Animated teaching improves student learning of human gastrulation and neurulation.

Human embryology is a complex topic that brings together core components of anatomy and physiology to describe the developmental process from fertilisation to birth. Embryonic development is a challenging topic of study that is core to the curricula for health science students. There are challenges ingrained in teaching and learning embryology, due to the three-dimensional dynamic processes that occur as the embryo develops. This study aimed to develop and assess two newly developed animations depicting key processes in embryology, namely gastrulation and neurulation, as supplemental learning aids for students. Indeed, animated teaching tools to enhance the learning of gastrulation and neurulation are not widely available. A multi-disciplinary team of physiologists, biochemists, anatomists, and a computer scientist developed the animation sets. A student cohort of 81 first-year health science students were enrolled in this study over a period of three academic years. Both animations are in line with the course content of the first-year health science students undertaking the Human Health and Disease BSc at Trinity College Dublin, who were the study participants. Participants were randomly assigned to a non-animation control group and an animation group. Each set of animated teaching aids was broken down into individual clips which were given identifiable headings to allow the user to interchange between clips to facilitate a more personal learning experience. The animation group had open access to the animations for a three-week period. Questionnaires were designed to assess participants' attitude to the animations and their knowledge of embryology, both at the start of the study and three weeks later following access to the animations. Data presented herein indicate that students incorporated the animated teaching aids into digital home study and that the use of the animations acted as a supplemental tool that increased student knowledge in key areas of human embryology. From a qualitative point of view, students described the animations as enjoyable and helpful in visualising complex processes. This study indicates that the development of gastrulation and neurulation animated learning tools allow for a more engaging learning experience, facilitating student's engagement with academically challenging concepts in human embryology.

Systematic review of the efficacy, effectiveness and safety of MF59® adjuvanted seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of MF59® adjuvanted trivalent and quadrivalent influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions (NRSIs) were eligible for inclusion. The search returned 28,846 records, of which 48 studies on MF59® adjuvanted vaccines met our inclusion criteria. No efficacy trials were identified. In terms of vaccine effectiveness (VE), MF59® adjuvanted trivalent influenza vaccines were effective in preventing laboratory-confirmed influenza in older adults (aged ≥65 years) compared with no vaccination (VE = 45%, 95% confidence interval (CI) 23%-61%, 5 NRSIs across 3 influenza seasons). By subtype, significant effect was found for influenza A(H1N1) (VE = 61%, 95% CI 44%-73%) and B (VE = 29%, 95% CI 5%-46%), but not for A(H3N2). In terms of relative VE, there was no significant difference comparing MF59® adjuvanted trivalent vaccines with either non-adjuvanted trivalent or quadrivalent vaccines. Compared with traditional trivalent influenza vaccines, MF59® adjuvanted trivalent influenza vaccines were associated with a greater number of local adverse events (RR = 1.90, 95% CI 1.50-2.39) and systemic reactions (RR = 1.18, 95% CI 1.02-1.38). In conclusion, MF59® adjuvanted trivalent influenza vaccines were found to be more effective than 'no vaccination'. Based on limited data, there was no significant difference comparing the effectiveness of MF59® adjuvanted vaccines with their non-adjuvanted counterparts.

Systematic review of the efficacy, effectiveness and safety of recombinant haemagglutinin seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of recombinant haemagglutinin (HA) seasonal influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions were eligible for inclusion. The search returned 28,846 records, of which 10 studies on recombinant HA influenza vaccine met our inclusion criteria. One study found that the quadrivalent recombinant HA influenza vaccine had higher relative vaccine efficacy (rVE) in preventing laboratory-confirmed influenza during the 2014-15 season compared with traditional quadrivalent vaccination in adults aged ≥50 years (rVE = 30%, 95% CI 10%-47%, moderate-certainty evidence). In a subgroup analysis, higher rVE was reported for influenza A (rVE = 36%, 95% CI 14% to 53%), but not for B (non-significant). Another study reported higher efficacy for the trivalent recombinant HA vaccine compared with placebo (VE = 45%, 95% CI 19-63, 1 RCT, low-certainty evidence) in adults aged 18-55 years. With the exception of a higher rate of chills (RR = 1.33, 95% CI 1.03-1.72), the safety profile of recombinant HA vaccines was comparable to that of traditional influenza vaccines. The evidence base for the efficacy and effectiveness of recombinant HA influenza vaccines is limited at present, although one study found that the quadrivalent recombinant HA influenza vaccine had higher rVE compared with traditional quadrivalent vaccination in adults aged ≥50 years.

Systematic review of the efficacy, effectiveness and safety of high-dose seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

This review sought to assess the efficacy, effectiveness and safety of high-dose inactivated influenza vaccines (HD-IIV) for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD-IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard-dose influenza vaccines (SD-IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10-37, one RCT). One NRSI demonstrated significant effect for HD-IIV3 against influenza B (VE = 89%, 95% CI 47-100), but not for influenza A(H3N2) (VE = 22%, 95% CI -82 to 66) when compared with no vaccination in older adults. HD-IIV3 showed significant relative effect compared with SD-IIV3 for influenza-related hospitalisation (VE = 11.8%, 95% CI 6.4-17.0, two NRSIs), influenza- or pneumonia-related hospitalisation (VE = 13.7%, 95% CI 9.5-17.7, three NRSIs), influenza-related hospital encounters (VE = 13.1%, 95% CI 8.4-17.7, five NRSIs), and influenza-related office visits (VE = 3.5%, 95% CI 1.5-5.5, two NRSIs). For safety, HD-IIV were associated with significantly higher rates of local and systemic adverse events compared with SD-IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD-IIV, HD-IIV were found to be more effective in the prevention of laboratory-confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events.

Systematic review of the efficacy, effectiveness and safety of cell-based seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through strain-specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell-based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full-text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell-based vaccines compared with traditional vaccines (egg-based). Efficacy data were available comparing cell-based trivalent influenza vaccines with placebo in adults (aged 18-49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%-77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%-89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%-87%, 2 RCTs) and 52% against influenza B (95% CI 30%-68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell-based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell-based vaccines for influenza-related hospitalisation, hospital encounters and physician office visits. The safety profile of cell-based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell-based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18-49 years. Overall cell-based vaccines are well-tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.

Cost-effectiveness of metabolic surgery for the treatment of type 2 diabetes and obesity: a systematic review of economic evaluations.

AIM: To systematically identify and appraise the international literature on the cost-effectiveness of metabolic surgery for the treatment of comorbid type 2 diabetes (T2D) and obesity. METHODS: A systematic search was conducted in electronic databases and grey literature sources up to 20 January 2021. Economic evaluations in a T2D population or a subpopulation with T2D were eligible for inclusion. Screening, data extraction, critical appraisal of methodological quality (Consensus Health Economic Criteria list) and assessment of transferability (International Society for Pharmacoeconomics and Outcomes Research questionnaire) were undertaken in duplicate. The incremental cost-effectiveness ratio (ICER) was the main outcome. Costs were reported in 2020 Irish Euro. Cost-effectiveness was interpreted using willingness-to-pay (WTP) thresholds of €20,000 and €45,000/quality-adjusted life year (QALY). Due to heterogeneity arising from various sources, a narrative synthesis was undertaken. RESULTS: Thirty studies across seventeen jurisdictions met the inclusion criteria; 16 specifically in a T2D population and 14 in a subpopulation with T2D. Overall, metabolic surgery was found to be cost-effective or cost-saving. Where undertaken, the results were robust to sensitivity and scenario analyses. Of the 30 studies included, 15 were considered high quality. Identified limitations included limited long-term follow-up data and uncertainty regarding the utility associated with T2D remission. CONCLUSION: Published high-quality studies suggest metabolic surgery is a cost-effective or cost-saving intervention. As the prevalence of obesity and obesity-related diseases increases worldwide, significant investment and careful consideration of the resource requirements needed for metabolic surgery programmes will be necessary to ensure that service provision is adequate to meet demand.

ADAPTE with modified Delphi supported developing a National Clinical Guideline: stratification of clinical risk in pregnancy.

OBJECTIVES: Adaptation has been proposed as an alternative to de novo development to take advantage of existing clinical guidelines (guidelines) and reduce duplication. We describe the process of incorporating a modified Delphi method to reach formal consensus and inform locally relevant clinical recommendations during the development, through the ADAPTE process, of the Irish National Clinical Guideline No. 23 Stratification of Clinical Risk in Pregnancy. METHODS: A systematic search of guideline repositories, websites, and bibliographic databases was conducted. Quality appraisal was undertaken using AGREE II. Risk factors indicating the need for additional care were identified and extracted from high-quality guidelines. A three-round modified Delphi panel comprising healthcare stakeholders, was convened to agree and tailor risk factors. RESULTS: Of seven relevant international guidelines identified, three were considered high quality and contained a combined 59 risk factors potentially suitable for adaptation. Following the three-round Delphi process, 49 risk factors were included in the final guideline. Excluded risk factors were generally considered to be too broad to be useful for the Irish context. CONCLUSION: We believe that a formal consensus technique included within the ADAPTE process increased the rigor and transparency of this process and ensured the inclusion of more locally relevant risk factors.

Missing Stories: Women with Physical Disabilities' Navigation and Responses to Domestic and Family Violence.

There is significant global evidence that highlights both the high rates of domestic and family violence (DFV) for women with disabilities and the challenges they can face when navigating and responding to DFV. The purpose of this study was to understand women with physical disabilities' experiences of help-seeking when they did not access generalist DFV services. Presented are the participants' lived experiences of navigating and responding to DFV. Key findings include how participants resisted ableism, challenged assumptions about passivity, and the impacts of this resistance on their navigation of DFV.

Challenges encountered during the systematic review of newer and enhanced influenza vaccines and recommendations for the future.

There are a variety of challenges in the conduct of systematic reviews of influenza vaccines. We describe our experience of completing four systematic reviews of newer and enhanced inactivated seasonal influenza vaccines. The reporting of the included studies created significant challenges for study identification, data extraction and analysis. Those challenges have implications for the resources required to conduct reviews and, more significantly, for the accuracy of the estimated treatment effect. There is a substantial burden of morbidity and mortality associated with seasonal influenza, and the evidence used to support vaccination strategies requires regular review. An improved review process will facilitate robust decision-making both nationally and internationally. We recommend the development of reporting guidelines, increased engagement between researchers and decision makers, a database of identified trials, and research into search optimisation.

Transmission of SARS-CoV-2 by children: a rapid review, 30 December 2019 to 10 August 2020.

BackgroundThe role of children in the transmission of SARS-CoV-2 during the early pandemic was unclear.AimWe aimed to review studies on the transmission of SARS-CoV-2 by children during the early pandemic.MethodsWe searched MEDLINE, Embase, the Cochrane Library, Europe PubMed Central and the preprint servers medRxiv and bioRxiv from 30 December 2019 to 10 August 2020. We assessed the quality of included studies using a series of questions adapted from related tools. We provide a narrative synthesis of the results.ResultsWe identified 28 studies from 17 countries. Ten of 19 studies on household and close contact transmission reported low rates of child-to-adult or child-to-child transmission. Six studies investigated transmission of SARS-CoV-2 in educational settings, with three studies reporting 183 cases from 14,003 close contacts who may have contracted COVID-19 from children index cases at their schools. Three mathematical modelling studies estimated that children were less likely to infect others than adults. All studies were of low to moderate quality.ConclusionsDuring the early pandemic, it appeared that children were not substantially contributing to household transmission of SARS-CoV-2. School-based studies indicated that transmission rates in this setting were low. Large-scale studies of transmission chains using data collected from contact tracing and serological studies detecting past evidence of infection would be needed to verify our findings.

A cost-effectiveness and budget impact analysis of C-reactive protein point-of-care testing to guide antibiotic prescribing for acute respiratory tract infections in primary care settings in Ireland: a decision-analytic model.

BACKGROUND: Approximately 60% of antibiotics issued in primary care are for acute respiratory tract infections (RTIs), which are largely self-limiting and do not require antibiotics. Point-of-care testing (POCT) devices that measure C-reactive protein (CRP)-a biomarker for infection-can be used to guide prescribing decisions. OBJECTIVE: We evaluated the cost-effectiveness and budget impact of a national CRP POCT program to guide antibiotic prescribing for acute RTIs in primary care in Ireland. METHODS: We compared CRP POCT with and without enhanced communication skills training of general practitioners against usual care. A probabilistic decision tree was used to investigate cost-effectiveness from the perspective of the healthcare system. The model considered outcomes for the Irish population over a 5-year time horizon. Inputs were synthesized from published studies. Cost-effectiveness was estimated using an incremental cost per prescription avoided. RESULTS: CRP POCT with and without communication training were more costly but more effective than usual care over 5 years. CRP POCT alone was dominated, while the combined intervention had a cost per prescription avoided of €111 (95% CI: €45-243) versus usual care. The budget impact was costly over 5 years, but potential budget savings were available depending on the implementation scenario. The findings were largely robust to sensitivity analyses. CONCLUSIONS: CRP POCT reduces antibiotic prescribing, but increases healthcare costs. The most cost-effective program of CRP POCT includes enhanced communication skills training. Further research on the impact of CRP POCT beyond 5 years is warranted, as well as the potential impact on antimicrobial resistance.

The effectiveness of non-contact thermal screening as a means of identifying cases of Covid-19: a rapid review of the evidence.

The aim of this rapid review is to summarise the evidence on non-contact thermal screening as a method through which to identify cases and reduce the spread of coronavirus disease (Covid-19). The rapid review was conducted in accordance with Cochrane guidelines, with a systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints undertaken from 1 January 2000 up to 7 October 2020. Eleven studies were included. One observational study and two mathematical modelling studies were conducted in the context of the Covid-19 pandemic; the remaining studies were conducted during the influenza A pandemic (H1N1) 2009 (n = 7) or middle east respiratory syndrome (n = 1) pandemics. One systematic review and three rapid reviews were identified and screened for relevant studies. Evidence on the effectiveness of thermal screening contained within this review was limited to points of entry (i.e., airports); thus the applicability to other community settings is uncertain. Thermal screening, implemented as part of a composite of screening measures (self-report of relevant symptoms, contact/travel history), was ineffective in identifying infectious individuals and limiting the spread of disease. Based on limited, low certainty evidence, non-contact thermal screening is ineffective in limiting the spread of Covid-19.

Immune response following infection with SARS-CoV-2 and other coronaviruses: A rapid review.

In this review, we systematically searched and summarized the evidence on the immune response and reinfection rate following SARS-CoV-2 infection. We also retrieved studies on SARS-CoV and MERS-CoV to assess the long-term duration of antibody responses. A protocol based on Cochrane rapid review methodology was adhered to and databases were searched from 1/1/2000 until 26/5/2020. Of 4744 citations retrieved, 102 studies met our inclusion criteria. Seventy-four studies were retrieved on SARS-CoV-2. While the rate and timing of IgM and IgG seroconversion were inconsistent across studies, most seroconverted for IgG within 2 weeks and 100% (N = 62) within 4 weeks. IgG was still detected at the end of follow-up (49-65 days) in all patients (N = 24). Neutralizing antibodies were detected in 92%-100% of patients (up to 53 days). It is not clear if reinfection with SARS-CoV-2 is possible, with studies more suggestive of intermittent detection of residual RNA. Twenty-five studies were retrieved on SARS-CoV. In general, SARS-CoV-specific IgG was maintained for 1-2 years post-infection and declined thereafter, although one study detected IgG up to 12 years post-infection. Neutralizing antibodies were detected up to 17 years in another study. Three studies on MERS-CoV reported that IgG may be detected up to 2 years. In conclusion, limited early data suggest that most patients seroconvert for SARS-CoV-2-specific IgG within 2 weeks. While the long-term duration of antibody responses is unknown, evidence from SARS-CoV studies suggest SARS-CoV-specific IgG is sustained for 1-2 years and declines thereafter.

Alternative clinical specimens for the detection of SARS-CoV-2: A rapid review.

The collection of nasopharyngeal swabs to test for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an invasive technique with implications for patients and clinicians. Alternative clinical specimens from the upper respiratory tract may offer benefits in terms of collection, comfort and infection risk. The objective of this review was to synthesise the evidence for detection of SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) tested saliva or nasal specimens compared with RT-PCR tested nasopharyngeal specimens. Searches were conducted in PubMed, Embase, Europe PMC and NHS evidence from December 2019 to 20 July 2020. Eighteen studies were identified; 12 for saliva, four for nasal and two included both specimen types. For saliva-based studies, the proportion of saliva samples testing positive relative to all positive samples in each study ranged from 82.9% to 100%; detection in nasopharyngeal specimens ranged from 76.7% to 100%; positive agreement between specimens for overall detection ranged from 65.4% to 100%. For nasal-based studies, the proportion of nasal swabs testing positive relative to all positive samples in each study ranged from 81.9% to 100%; detection in nasopharyngeal specimens ranged from 70% to 100%; positive agreement between specimens for overall detection ranged from 62.3% to 100%. The results indicate an inconsistency in the detection of SARS-CoV-2 RNA in the specimen types included, often with neither the index nor the reference of interest detecting all known cases. Depending on the test environment, these clinical specimens may offer a viable alternative to standard. However, at present the evidence is limited, of variable quality, and relatively inconsistent.

SARS-CoV-2 detection, viral load and infectivity over the course of an infection.

OBJECTIVES: To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity. METHODS: A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020. RESULTS: We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance. No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus. CONCLUSION: There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.

One institution's experience in transforming the health sciences library of the future.

Recognizing a need to be more relevant to its constituents, and aligned with institutional priorities, the Taubman Health Sciences Library redefined its mission, roles, and space. This transformation facilitated innovative, team-based collaborations within the health sciences community and the addition of new roles and responsibilities in academic and clinical engagement, research and informatics, enabling technologies, community outreach, and global health. Library space is being redesigned, and a branch library dedicated to interdisciplinary partnerships has been established. Information gained from this experience will be useful to other libraries faced with budget, resource, and staffing challenges and will offer practical ideas for becoming more integrated into the academic, research, and clinical work of the health sciences enterprise.

Simultaneous DNA amplification and detection using a pH-sensing semiconductor system.

We developed an integrated chip for real-time amplification and detection of nucleic acid using pH-sensing complementary metal-oxide semiconductor (CMOS) technology. Here we show an amplification-coupled detection method for directly measuring released hydrogen ions during nucleotide incorporation rather than relying on indirect measurements such as fluorescent dyes. This is a label-free, non-optical, real-time method for detecting and quantifying target sequences by monitoring pH signatures of native amplification chemistries. The chip has ion-sensitive field effect transistor (ISFET) sensors, temperature sensors, resistive heating, signal processing and control circuitry all integrated to create a full system-on-chip platform. We evaluated the platform using two amplification strategies: PCR and isothermal amplification. Using this platform, we genotyped and discriminated unique single-nucleotide polymorphism (SNP) variants of the cytochrome P450 family from crude human saliva. We anticipate this semiconductor technology will enable the creation of devices for cost-effective, portable and scalable real-time nucleic acid analysis.

Real-time PCR detection of the mg219 gene of unknown function of Mycoplasma genitalium in men with and without non-gonococcal urethritis and their female partners in England.

Real-time PCR was employed to detect a region of the Mycoplasma genitalium mg219 gene, a gene of unknown function, in clinical samples. Amplification of DNA and signal production from 15 other species of human mycoplasmas and 14 other bacteria and viruses did not occur. Using a panel of 208 genital and rectal samples, the sensitivity when compared to the modified mgpa gene (encoding the major surface protein MgPa) real-time PCR assay was found to be 100% and the specificity of the assay 99.5% with a positive predictive value of 80% and a negative predictive value of 100%. The mg219 gene was found to be in all strains of M. genitalium and was highly conserved. M. genitalium was detected in 3.9% (11/280, 95% CI 2.1-6.9) of all male specimens, in 7.7% (10/130, 95% CI 4.1-13.7) of patients with non-gonococcal urethritis (NGU) and in 0.7% (1/150, 95% CI <0.01-4.1) of patients without urethritis. The presence of M. genitalium was significantly associated with NGU (P < or =0.01; 95% Cl 0.88-0.98) and non-chlamydial-non-gonococcal urethritis (P=0.0005; 95% Cl 0.84-0.97).

Mechanisms of Cx43 and Cx26 transport to the plasma membrane and gap junction regeneration.

Previous reports have suggested that Cx26 exhibits unique intracellular transport pathways en route to the cell surface compared with other members of the connexin family. To directly examine and compare nascent and steady-state delivery of Cx43 and Cx26 to the plasma membrane and gap junction biogenesis we expressed fluorescent-protein-tagged Cx43 and Cx26 in BICR-M1Rk and NRK cells. Static and time-lapse imaging revealed that both connexins were routed through the Golgi apparatus prior to being transported to the cell surface, a process inhibited in the presence of brefeldin A (BFA) or the expression of a dominant-negative form of Sar1 GTPase. During recovery from BFA, time-lapse imaging of nascent connexin Golgi-to-plasma membrane delivery revealed many dynamic post-Golgi carriers (PGCs) originating from the distal side of the Golgi apparatus consisting of heterogeneous vesicles and long, tubular-like extensions. Vesicles and tubular extensions were also observed in HBL-100 cells expressing a human, disease-linked, Golgi-localized Cx26 mutant, D66H-GFP. A diffuse cell surface rim of fluorescent-protein-tagged wild-type connexins was observed prior to the appearance of punctate gap junctions, which suggests that random fusion of PGCs occurred with the plasma membrane followed by lateral diffusion of connexins into clusters. Fluorescence recovery after photobleaching studies revealed that Cx26-YFP was more mobile within gap junction plaques compared with Cx43-GFP. Intriguingly, Cx43-GFP delivery and gap junction regeneration was inhibited by BFA and nocodazole, whereas Cx26-GFP delivery was prevented by BFA but not nocodazole. Collectively, these studies suggest that during gap junction biogenesis two phylogenetically distinct members of the connexin family, Cx43 and Cx26, share common secretory pathways, types of transport intermediates and turnover dynamics but differ in their microtubule-dependence and mobility within the plasma membrane, which might reflect differences in binding to protein scaffolds.