Electrospun methacrylated natural/synthetic composite membranes for gingival tissue engineering.

New functional materials for engineering gingival tissue are still in the early stages of development. Materials for such applications must maintain volume and have advantageous mechanical and biological characteristics for tissue regeneration, to be an alternative to autografts, which are the current benchmark of care. In this work, methacrylated gelatin (GelMa) was photocrosslinked with synthetic immunomodulatory methacrylated divinyl urethanes and defined monomers to generate composite scaffolds. Using a factorial design, with the synthetic monomers of a degradable polar/hydrophobic/ionic polyurethane (D-PHI) and GelMa, composite materials were electrospun with polycarbonate urethane (PCNU) and light-cured in-flight. The materials had significantly different relative hydrophilicities, with unique biodegradation profiles associated with specific formulations, thereby providing good guidance to achieving desired mechanical characteristics and scaffold resorption for gingival tissue regeneration. In accelerated esterase/collagenase degradation models, the new materials exhibited an initial rapid weight loss followed by a more gradual rate of degradation. The degradation profile allowed for the early infiltration of human adipose-derived stromal/stem cells, while still enabling the graft's structural integrity to be maintained. In conclusion, the materials provide a promising candidate platform for the regeneration of oral soft tissues, addressing the requirement of viable tissue infiltration while maintaining volume and mechanical integrity. STATEMENT OF SIGNIFICANCE: There is a need for the development of more functional and efficacious materials for the treatment of gingival recession. To address significant limitations in current material formulations, we sought to investigate the development of methacrylated gelatin (GelMa) and oligo-urethane/methacrylate monomer composite materials. A factorial design was used to electrospin four new formulations containing four to five monomers. Synthetic immunomodulatory monomers were crosslinked with GelMa and electrospun with a polycarbonate urethane resulting in unique mechanical properties, and resorption rates which align with the original design criteria for gingival tissue engineering. The materials may have applications in tissue engineering and can be readily manufactured. The findings of this work may help better direct the efforts of tissue engineering and material manufacturing.

Plasma exchange-A useful adjunct therapy to red cell exchange in patients with sickle cell disease and multiorgan dysfunction.

BACKGROUND: Urgent red cell exchange (RBCx) is indicated for many complications of sickle cell disease (SCD), including acute chest syndrome, stroke, and hepatic/splenic sequestration. Many who receive RBCx remain hospitalized and develop further complications, including multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Therapeutic plasma exchange (TPE) has been advocated as an effective treatment of MODS, but its role in SCD compared with RBCx alone is not well studied. METHODS: We identified all ICU encounters from 2013 to 2019 involving RBCx procedures for MODS or SCD crisis that progressed to MODS, a total of 12 encounters. Data regarding hospital length of stay (LOS), survival, number of TPE procedures following RBCx, and procedure characteristics were collected. Surrogate laboratory markers of end-organ damage and disease severity scores were recorded at the time of admission, post-RBCx, post-TPE, and at discharge. RESULTS: Eight encounters involved RBCx followed by TPE (TPE group) while four involved RBCx alone (RBCx group). The TPE group had a higher SOFA score at ICU admission (9.5 vs. 7.0), greater predicted mortality, and a statistical trend toward higher disease severity scores following RBCx relative to the RBCx group (p = 0.10). The TPE group showed a significantly greater decrease in SOFA score between RBCx and discharge (p = 0.04). No significant difference in mortality or hospital LOS was observed between the groups. CONCLUSION: The findings suggest TPE may be considered as an adjunct treatment for patients with acute complications of SCD that progress to MODS, especially in cases where there is no significant improvement following RBCx.

Development and performance of a multiplex PCR assay for the detection of bacteria in sterile body fluids.

Aim: To assess the performance characteristics of a lab-developed multiplex PCR assay for the detection of common bacterial pathogens associated with infections in pediatric patients from normally sterile sites, such as cerebrospinal fluid, synovial and pleural fluids. Materials & methods: A total of 272 specimens were tested by PCR and traditional culture methods to assess the presence of Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus pyogenes, methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Kingella kingae. Results: Compared with culture, the overall positive and negative percentage agreement of the PCR were 95.9% and 74.1%, respectively. Conclusion: This sterile body fluid PCR affords a rapid and sensitive alternative for bacterial detection, allowing for more timely pathogen-directed antimicrobial therapy.

Within-category similarity negatively affects associative memory performance in both younger and older adults.

Associative memory involves the ability to encode and remember the relationship between individual items. This ability can become diminished when there is a high degree of similarity between stimuli that are being learned. Associative memory errors often stem from the fact that lures include a high degree of item familiarity as well as mnemonic similarity with the original associative episode. The current set of experiments examined how this overlap, in the form of within-category similarity, affects veridical and false retrieval in both younger and older adults. Across three experiments, results suggest that mnemonic overlap between targets and lures is detrimental to the ability to discriminate between highly similar information. Specifically, shared category membership for targets and lures led to increased false associative memories across age groups. These results have implications for scenarios where there is a high degree of overlap between target and lure events and indicate that these types of associative memory distinctions are difficult irrespective of age.

Effect of pre-operative oral paracetamol on gastric residual volume and pH in young children in the context of a 1-hour clear fluid fast: a randomised controlled trial.

High gastric residual volume and low pH are associated with increased mortality following pulmonary aspiration in animal studies. The use of pre-operative oral paracetamol has not been investigated in younger children and infants in the context of a prescriptive 1-h clear fluid fast aimed at reducing the risk of pulmonary aspiration while improving patient experience. Children aged 1 month up to a weight of 25 kg and scheduled for elective surgery were randomly allocated to receive a prescribed 3.6 ml.kg-1 drink of water alone (water group) or 3 ml.kg-1 water and oral Infant Calpol® syrup (24 mg.ml-1 concentration, equivalent volume 0.6 ml.kg-1 , paracetamol group) 1 h before the induction of anaesthesia. Following induction, a nasogastric tube was used to aspirate gastric contents and the volume and pH were recorded. Ninety-seven children, median (IQR [range]) age 24 (12-45 [1-96]) months and weight 12.4 (9.7-16.0 [2.9-27.0]) kg, were analysed. Median time from drink to induction was 54 (45-60 [21-113]) min. There was no significant difference in gastric residual volume (p = 1) or pH (p = 0.99) between the water and the paracetamol groups. Sub-group analysis revealed no significant difference in gastric residual volume or pH for 29 children who weighed < 10 kg compared with > 10 kg. Using a prescriptive fluid regime of 3 ml.kg-1 of water, the addition of oral paracetamol syrup did not significantly alter gastric residual volume or pH in the context of a 1-h fast in infants and young children.

Early inflammation precedes cardiac fibrosis and heart failure in desmoglein 2 murine model of arrhythmogenic cardiomyopathy.

The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in Dsg2-null (Dsg2-/-) hearts at postnatal day 14 (2 weeks) that were absent in the fibrotic heart of adult mice (10 weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression.

Prospective evaluation of a change in dietary therapy in dogs with steroid-resistant protein-losing enteropathy.

OBJECTIVE: To describe the clinical effect of dietary alteration as a sole change to therapy in dogs with steroid-resistant protein-losing enteropathy. MATERIALS AND METHODS: Prospective study. Eligible enrolled dogs received dietary alteration as sole change to their therapeutic plan. Canine Chronic Enteropathy Clinical Activity Index and serum albumin were monitored for the 3-month study period. Long-term follow-up data were also available for some of the study participants. RESULTS: Fifteen dogs were eligible for enrollment over the study period. Twelve were enrolled, 10 remained in the study at 30 days, nine completed the 3-month study period. Following dietary alteration, eight of 10 dogs achieved complete remission, one dog achieved partial remission and one dog had no response. Seven of eight dogs achieving complete remission have remained in remission up to 4 years following study. In dogs with complete remission, median Canine Chronic Enteropathy Clinical Activity Index score was 11.5 and 4, and median serum albumin concentration was 15 g/L and 26 g/L at 0 and 14-28 days, respectively. CLINICAL SIGNIFICANCE: Dogs with protein-losing enteropathy with previous lack of response to a combination of dietary therapies, glucocorticoids and immunosuppressive medications can achieve remission following a dietary change. Improvement is likely to be seen within 14 to 30 days. A change in dietary approach may be an alternative to further immunosuppression or anti-inflammatory strategies in some dogs with difficult to treat protein-losing enteropathy.

A rise in facial nerve palsies during the coronavirus disease 2019 pandemic.

OBJECTIVE: An increase in spontaneous lower motor neuron facial nerve (VIIth cranial nerve) palsies was seen during the severe acute respiratory syndrome coronavirus 2 outbreak in our emergency clinic. This led us to perform a single-centre cohort review. METHODS: A retrospective review was conducted of VIIth cranial nerve palsies from January to June 2020 and the findings were compared to those cases reviewed in the previous year. The severe acute respiratory syndrome coronavirus 2 incidence of the cohort was compared with that of the Liverpool population. RESULTS: Our VIIth cranial nerve palsy incidence in the 2020 period was 3.5 per cent (30 out of 852), 2.7 higher than last year's rate of 1.3 per cent (14 out of 1081), which was a statistically significant difference (p < 0.01). Two of the 17 patients in our cohort tested positive for severe acute respiratory syndrome coronavirus 2 (11.8 per cent), contrasting with Liverpool's severe acute respiratory syndrome coronavirus 2 incidence (0.5 per cent). CONCLUSION: Severe acute respiratory syndrome coronavirus 2 may be responsible for an increased number of facial nerve palsies; it is important for clinicians to be aware that this may being an initial presentation of the disease.

Canal wall down mastoidectomy with obliteration versus canal wall up mastoidectomy in primary cholesteatoma surgery.

OBJECTIVE: This study sought to compare disease recidivism rates between canal wall up mastoidectomy and a canal wall down with obliteration technique. METHODS: Patients undergoing primary cholesteatoma surgery at our institution over a five-year period (2013-2017) using the aforementioned techniques were eligible for inclusion in the study. Rates of discharge and disease recidivism were analysed using chi-square statistics. RESULTS: A total of 104 ears (98 patients) were included. The mean follow-up period was 30 months (range, 12-52 months). A canal wall down with mastoid obliteration technique was performed in 55 cases and a canal wall up approach was performed in 49 cases. Disease recidivism rates were 7.3 per cent and 16.3 per cent in the canal wall down with mastoid obliteration and canal wall up groups respectively (p = 0.02), whilst discharge rates were similar (7.3 per cent and 10.2 per cent respectively). CONCLUSION: Our direct comparative data suggest that canal wall down mastoidectomy with obliteration is superior to a canal wall up technique in primary cholesteatoma surgery, providing a lower recidivism rate combined with a low post-operative ear discharge rate.

The Effect of Thermal Treatment on the Hydrogen-Storage Properties of PIM-1.

There has been recent interest in polymers of intrinsic microporosity (PIMs) for solid-state hydrogen-storage materials; however, the gas-sorption properties and conditions for hydrogen uptake are relatively unexplored. PIM-1 has been synthesised using the condensation reaction between 3,3,3,3-tetramethyl-1,1-spirobisindane-5,5,6,6-tetraol and 2,3,5,6-tetrafluorophthalonitrile as precursors. The synthesised PIM-1 was annealed at different temperatures for varying times and then characterised for hydrogen uptake at both ambient and cryogenic temperatures. The excess hydrogen PCT isotherms have been measured to high pressure (320 bar) for the first time and the effect of different annealing conditions on the hydrogen capacity is reported.

The use of BRAF V600E mutation-specific immunohistochemistry in pediatric Langerhans cell histiocytosis.

BRAF p.V600E mutations are detected in greater than 50% of pediatric Langerhans cell histiocytosis (LCH) lesions. However, the use of mutation-specific BRAF V600E immunohistochemistry (IHC) as a surrogate for molecular testing in pediatric LCH is unknown. We tested the mutation-specific BRAF V600E monoclonal antibody (clone VE1) in formalin-fixed, paraffin-embedded LCH samples from 26 pediatric patients (14 males and 12 females, ages 7 mo-17 y) using allele-specific real-time polymerase chain reaction (PCR) with a limit of detection of 0.5% as the comparative gold standard. BRAF VE1 staining was scored for both intensity (0-3+) and percentage of immunoreactive tumor cells (0%-100%). BRAF VE1 immunoreactivity was determined using both lenient (≥1+, ≥1%) and stringent (≥2+, ≥10%) scoring criteria. Using lenient-scoring criteria, we found that the sensitivity and specificity of IHC compared with allele-specific real-time PCR were 100.0% and 18.2%, respectively. The poor specificity of lenient IHC analysis was attributable to weak, 1+ staining in both BRAF-mutated and wild-type LCH. Using stringent-scoring criteria, we found that specificity improved to 100.0% at the expense of sensitivity that decreased to 80.0%. Stringent scoring generated 3 false-negative results, but in all cases, neoplastic tissue comprised less than 5% of the stained section and/or the specimen was decalcified. In conclusion, highly sensitive molecular assays remain the gold standard for BRAF mutation analysis in LCH paraffin-embedded lesions. To avoid false-positive results, unequivocal VE1 staining of 2+ intensity in greater than or equal to 10% neoplastic histiocytes is required. However, negative VE1 results require additional studies to exclude false-negatives, and stringent-scoring criteria may not be optimal for scant or decalcified specimens.

Sino-Nasal Outcome Test-22 quality-of-life patterns in patients presenting with nasal septal perforation.

OBJECTIVES: To assess the impact of nasal septal perforation (NSP) on quality of life. DESIGN: Retrospective cohort study. SETTING: Rhinology clinics from two hospitals in Liverpool, United Kingdom. PARTICIPANTS: Patients diagnosed with NSP. MAIN OUTCOME MEASURES: Patients (n = 26) diagnosed with NSP completed the Sino-Nasal Outcome Test-22 (SNOT-22). The collated data were compared with SNOT-22 scores from a cohort of healthy volunteers (n = 34) and a cohort of patients (n = 30) diagnosed with chronic rhinosinusitis (CRS). RESULTS: The mean total SNOT-22 score of NSP and CRS cohorts was higher than that observed in healthy volunteers. The mean total SNOT-22 score in the CRS cohort (57.2, standard deviation SD 10.3) was the higher than NSP (50.2, SD 23.5), although this difference did not achieve statistical significance. The mean score for the rhinologic-specific domains (rhinologic symptoms, extranasal rhinologic symptoms), ear/facial symptoms and psychological dysfunction domain was higher in the CRS cohort compared to NSP, although statistical significance was only observed in the extranasal rhinologic symptoms domain (11.2, SD 2.4 vs 6.4, SD 4.1). Conversely, the mean sleep dysfunction domain score for NSP (12.7, SD 7.5) was higher than CRS (10.0, SD 4.9, respectively) although this was not statistically significant. CONCLUSIONS: This study has assessed the clinimetric and psychometric properties of patients suffering from symptomatic NSP. Future reports should consider inclusion of SNOT-22 data but with the addition of perforation-specific symptoms (nasal crusting, epistaxis, whistling noise).

Postoperative cognitive dysfunction and dementia: what we need to know and do.

Approximately 12% of apparently previously cognitively well patients undergoing anaesthesia and noncardiac surgery will develop symptoms of cognitive dysfunction after their procedure. Recent articles in this Journal have highlighted the difficulties of confirming any clear links between anaesthesia and cognitive dysfunction, in part because of the lack of consistency regarding definition and diagnosis. Postoperative cognitive dysfunction (POCD) is usually self-limiting and rarely persists in the longer term, although plausible biological mechanisms for an impact on brain protein deposition do exist. Clinical research studies are frequently confounded by a lack of agreed definitions and consistency of testing. Preoperative assessment of neurocognitive function and risk factor identification is imperative in order to ascertain the true extent of POCD and any causative link to anaesthesia and surgery. At present a multidisciplinary care bundle approach to risk factor stratification and reduction is the most attractive management plan based on evidence of slight benefit from individual interventions. As yet no individual anaesthetic technique, drug or mode of monitoring has been proved to reduce the incidence of POCD. Providing patients with appropriate and accurate information can be difficult because of conflicting evidence. The Royal College of Anaesthetists' patient liaison group has produced a useful patient information leaflet that is designed to provide guidance in discussions of individual risks whilst considerable uncertainties remain.

Themes arising in clinical consultation for therapists implementing family-based treatment for adolescents with anorexia nervosa: a qualitative study.

BACKGROUND: Our study aims to explore and describe themes arising in sessions of clinical consultation with therapists implementing Family-Based Treatment (FBT) for adolescents with Anorexia Nervosa (AN). There is currently no literature describing the content of clinical consultation for FBT. Thus, this knowledge will add to the evidence-base on what therapists need from consultants in ongoing clinical consultation. METHODS: Eight therapists at four sites participated in this study, which spanned a two-year period. Following a two-day training workshop, each therapist treated at least one adolescent patient presenting with a restrictive eating disorder with FBT, focusing on adherence to the treatment manual. Clinical consultation sessions occurred monthly and were led by an external FBT expert. Thirty-five (average per site = 9) audio recorded group clinical consultation sessions were transcribed verbatim and coded for themes. Twenty percent of the transcripts were double-coded to ensure consistency. Fundamental qualitative description guided the sampling and data collection. RESULTS: Thematic content analysis revealed ten common themes relating to the provision of clinical consultation to therapists implementing FBT in clinical practice: encouraging parental meal time supervision,discussing the role of mothers, how to align parents, ensuring parental buy-in, when to transition to Phase 2, weighing the patient and the patients' knowledge of their weight, the role of siblings in FBT sessions, how best to manage patient co-morbidities, the role of the father in FBT and how best to manage the family meal. CONCLUSIONS: In conclusion, clinical consultation themes aligned with many of the central tenets of FBT, including how to help parents align their supportive approach during the refeeding process, and how to help parents assume control of eating disordered behaviours. This knowledge helps to guide consultants to anticipate common issues brought forward by therapists attempting to implement FBT.

Histopathologic Characteristics of Intestinal Biopsy Samples from Dogs With Chronic Inflammatory Enteropathy With and Without Hypoalbuminemia.

BACKGROUND: Previous studies have identified hypoalbuminemia as a risk factor for negative outcome in dogs with chronic enteropathy (CE), but it has not been determined whether histopathology differs between CE dogs with and without hypoalbuminemia. OBJECTIVE: To compare histopathologic findings in dogs with biopsy-diagnosed inflammatory CE with and without hypoalbuminemia. ANIMALS: 83 dogs that had intestinal biopsy performed between January 2010-July 2015. Dogs had signs compatible with CE of at least 3-weeks' duration and no evidence of clinically relevant extra-gastrointestinal (GI) disease or potential non-GI causes of hypoalbuminemia. Dogs had primary diagnosis of inflammatory enteritis based on histopathology. METHODS: Dogs were grouped into CE with normoalbuminemia (CEN; serum albumin concentration ≥3.0 g/dL, N = 46) or chronic enteropathy with hypoalbuminemia (CEH; serum albumin concentration <3.0 g/dL, N = 37). A pathologist (SLP) blinded to the groups reviewed biopsy samples and applied the World Small Animal Veterinary Association scoring system to all samples. RESULTS: Intestinal biopsy samples from dogs in the CEH group were significantly more likely to display villous stunting, epithelial injury, crypt distension, and lacteal dilatation, and were more likely to have intraepithelial lymphocytes and lamina propria neutrophils than biopsy samples from dogs in the CEN group. Additionally, higher scores for each of the above listed histopathologic criteria were associated with a lower serum albumin concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathologic features of chronic inflammatory enteropathy differ between dogs that are hypo- versus normoalbuminemic. Additional work is needed to elucidate the clinical relevance of these differences.

Cardiovascular risk assessment in women - an update.

Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Although it is a disease of aging, vascular disease initiates much earlier in life. Thus, there is a need to be aware of the potential to prevent the development of the disease from an early age and continue this surveillance throughout life. The menopausal period and early menopause present an ideal opportunity to assess cardiovascular risk and plan accordingly. Generally in this period, women will be seen by primary health-care professionals and non-cardiovascular specialists. This review addresses female-specific risk factors that may contribute to the potential development of cardiovascular disease. It is important for all health-care professionals dealing with women in midlife and beyond to be cognisant of these risk factors and to initiate female-specific preventative measures or to refer to a cardiovascular specialist.

Giraffe genome sequence reveals clues to its unique morphology and physiology.

The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions.

Desiccation survival time for eggs of a widespread and invasive Australian mosquito species, Aedes (Finlaya) notoscriptus (Skuse).

The Australian native mosquito Aedes (Finlaya) notoscriptus (Skuse) is closely associated with natural and artificial water holding receptacles. Eggs are laid in habitats where they are exposed to drying conditions as water levels fluctuate. Withstanding desiccation enables survival in challenging environments and increases the potential for establishment in non-native habitats. Until now, the desiccation resistance of Ae. notoscriptus eggs has been unknown despite the historical invasive success of this important dog heartworm and arbovirus vector. Viability and mean survival times of eggs from two Ae. notoscriptus populations (metropolitan areas of Sydney, NSW and Adelaide, SA) were evaluated, with eggs stored under three dryness conditions for up to 367 days. Our results revealed that Ae. notoscriptus eggs can withstand desiccation for extended periods, under a variety of conditions, with approximately 9-13% egg viability recorded after one year. This prolonged egg survival reflects the widespread distribution of this mosquito in Australia and its history of incursions and subsequent establishment in non-native habitats. Differences in mean egg volume were recorded in addition to significantly different egg length to width ratios for the two populations, which may reflect adaptation to biotope of origin and an associated likelihood of drought and drying conditions. The results of this study suggest that the desiccation resistant eggs of Ae. notoscriptus make this species highly adaptable, increasing the risk of movement to non-endemic regions of the world.

The complete mitochondrial DNA genomes for two lineages of Aedes notoscriptus (Diptera: Culicidae).

The complete mitochondrial genomes for two deeply divergent lineages of the urban adapted mosquito Aedes notoscriptus Skuse (Diptera: Culicidae) in Australia were sequenced using a combination of next generation Illumina and traditional Sanger sequencing. The 15,846 and 15,851 bp circular genomes share 95.0% nucleotide identity. They both have the full complement of 37 metazoan genes and identical gene arrangements to previously published Culicidae species with the one non-coding A + T rich control region present between rns and tRNA-Ile. All protein initiation codons are ATN apart from COX1 (TCG). Eight protein coding genes encode full TAA stop codons, one uses an incomplete TA and four use T. Typical cloverleaf structures containing DHU and TΨC stem and loops can be inferred for all 22 tRNAs.