Retaining dermatology patients in primary care through dialogue with secondary care providers: A service evaluation.

BACKGROUND: There are long patient waiting lists for specialist care. A dermatology dialogue service between primary and secondary care (DDPS) was developed in eastern England. Primary care referrers uploaded patient images of skin conditions for review by and dialogue with consultant dermatologists in an attempt to retain patients in primary care rather than refer them to secondary care. METHODS: Evaluation of service performance against specific targets, including reduction in secondary care waiting list growth over the period April 2021-March 2022 inclusive. Service activity was summarized in terms of speed of resolution, case numbers, and dispositions. Clinician and patient satisfaction were assessed using structured questionnaires. Actual numbers of new referrals were compared to projections based on historical data. Waiting list growth was compared to other specialties and other commissioning areas. Waiting times to initial treatment were monitored. RESULTS: Over 3300 patients were enrolled and > 90% of dialogues were resolved within 36 hours. Clinician and patient satisfaction were high. Frequently asked questions and conditions were highlighted by dermatologists to design and deliver an educational event for primary care clinicians that was well received. Waiting list growth for dermatology patients in the commissioning area was smaller than for other major specialties, and generally smaller than growth for dermatology waiting lists commissioned by other NHS commissioners. There was no negative impact on the urgent priority (cancer pathway) waiting list. CONCLUSION: The DDPS was satisfactory for clinicians and patients and coincided with lower growth in dermatology waiting lists than might otherwise have been expected.

Variable but not random: temporal pattern coding in a songbird brain area necessary for song modification.

Practice of a complex motor gesture involves motor exploration to attain a better match to target, but little is known about the neural code for such exploration. We examine spiking in a premotor area of the songbird brain critical for song modification and quantify correlations between spiking and time in the motor sequence. While isolated spikes code for time in song during performance of song to a female bird, extended strings of spiking and silence, particularly bursts, code for time in song during undirected (solo) singing, or "practice." Bursts code for particular times in song with more information than individual spikes, and this spike-spike synergy is significantly higher during undirected singing. The observed pattern information cannot be accounted for by a Poisson model with a matched time-varying rate, indicating that the precise timing of spikes in both bursts in undirected singing and isolated spikes in directed singing code for song with a temporal code. Temporal coding during practice supports the hypothesis that lateral magnocellular nucleus of the anterior nidopallium neurons actively guide song modification at local instances in time.NEW & NOTEWORTHY This paper shows that bursts of spikes in the songbird brain during practice carry information about the output motor pattern. The brain's code for song changes with social context, in performance versus practice. Synergistic combinations of spiking and silence code for time in the bird's song. This is one of the first uses of information theory to quantify neural information about a motor output. This activity may guide changes to the song.

A systematic scoping review of early interventions for parents of deaf infants.

BACKGROUND: Over 90% of the 50,000 deaf children in the UK have hearing parents, many of whom were not expecting a deaf child and may require specialist support. Deaf children can experience poorer long-term outcomes than hearing children across a range of domains. After early detection by the Universal Newborn Hearing Screening Programme, parents in the UK receive support from Qualified Teachers of the Deaf and audiologists but resources are tight and intervention support can vary by locality. There are challenges faced due to a lack of clarity around what specific parenting support interventions are most helpful. METHODS: The aim of this research was to complete a systematic scoping review of the evidence to identify early support interventions for parents of deaf infants. From 5577 identified records, 54 met inclusion criteria. Two reviewers screened papers through three rounds before completing data extraction and quality assessment. RESULTS: Identified parent support interventions included both group and individual sessions in various settings (including online). They were led by a range of professionals and targeted various outcomes. Internationally there were only five randomised controlled trials. Other designs included non-randomised comparison groups, pre / post and other designs e.g. longitudinal, qualitative and case studies. Quality assessment showed few high quality studies with most having some concerns over risk of bias. CONCLUSION: Interventions commonly focused on infant language and communication followed by parental knowledge and skills; parent wellbeing and empowerment; and parent/child relationship. There were no interventions that focused specifically on parent support to understand or nurture child socio-emotional development despite this being a well-established area of poor outcome for deaf children. There were few UK studies and research generally was not of high quality. Many studies were not recent and so not in the context of recent healthcare advances. Further research in this area is urgently needed to help develop evidence based early interventions.

Impact of reduced-representation sequencing protocols on detecting population structure in a threatened marsupial.

Reduced-representation sequencing methods have wide utility in conservation genetics of non-model species. Several methods are now available that reduce genome complexity to examine a wide range of markers in a large number of individuals. We produced two datasets collected using different laboratory techniques, comprising a common set of samples from the greater bilby (Macrotis lagotis). We examined the impact of differing data filtering thresholds on downstream population inferences. We found that choice of restriction enzyme and data filtering thresholds, especially the rate of allowable missing data, impacted our ability to detect population structure. Estimates of FST were robust to alterations in laboratory and bioinformatic protocols while principal coordinates and STRUCTURE analyses showed variation according to the number of loci and percent missing data. We advise researchers using reduced-representation sequencing in conservation projects to examine a range of data thresholds, and follow these through to downstream population inferences. Multiple measures of population differentiation should be used in order to fully understand how data filtering thresholds influence the final dataset, paying particular attention to the impact of allowable missing data. Our results indicate that failure to follow these checks could impact conclusions drawn, and conservation management decisions made.

A Tasmanian devil breeding program to support wild recovery.

Tasmanian devils are threatened in the wild by devil facial tumour disease: a transmissible cancer with a high fatality rate. In response, the Save the Tasmanian Devil Program (STDP) established an 'insurance population' to enable the preservation of genetic diversity and natural behaviours of devils. This breeding program includes a range of institutions and facilities, from zoo-based intensive enclosures to larger, more natural environments, and a strategic approach has been required to capture and maintain genetic diversity, natural behaviours and to ensure reproductive success. Laboratory-based research, particularly genetics, in tandem with adaptive management has helped the STDP reach its goals, and has directly contributed to the conservation of the species in the wild. Here we review this work and show that the Tasmanian devil breeding program is a powerful example of how genetic research can be used to understand and improve reproductive success in a threatened species.

Reaching rural veterans: a new mechanism to connect rural, low-income US Veterans with resources and improve food security.

BACKGROUND: Rural, low-income US veterans face additional barriers to accessing food and resources compared to urban veterans. Based on both social-ecological and cultural competence approaches, the Reaching Rural Veterans (RRV) pilot intervention built on the existing infrastructure of food pantries to improve food security and connect rural, low-income veterans with resources. This article describes the process of implementing and evaluating RRV. METHODS: Five rural food pantries within each of two states, Indiana and Kentucky, received training in cultural competence and held monthly outreach events where food and services were offered to veterans. Veteran adult participants completed an assessment at baseline and 3-month follow-up that measured food security using the US Household Food Security Survey Module and self-reported resource enrollment. Repeated measures logistic regression models evaluated the odds of improving food security and resource enrollment from baseline to follow-up (significance P < 0.05). RESULTS: RRV recruited 234 participants; 53% completed the follow-up assessment. At follow-up, the odds of household (P = 0.009) and adult (P = 0.01) food security increased, as did enrollment in one or more of the following resources: Temporary Assistance for Needy Families, Supplemental Security Income, General Assistance or Assistance from the Township Trustee (P = 0.005). CONCLUSIONS: RRV yielded promising preliminary results of improved food security and resource use.

Normalized serum eosinophil peroxidase levels are inversely correlated with esophageal eosinophilia in eosinophilic esophagitis.

Eosinophil peroxidase is an eosinophil-specific, cytoplasmic protein stored in the secondary granules of eosinophils. While eosinophil peroxidase deposition is increased in the esophagus in eosinophilic esophagitis (EOE), its potential role as a peripheral marker is unknown. This study aims to examine the relationship between serum eosinophil peroxidase and esophageal eosinophilia in eosinophilic esophagitis. Prospectively collected serum from 19 subjects with incident EoE prior to treatment and 20 non-EoE controls were tested for serum eosinophil peroxidase, eosinophilic cationic protein, and eosinophil derived neurotoxin using ELISA. Matching esophageal tissue sections were stained and assessed for eosinophil peroxidase deposition using a histopathologic scoring algorithm. Mean peripheral blood absolute eosinophil counts in eosinophilic esophagitis subjects were significantly elevated compared to controls (363 vs. 195 cells/µL, P = 0.008). Absolute median serum eosinophil peroxidase, eosinophil cationic protein, and eosinophil derived neurotoxin did not differ between groups; however, when normalized for absolute eosinophil counts, eosinophilic esophagitis subjects had significantly lower median eosinophil peroxidase levels (2.56 vs. 6.96 ng/mL per eos/µL, P = 0.002, AUC 0.79 (0.64, 0.94 95% CI)). Multivariate analysis demonstrated this relationship persisted after controlling for atopy. Esophageal biopsies from eosinophilic esophagitis subjects demonstrated marked eosinophil peroxidase deposition (median score 46 vs. 0, P < 0.0001). Normalized eosinophil peroxidase levels inversely correlated with esophageal eosinophil density (r = -0.41, P = 0.009). In contrast to marked tissue eosinophil degranulation, circulating eosinophils appear to retain their granule proteins in EoE. Investigations of normalized serum eosinophil peroxidase levels as a biomarker of EoE are ongoing.

Self-assessment of ergonomics amongst dental students utilising photography: RCT.

INTRODUCTION: Dental professionals are at high risk of musculoskeletal disorders (MSDs) due to static working positions for extended periods of time. Musculoskeletal pain has been identified as early as during their entry-level dental education. The purpose of this study was to determine whether feedback involving photography and self-assessment would improve ergonomic scores and the accuracy of ergonomic self-assessments amongst dental students. MATERIALS AND METHODS: The study involved a randomised control design of 135 dental students. At weeks 1 and 4, participants were photographed, and at weeks 1 through 4, participants completed ergonomic self-evaluations, using a Modified-Dental Operator Posture Assessment Instrument (M-DOPAI). During weeks 2 and 3, participants in the training group were photographed and used those photographs to complete ergonomic self-assessments. All participants' pre-training and post-training photographs were evaluated for ergonomic scores by two raters. RESULTS: A mixed-design ANOVA of ergonomic scores revealed that ergonomic scores improved for all students who received the ergonomics training (F(1,254)=17.41, P < .001). In addition, a mixed-design ANOVA of kappa coefficient values between student and rater scores revealed that the accuracy of self-assessments improved for all students who received the ergonomics training (F(1,127)=6.33, P < .05). CONCLUSION: The use of photographs and self-assessment provides dental and dental hygiene educators with a pragmatic method to improve self-assessment skills, increase student awareness of any postural deviations from ideal and improve musculoskeletal health.

Deprivation and healthy food access, cost and availability: a cross-sectional study.

BACKGROUND: Food access, cost and availability have been identified as determinants of dietary choice. It has been suggested that these are socio-economically patterned; however, the evidence is inconclusive. The present study investigated whether differences exist with respect to healthy food access, cost and availability between areas of contrasting deprivation. METHODS: An ecological, cross-sectional study was conducted in two of the most and two of the least deprived wards in Plymouth. Food retail outlets (FROs) (n = 38) were identified and mapped using Geographic Information Systems to assess 'physical access', by foot, to food retail provision. Healthy food basket (HFB) surveys were conducted (n = 32) to compare the cost and availability of 28 healthy food items between the more and less deprived areas. RESULTS: Areas of poor access to food retail provision were identified in both study areas, with a higher number of households in the more-deprived areas being affected than in the less-deprived areas, after accounting for car ownership levels. Median [IQR] HFB availability was lower in more-deprived than the less-deprived areas (48%, [39-71%] vs. 75%, [68-82%]; P=0.003), and in convenience stores than supermarkets (54%, [43-72%] vs. 78%, [72-96%]; P=0.001). Descriptive summaries revealed negligible differences in total median HFB cost between the more-deprived and less-deprived areas (£55.97 versus £55.94) and a larger cost difference between convenience stores and supermarkets (£62.39 versus £44.25). CONCLUSIONS: Differences were found with respect to healthy food access, cost and availability in areas of contrasting deprivation. These appeared to be related to FRO type rather than deprivation alone.

'I can't tell my child they are dying'. Helping parents have conversations with their child.

This paper explores the challenges of resolving conflicting feelings around talking with a child about their terminal prognosis. When children are left out of such conversations it is usually done with good intent, with a parent wishing to protect their child from anxiety or loss of hope. There is however growing evidence that sensitive, timely, age appropriate information from those with whom children have a good relationship is helpful both for the child and their family. There is no evidence that involving children in sensitive and timely discussions creates significant problems, rather that withholding information may lead to confusion, frustration, distress and anger. The authors discuss ways in which families can be supported to have these significant conversations with their children.

Variability in the anterior extralaryngeal branch of the recurrent laryngeal nerve: clinical implications.

BACKGROUND: This study aimed to identify the anterior and posterior extralaryngeal branches (AELB, PELB) of the recurrent laryngeal nerve (RLN), measure these branches when present, and determine relationships between gender, sidedness and neck length. MATERIALS AND METHODS: Dissection was completed to level of the thyroid on 45 cadavers. The course of the RLN was then traced superiorly from its entry into the neck. Careful reflection of the thyroid and dissection of the lateral thyroid ligament permitted visualisation of the full course of the nerve. If extralaryngeal branching (ELB) was present, measurements were taken from the point of bifurcation of the RLN to the point of laryngeal entry through the cricothyroid membrane. Neck measurements, from the spinous process of C7 to the superior nuchal line, were taken. Gender of the specimen was noted. Data was analysed in SPSS. RESULTS: Extralaryngeal branching was found in 77.78% of our sample, 77.14% on the left and 54.29% on the right. A significant difference was found between AELB length on the left and right, indicating that the left branch will be longer than the right when present. A significant difference in neck length between those with and without ELB was also found, indicating that people with longer necks more often display ELB. Neither neck length and AELB length, nor gender and AELB length were strongly correlated in this sample. CONCLUSIONS: Extralaryngeal branching can occur in all populations, but there are definite trends in its incidence and length. Surgeons should be aware of these trends before operating on patients.

Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness.

BACKGROUND: In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. METHODS: Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP® . Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. RESULTS: No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively). CONCLUSIONS: Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.

An unusual presentation of juvenile systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disorder with a diverse spectrum of clinical abnormality. Despite advances in our understanding of the disease, the aetiology and outcome remains unknown. We describe a 13-year-old boy who presented with paronychia, mouth ulcers and associated neutropenia. Appropriate investigations including a bone-marrow biopsy revealed a shift to the left, and in the absence of any other immunological abnormalities, a diagnosis of idiopathic neutropenia was made. The patient was successfully treated with granulocyte colony-stimulating factor but subsequently re-presented during the winter months with a purpuric facial eruption affecting his cheeks and ears. On histological examination of a biopsy taken from the ear, a microvascular thrombosis was seen. Laboratory investigations were positive for anticardiolipin antibodies, neutropenia and antinuclear antibodies (ANA), suggesting a diagnosis of juvenile (J)JSLE with antiphospholipid syndrome. This is an unusual presentation of SLE in a prepubertal white boy, with a malar and helical vasculopathy as a novel cutaneous presentation of JSLE.

Effects of isometric resistance training and detraining on ambulatory blood pressure and morning blood pressure surge in young normotensives.

Isometric resistance training (IRT) has been shown to reduce resting and ambulatory blood pressure (BP), as well as BP variability and morning BP surge (MBPS). However, there are no data available regarding how long after cessation of IRT these effects are maintained. Therefore, the purpose of this study was to determine the effects of 8 weeks of detraining on resting BP, ambulatory BP and MBPS following 8 weeks of IRT in a population of young normotensive individuals and to further substantiate previously reported reductions in MBPS following IRT. Twenty-five apparently healthy participants with resting BP within the normal range (16 men, age = 23 ± 6 years; 9 women, age = 22 ± 4 years, resting BP: 123 ± 5/69 ± 7 mmHg) were randomly assigned to a training-detraining (TRA-DT, n = 13) or control (CON, n = 12) group. Resting BP, ambulatory BP and MBPS were measured prior to, after 8 weeks of bilateral leg IRT using an isokinetic dynamometer (4 × 2-min contractions at 20% MVC with 2-min rest periods, 3 days/week) and following an 8-week detraining period. There were significant reductions in 24-h ambulatory systolic BP (SBP) and calculated SBP average real variability (ARV) following IRT that were maintained after detraining (pre-to-post detraining, -6 ± 4 mmHg, p = 0.008, -2 ± 1.5 mmHg, p = 0.001). Similarly, the training-induced decreases in daytime SBP and daytime SBP ARV (pre-to-post detraining, -5 ± 6 mmHg, p = 0.001; -2 ± 1.2 mmHg, p = 0.001, respectively), MBPS (pre-to-post detraining, -6 ± 9 mmHg, p = 0.046) and resting SBP (pre-to-post detraining, -4 ± 6 mmHg, p = 0.044) were preserved. There were no changes in night-time or night-time SBP ARV across all time points (pre-to-post detraining, -1 ± 8 mmHg, p = 1.00, -0.7 ± 2.9 mmHg, p = 1.00). These results confirm that IRT causes significant reductions in resting BP, ambulatory BP, ambulatory ARV and MBPS. Importantly, the changes remained significantly lower than baseline for 8 weeks after cessation of training, suggesting a sustained effect of IRT.

The effect of the COVID-19 pandemic on non-elective otolaryngology admissions and a positive change in clinical practice.

As the COVID-19 pandemic progressed across the UK and Northern Ireland in March 2020, our otolaryngology department began to make preparations and changes in practice to accommodate for potentially large numbers of patients with COVID-19 related respiratory illness in the hospital. We retrospectively reviewed the number of non-elective admissions to our department between the months of January and May in 2019 and 2020. A significant reduction in admissions of up to 94% during the months of the pandemic was observed. Our practice shifted to manage patients with epistaxis and peritonsillar abscess on an outpatient basis, and while prospectively collecting data on this, we did not observe any significant adverse events. We view this as a positive learning point and change in our practice as a result of the COVID-19 pandemic.

Change in a clinical measure of cervical movement sense following four weeks of kinematic training.

BACKGROUND: Training targeted towards improving cervical movement accuracy is an effective strategy in the management of neck pain. Relatively complex measures have been validated to measure this in research although a simple clinical measure using a head mounted laser tracing a standardised pattern has been shown to be reliable. It is not known if this method demonstrate clinically meaningful change to training. OBJECTIVE: To assess change responsiveness of the clinical cervical movement sense (CCMS) test following home kinematic training (KT). STUDY DESIGN: Pre-post treatment observational study. METHODS: The CCMS measure was assessed in 56 patients with chronic neck pain (41 intervention, 15 control) at baseline and 4 weeks post intervention by blinded assessors. Task completion time and error number were assessed reviewing video of the performances. Change pre-post intervention was compared between groups. RESULTS: There was a significantly greater mean improvement in the intervention (-9.2 ± 9.3) seconds) for completion time and combined time and error (-13.3 ± 16) compared to the control group for time (-2.0 ± 9.8) and combined time and error (-1.8 ± 14) with moderate to high effect sizes (Cohen's d 0.76). There was a non-significant trend for decreased number of errors in the intervention (-4.1 ± 9.0) compared to control group (0.2 ± 8.3). CONCLUSION: Completion time of the CCMS test appears to be able to demonstrate meaningful change following four weeks of KT. This further supports its clinical utility as a measure of cervical movement accuracy and provides direction for future clinical use.

Lagniappes: "A Little Something Extra" or Unintended Positive Consequences of Implementation Facilitation.

OBJECTIVE: Implementation facilitation is an effective strategy that increases uptake of behavioral health interventions. Facilitation is grounded in partnerships with leadership and clinical stakeholders. Researchers have documented some negative consequences of facilitation-time, financial, and opportunity costs. Clinical leaders often agree to facilitation with the promise of increased implementation of an intervention. This study examined whether unintended positive consequences of facilitation might offset known costs. METHODS: This study was part of a stepped-wedge, hybrid type 2, pragmatic trial that used implementation facilitation to implement primary care mental health integration (PCMHI) via telehealth technology in six satellite Veterans Health Administration (VHA) clinics. Two facilitators provided facilitation for at least 6 months. This study included a focused analysis of an emerging phenomenon captured through weekly debriefing interviews with facilitators: unintended positive consequences of implementation facilitation, termed "lagniappes" here. A rapid content analysis was conducted to identify and categorize these consequences. RESULTS: The authors documented unintended positive consequences of the facilitation across the six VHA sites and categorized them into three clinically relevant domains: supporting PCMHI outreach at other clinics not in the original catchment area (e.g., providing tools to other sites), strengthening patient access (e.g., resolving unnecessary patient travel), and improving or modifying work processes (e.g., clarifying suicide assessment protocols). The positive consequences benefited sites and strengthened ongoing partnerships. CONCLUSIONS: Documenting unintended positive consequences of implementation facilitation may increase leadership engagement. Facilitators should consider leveraging unintended positive consequences as advantages for the site that may add efficiency to facility processes and workflows.

Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytes.

PURPOSE: Human remyelination promoting IgM mAbs target oligodendrocytes (OLs) and function in animal models of multiple sclerosis (MS). However, their mechanism of action is unknown. This study seeks to identify the cellular mechanism of action of a recombinant human IgM on OL survival. METHODS: Binding of rHIgM22 to the surface of rat OLs was studied by co-localization with various markers. RHIgM22-mediated effects on apoptotic signaling in OLs, differentiation markers, and signaling molecules were detected by Western blotting and immunoprecipitation. RESULTS: RHIgM22 co-localized with integrin ß3 but not other integrin ß-chains in OLs. Downstream of integrin ß3 we identified Src family kinase (SFK) Lyn as a key player of rHIgM22-mediated actions in OLs. Lyn immunoprecipitated in a complex together with integrin αvß3 and PDGFαR. Lyn expression was 9-fold up-regulated and Lyn activation was 3-fold higher inrHIgM22-treated OL cultures compared with controls. RHIgM22 inhibited apoptotic signaling by greater than 10-fold reduction of caspase-3 and capsase-9 cleavage and reduced by 4-fold expression of differentiation markers MBP and MOG in OLs. SFK inhibitors PP2 and SU6656 inhibited Lyn activity and restored caspase-cleavage in OLs. A human IgM that did not promote remyelination and medium wereused as controls. CONCLUSIONS: rHIgM22 prevented apoptotic signaling andinhibited OL differentiation by Lyn implying thatIgM-mediated remyelination is due toprotection of OPC and OLs rather than promotion of OPC differentiation.

Humoral immune responses in CD40 ligand-deficient mice.

Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mice exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages of B and T cell subpopulations. CD40L-deficient mice did display selective deficiencies in humoral immunity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-deficient mice failed to mount secondary antigen-specific responses to immunization with a thymus-dependent antigen, trinitrophenol-conjugated keyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient mice produced antigen-specific antibody of all isotypes except IgE in response to the thymus-independent antigen, DNP-Ficoll. These results underscore the requirement of CD40L for T cell-dependent antibody responses. Moreover, Ig class switching to isotypes other than IgE can occur in vivo in the absence of CD40L, supporting the notion that alternative B cell signaling pathways regulate responses to thymus-independent antigens.

BioWeld(®) Tube and surgical glue for experimental sutureless venous microanastomosis.

BACKGROUND: The medial wall of mammalian veins is generally thin and fragile compared with the thick muscle seen in arteries. This makes venous microanastomoses time consuming and challenging. This study aimed to determine the feasibility and effectiveness of using the BioWeld(®) Tube in conjunction with a surgical glue (butyl-2-cyanoacrylate) in performing sutureless venous microanastomoses. METHODS: The feasibility and effectiveness of microvascular anastomoses in a rabbit jugular vein model were investigated in six animals, using the BioWeld(®) Tube in conjunction with butyl-2-cyanoacrylate surgical glue. Patency and tissue repair mechanisms at the anastomotic site were assessed 1 week after the procedure. RESULTS: All anastomoses remained patent at 1 week. Muscle necrosis occurred only in areas where the tissue was subject to the fold-and-bond procedure. CONCLUSION: The study showed the feasibility and short-term effectiveness of the BioWeld(®) Tube in facilitating venous anastomoses.