 ± 0.2y; body fat = 44.8 ± 1.2%). Active Play @ Home was a 24-week physical activity intervention curriculum containing playground-based and active video games completed 4 days per week. Pre- and post-intervention measurements included physical activity, body composition, blood samples analysed for glucose, insulin, lipids and cytokines, and insulin resistance computed using the homeostatic model of assessment for insulin resistance (HOMA-IR). RESULTS: All children (n = 48) showed a significant decrease in Interleukin-8 (3.64 ± 0.24 vs. 3.06 ± 0.22 pg/mL). Children with obesity who did not gain or who lost body fat percentage (n = 18) demonstrated a significant decrease in HOMA-IR (3.17 ± 0.39 vs. 2.72 ± 0.34) and an increase in high-density lipoprotein (44.30 ± 2.51 vs. 47.29 ± 2.59 mg/dL). All other measurements showed no significant changes. CONCLUSIONS: The most favourable changes in cardiometabolic factors were observed in children with nonsyndromic obesity who demonstrated no gain or a decrease in body fat percentage.

Nutrient exports from watersheds with varying septic system densities in the North Carolina Piedmont.

Septic systems (SSs) have been shown to be a significant source of nitrogen and phosphorus to nutrient-sensitive coastal surface and groundwaters. However, few published studies have quantified the effects of SSs on nutrient inputs to water supply watersheds in the Piedmont region of the USA. This region consists of rolling hills at the surface underlain by clayey soils. There are nearly 1 million SSs in this region, which accounts for approximately 50% of all SSs in North Carolina. The goal of this study was to determine if significant differences in nutrient concentrations and exports exist between Piedmont watersheds with different densities of SSs. Water quality was assessed in watersheds with SSs (n = 11) and a sewer and a forested watershed, which were designated as controls. Stream flow and environmental readings were recorded and water samples were collected from the watersheds from January 2015-December 2016. Additional samples were collected from sand filter watersheds in April 2015-March 2016 to compare to septic and control watersheds. Samples were analyzed for total dissolved nitrogen (TDN) and orthophosphate (PO4-P). Results indicated that watersheds served by a high-density (HD) of SSs (4.9 kg-N yr-1 ha-1; 0.2 kg-P yr-1 ha-1) exported more than double the median masses of TDN and PO4-P, respectively, relative to low-density (1.0 kg-N yr-1 ha-1; <0.1 kg-P yr-1 ha-1) and control watersheds (1.4 kg-N yr-1 ha-1; <0.1 kg-P yr-1 ha-1) during baseflow. Isotopic analysis indicated that wastewater was the most likely source of nitrate-N in HD watersheds. In all other watersheds, isotopic results suggested non-wastewater sources as the dominant nitrate-N provider. These findings indicated that SS density was a significant factor in the delivery of septic-derived nutrients to these nutrient-sensitive, water supply watersheds of the North Carolina Piedmont.

Comprehensive molecular screening strategy of OCLN in band-like calcification with simplified gyration and polymicrogyria.

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). BLC-PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto-parietal, polymicrogyria. Here we report 4 additional cases of BLC-PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo-gene and copy number variants.

Use of dispersion modelling for Environmental Impact Assessment of biological air pollution from composting: Progress, problems and prospects.

With the increase in composting asa sustainable waste management option, biological air pollution (bioaerosols) from composting facilities have become a cause of increasing concern due to their potential health impacts. Estimating community exposure to bioaerosols is problematic due to limitations in current monitoring methods. Atmospheric dispersion modelling can be used to estimate exposure concentrations, however several issues arise from the lack of appropriate bioaerosol data to use as inputs into models, and the complexity of the emission sources at composting facilities. This paper analyses current progress in using dispersion models for bioaerosols, examines the remaining problems and provides recommendations for future prospects in this area. A key finding is the urgent need for guidance for model users to ensure consistent bioaerosol modelling practices.

Hearing optimisation in neurofibromatosis type 2: A systematic review.

BACKGROUND: It is common for patients with neurofibromatosis type 2 to develop bilateral profound hearing loss hearing loss, and this is one of the main determinants of quality of life in this patient group. OBJECTIVES: The aim of this systematic review was to review the current literature regarding hearing outcomes of treatments for vestibular schwannomas in neurofibromatosis type 2 including conservative and medical management, radiotherapy, hearing preservation surgery and auditory implantation in order to determine the most effective way of preserving or rehabilitating hearing. SEARCH STRATEGY: A MESH search in PubMed using search terms (('Neurofibromatosis 2' [Mesh]) AND 'Neuroma, Acoustic'[Mesh]) AND 'Hearing Loss' [Mesh] was performed. A search using keywords was also performed. Studies with adequate hearing outcome data were included. With the exception of the cochlear implant studies (cohort size was very small), case studies were excluded. EVALUATION METHOD: The GRADE system was used to assess quality of publication. Formal statistical analysis of data was not performed because of very heterogenous data reporting. RESULTS: Conservative management offers the best chance of hearing preservation in stable tumours. The use of bevacizumab probably improves the likelihood of hearing preservation in growing tumours in the short term and is probably more effective than hearing preservation surgery and radiotherapy in preserving hearing. Of the hearing preservation interventions, hearing preservation surgery probably offers better hearing preservation rates than radiotherapy for small tumours but recurrence rates for hearing preservation surgery were high. For patients with profound hearing loss, cochlear implantation provides significantly better auditory outcomes than auditory brainstem implantation. Patients with untreated stable tumours are likely to achieve the best outcomes from cochlear implantation. Those who have had their tumours treated with surgery or radiotherapy do not gain as much benefit from cochlear implantation than those with untreated tumours. CONCLUSIONS: This review summarises the current literature related to hearing preservation/rehabilitation in patients with NF2. Whilst it provides indicative data, the quality of the data was low and should be interpreted with care. It is also important to consider that the management of vestibular schwannomas in NF2 is complex and decision-making is determined by many factors, not just the need to preserve hearing.

Increase in migraine diagnoses and guideline-concordant treatment in veterans, 2004-2012.

Background and aim Health administrators, policy makers, and educators have attempted to increase guideline adherence of migraine medications while reducing inappropriate use of opioid- and barbiturate-containing medications. We evaluated the burden of migraine and proportion of guideline-concordant care in a large, national health care system over time. Methods We conducted a time-series study using data from the Veterans Health Administration (VHA) electronic health record. Veterans with migraines were identified by ICD-9 code (346.X). Prescriptions and comorbid conditions were evaluated before and after migraine diagnosis. Chi-square tests and logistic regression were performed. Results A total of 57,064 veterans were diagnosed with migraine headache (5.3%), with women significantly more likely diagnosed (11.6% vs. 4.4%, p < 0.0001). The number of veterans diagnosed with migraine has significantly increased over the years. By 2012, triptans were prescribed to 43% of people with migraine, with no difference by gender. However, triptan prescriptions increased from 2004 to 2012 in men, but not women, veterans. Preventive medicines showed a significant increase with the year of migraine diagnosis, after controlling for age, sex, race, and for comorbidities treated with medications used for migraine prevention. Conclusions The burden of migraines is increasing within the VHA, with a corresponding increase in the delivery of guideline-concordant acute and prophylactic migraine-specific medication.

Differential KrasV12 protein levels control a switch regulating lung cancer cell morphology and motility.

INTRODUCTION: Oncogenic Kras mutations are important drivers of lung cancer development and metastasis. They are known to activate numerous cellular signaling pathways implicated in enhanced proliferation, survival, tumorigenicity and motility during malignant progression. OBJECTIVES: Most previous studies of Kras in cancer have focused on the comparison of cell states in the absence or presence of oncogenic Kras mutations. Here we show that differential expression of the constitutively active mutation KrasV12 has profound effects on cell morphology and motility that drive metastatic processes. METHODS: The study relies on lung cancer cell transformation models, patient-derived lung cancer cell lines, and human lung tumor sections combined with molecular biology techniques, live-cell imaging and staining methods. RESULTS: Our analysis shows two cell functional states driven by KrasV12 protein levels: a non-motile state associated with high KrasV12 levels and tumorigenicity, and a motile state associated with low KrasV12 levels and cell dissemination. Conversion between the states is conferred by differential activation of a mechano-sensitive double-negative feedback between KrasV12/ERK/Myosin II and matrix-adhesion signaling. KrasV12 expression levels change upon cues such as hypoxia and integrin-mediated cell-matrix adhesion, rendering KrasV12 levels an integrator of micro-environmental signals that translate into cellular function. By live cell imaging of tumor models we observe shedding of mixed high and low KrasV12 expressers forming multi-functional collectives with potentially optimal metastatic properties composed of a highly mobile and a highly tumorigenic unit. DISCUSSION: Together these data highlight previously unappreciated roles for the quantitative effects of expression level variation of oncogenic signaling molecules in conferring fundamental alterations in cell function regulation required for cancer progression.

Novel mutation in the fumarate hydratase gene in a patient with Reed syndrome.

Reed syndrome is an autosomal dominant disorder characterized by cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma caused by mutations in the fumarate hydratase gene. Dermatologic evaluation is often the first or only opportunity to discover the diagnosis of Reed syndrome in affected patients, which may prove to be life-saving. We present a 40-year-old woman with history of large uterine leiomyomas who presented with a two-year history of a pruritic papular eruption on the left neck refractory to topical corticosteroids. After histopathologic examination and genetic work-up, the patient was found to have a novel mutation in the fumarate hydratase gene and was subsequently diagnosed with Reed syndrome.