Development of decellularized conjunctiva as a substrate for the ex vivo expansion of conjunctival epithelium

This study was performed to develop a method to decellularize human conjunctiva and to characterize the tissue in terms of its deoxyribose nucleic acid (DNA) content, tensile strength, collagen denaturation, basement membrane, extracellular matrix components and its potential to support conjunctival epithelial growth. Human conjunctival tissues were subjected to a decellularization process involving hypotonic detergent and nuclease buffers. Variations in sodium dodecyl sulfate concentration (0.05–0.5%, w/v) were tested to determine the appropriate concentration of detergent buffer. DNA quantification, collagen denaturation, cytotoxicity and tensile strength were investigated. Human conjunctival cell growth by explant culture on the decellularized tissue substrate was assessed after 28 days in culture. Samples were fixed and paraffin embedded for immunohistochemistry including conjunctival epithelial cell markers and extracellular matrix proteins. Conjunctival tissue from 20 eyes of 10 donors (age range 65–92 years) was used. Decellularization of human conjunctiva was achieved to 99% or greater DNA removal (p < 0.001) with absence of nuclear staining. This was reproducible at the lowest concentration of sodium dodecyl sulfate (0.05% w/v). No collagen denaturation (p = 0.74) and no difference in tensile strength parameters was demonstrated following decellularization. No significant difference was noted in the immunolocalization of collagen IV, laminin and fibronectin, or in the appearance of periodic acid–Schiff‐stained basement membranes following decellularization. The decellularized tissue did not exhibit any cytotoxicity and explant culture resulted in the growth of stratified conjunctival epithelium. Allogeneic decellularized human conjunctiva can be successfully decellularized using the described protocol. It represents a novel substrate to support the expansion of conjunctival epithelium for ocular surface cellular replacement therapies. Copyright © 2017 John Wiley & Sons, Ltd.     

How do people interpret information about colorectal cancer screening: observations from a think‐aloud study

Background

The English NHS Bowel Cancer Screening Programme biennially invites individuals aged 60–74 to participate in screening. The booklet, ‘Bowel Cancer Screening: The Facts'' accompanies this invitation. Its primary aim is to inform potential participants about the aims, advantages and disadvantages of colorectal cancer screening.

Objective

To provide detailed commentary on how individuals process the information contained within ‘The Facts’ booklet.

Design, setting and participants

This study comprised of 18 interviews with individuals aged 45–60 and used a ‘think‐aloud’ paradigm in which participants read aloud the booklet. Participant utterances (verbal statements made in response to researcher‐led prompts) were transcribed and analysed using a combination of content and thematic analysis.

Results

A total of 776 coded utterances were analysed (mean = 43.1 per person; range = 8–95). While overall comprehension was satisfactory, several problem areas were identified such as the use of complex unfamiliar terminology and the presentation of numerical information. Specific sections such as colonoscopy risk information evoked negative emotional responses. Participants made several suggestions for ways in which comprehension might be improved.

Conclusion

Public perceptions of the NHS Bowel Cancer Screening Programme information materials indicated that specific aspects of the booklet were difficult to process. These materials may be an appropriate target to improve public understanding of the aims, benefits and disadvantages of colorectal cancer screening. These findings will contribute to a broader NIHR‐funded project that aims to design a supplementary ‘gist‐based’ information leaflet suitable for low literacy populations.     

Can morbidity and mortality of SLE be improved?

Systemic lupus erythematosus (SLE) is the second most common autoimmune disorder (after thyroid disease) in women of childbearing age. Lupus is increasingly being recognized throughout the world's population. The incidence and prevalence of SLE varies among racial and ethnic groups. Lupus patient survival has significantly improved over the past five decades, but a three- to fivefold increased risk of death remains compared with the general population. As lupus patients survive longer, these individuals face a range of complications from the disease itself or consequent to its treatment. Emerging data from epidemiological studies underscore the importance of incorporating race and ethnicity in understanding the risk factors leading to the significant burden of mortality and morbidity associated with this disease. This chapter describes the epidemiology of lupus with a focus on racial and ethnic differences, reviews the mortality associated with the disease, discusses selected complications associated with morbidity related to the disease and highlights areas where we can improve mortality and morbidity.     

Lhermitte's sign as a complication of cisplatin-containing chemotherapy for testicular cancer

Lhermitte's sign is reported in 14 patients receiving chemotherapy for metastatic testicular cancer. In six patients the typical symptoms appeared during chemotherapy: in five patients within 1 month of treatment and in one patient at 2 months. The duration of symptoms ranged from 2 to approximately 8 months. No patient had received radiotherapy to the cervical or dorsal spinal cord. The complication is ascribed to cisplatin, the only drug common to all 14 patients.     

Noninvasive Streptococcus pneumoniae Serotypes Recovered from Hospitalized Adult Patients in the United States in 2009 to 2012

This study was conducted to determine the serotype distribution and trends over time of Streptococcus pneumoniae strains associated with noninvasive infections among adult patients ≥18 years of age in the United States (2009 to 2012). A total of 2,927 S. pneumoniae isolates recovered from patients presenting with respiratory infections and obtained mainly (87.0%) from lower respiratory tract specimens (sputum) were included. The levels of the 7-valent pneumococcal conjugate vaccine (PCV7) serotypes remained stable over the 4-year study period (4.6% to 5.5%; P = 0.953). Overall, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were identified in 32.7% of samples, declining from 33.7% to 35.5% in 2009 to 2011 to 28.2% in 2012 (P = 0.007), with a significant decrease in the levels of serotypes 7F (P = 0.013) and 6A (P = 0.010). The levels of 19A remained constant (15.8% to 17.1%) during 2009 to 2011, dropping to 12.2% in 2012 (P = 0.089). The prevalence of serotypes associated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), but not PCV13, remained generally stable; however, the prevalence of serotypes 15B and 15C (15B/15C) increased from 2.7% to 6.3% (P = 0.010). The proportion of nonvaccine serotypes increased gradually during the study period (P = 0.044), particularly for serotype 35B (from 3.6% in 2009 to 8.2% in 2012; P = 0.001). Nonsusceptibility rates for penicillin (susceptible breakpoint, ≤2 μg/ml) and clindamycin against PCV7 serotypes decreased over the period. These results suggest the emergence of indirect effects following introduction of PCV13 for infants and young children; continued surveillance is needed to assess the burden of PCV13 serotypes in the adult population after the implementation of age-based recommendations in the United States.     

Why do patients with cancer access out-of-hours primary care? A retrospective study

Background

Identifying why patients with cancer seek out-of-hours (OOH) primary medical care could highlight potential gaps in anticipatory cancer care.

Aim

To explore the reasons for contact and the range and prevalence of presenting symptoms in patients with established cancer who presented to a primary care OOH department.

Design and setting

A retrospective review of 950 anonymous case records for patients with cancer who contacted the OOH general practice service in Grampian, Scotland between 1 January 2010 and 31 December 2011.

Method

Subjects were identified by filtering the OOH computer database using the Read Codes ‘neoplasm’, ‘terminal care’, and ‘terminal illness’. Consultations by patients without cancer and repeated consultations by the same patient were excluded. Data were anonymised. Case records were read independently by two authors who determined the presenting symptom(s).

Results

Anonymous case records were reviewed for 950 individuals. Eight hundred and fifty-two patients made contact because of a symptom. The remaining 97 were mostly administrative and data were missing for one patient. The most frequent symptoms were pain (n = 262/852, 30.8%); nausea/vomiting (n = 102/852, 12.0%); agitation (n = 53/852, 6.2%); breathlessness (n = 51/852, 6.0%); and fatigue (n = 48/852, 5.6%). Of the 262 patients who presented with pain, at least 127 (48.5%) had metastatic disease and 141 (53.8%) were already prescribed strong opiate medication.

Conclusion

Almost one-third of patients with cancer seeking OOH primary medical care did so because of poorly controlled pain. Pain management should specifically be addressed during routine anticipatory care planning.