Sequence specificity defines the effectiveness of PPMOs targeting Pseudomonas aeruginosa.

Development of new therapeutics against antibiotic resistant pathogenic bacteria is recognized as a priority across the globe. We have reported using peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) as species-specific antibiotics. The oligo sequences, 11 bases are designed to be complementary to specific essential genes near the Shine-Dalgarno site and inhibit translation. Here, we analyzed target specificity and the impact of genetic mutations on lead PPMOs targeting the rpsJ or acpP gene of Pseudomonas aeruginosa. Mutants in P. aeruginosa PAO1 were generated with four, two, or one base-pair mutations within the 11-base target sequence of the rpsJ gene. All mutants exhibited increased MICs compared to wild-type PAO1 when treated with the RpsJ PPMO, and the increase in the MICs was proportional to the number of base-pair mutations. Among single base-pair mutants, mutations in the middle of the sequence were more impactful than mutations in 5' or 3' end of the sequence. The increased MICs shown by the rpsJ mutants could be reversed by PPMOs designed to target the mutated rpsJ sequence. BALB/c mice infected intratracheally with mutants demonstrated increased lung burden when treated with RpsJ PPMO compared to wild-type PAO1-infected mice treated with RpsJ PPMO. Treating mice with a PPMOs designed to specifically target the mutant sequence was more effective against these mutant strains. These experiments confirm target specificity of two lead P. aeruginosa PPMOs and illustrate one potential mechanism of resistance that could emerge from an antisense approach.

Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations.

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making.

Hormonal correlates of male dominance rank, age, and genital colouration in vervet monkey (Chlorocebus pygerythrus).

Primates are the most colourful members of the Mammalian clade. In vervet monkeys (Chlorocebus pygerythrus), males are characterized by their red penis and blue scrotum. Such colour signals are often used in conspecific communication, and thus could be used to convey signaller condition. We quantified scrotal and penile colour characteristics using digital photographs between May-June 2016 from males in two neighboring groups along the shores of Lake Nabugabo, Uganda. We examined the relationship between fecal hormones, male dominance rank, age (adult vs. immature), and colour. Adult males were higher ranking than immatures, but there were no rank or age differences in fecal hormone levels. Glucocorticoids and androgens were positively correlated in immature, but not adult males. All scrotal characteristics were predicted by age, with adult males having more teal (i.e., less blue, more green) and more luminant scrota. Within adult males, those with higher androgens levels had more saturated blue scrotal colouration and higher-ranking males were more luminant. Penile colouration was also associated with age and rank. High-ranking males had a more saturated red penis, and adult male penile colour was more luminant and bluer than in immature males. Our findings are consistent with previous reports that scrotal colouration advertises sexual or reproductive maturity (i.e., age), but we also find that within adult males, colour also advertises dominance rank and may be mediated by androgen levels. Penile colouration also appears to signal information about male age and dominance rank but does not appear to be mediated by hormones.

The role of the genetic testing industry in patient education of hereditary cancer: An observational study assessing the quality of patient education videos.

OBJECTIVES: Genetic testing (GT) companies have developed patient education videos to supplement or replace pre-test genetic counseling (GC) by certified genetic counselors (CGC). The aim of this study was to assess the quality of these videos compared to the standard of care (SOC). METHODS: Videos from four major GT companies were selected from an internet search identifying pre-test patient education videos. A scoring rubric with 22 questions and 36 total points was devised to assess quality metrics, as described by the National Cancer Institute and National Society of Genetic Counselors. Twenty-two individuals with varying genetics expertise (3 gynecologic oncologists, 3 academic generalists, 4 CGC, a genetics community health worker, 3 cancer care navigators, and 8 medical students) scored each video. Scorers were blinded to others' assessments. RESULTS: Invitae had the highest median score (26/36), followed by Myriad (22/36), Ambry (17.5/36), and Color (15/36). All videos scored highly in explaining DNA basics, cancer development, and hereditary cancer predisposition. All addressed benefits of GT but failed to address potential disadvantages. All scored poorly in explaining medical terms and different GT options. There was variability in addressing patient concerns including cost, privacy, and procedure. CONCLUSIONS: There is significant variation in the content of pre-test patient education videos between GT companies. None of the videos met the SOC for pre-test GC, and none addressed disadvantages of GT, possibly due to a conflict of interest. With improvement in content, accessibility, and use of interactive platforms, these videos may serve as an adjunct to in-person pre-test GC.

Evolutionarily distinct amphibians are disproportionately lost from human-modified ecosystems.

Humans continue to alter terrestrial ecosystems, but our understanding of how biodiversity responds is still limited. Anthropogenic habitat conversion has been associated with the loss of evolutionarily distinct bird species at local scales, but whether this evolutionary pattern holds across other clades is unknown. We collate a global dataset on amphibian assemblages in intact forests and nearby human-modified sites to assess whether evolutionary history influences susceptibility to land conversion. We found that evolutionarily distinct amphibian species are disproportionately lost when forested habitats are converted to alternative land-uses. We tested the hypothesis that grassland-associated amphibian lineages have both higher diversification and are pre-adapted to human landscapes, but found only weak evidence supporting this. The loss of evolutionarily distinct amphibians with land conversion suggests that preserving remnant forests will be vital if we aim to preserve the amphibian tree of life in the face of mounting anthropogenic pressures.

Merkel Cell Carcinoma: rising incidence in the East of England.

BACKGROUND: Merkel Cell Carcinoma (MCC) is an infrequent but highly aggressive skin cancer. Five-year survival rates are poor, as there are high rates of metastases at primary diagnoses. Recurrences are also common. There is controversy about actual incidence rates which vary considerably between developed countries with majority populations of fair skin types. OBJECTIVES: We report the age-standardized incidence rates of MCC for both males and females from the East of England, and use linear regression analyses to estimate numbers of cases for 2020 and 2025 to aid healthcare planning and allocation of resources. METHODS: All cases of MCC diagnosed histopathologically between 1st January 2004 and 31st December 2013 were extracted from the databases of the Eastern Office, National Cancer Registration Service, Public Health England, and the Pathology department of the Norfolk and Norwich University Hospital, which serves as the tertiary referral centre for the region. Age-standardization incidence rate calculations (ASIs) and linear regression analyses were performed. RESULTS: The ASIs for males and females were 0.70 and 1.08 per 100 000 person-years respectively. The total age-adjusted incidence rate was therefore 1.78 per 100 000 person-years. The ratio of female: male disease was 3:2. The total number of cases for this region over the time period studied was 73. There has been a threefold increase over this period. Estimated cases for this region are 17 in 2020, and 22 in 2025. Estimated UK cases for 2020 are 920, and 1134 in 2025. CONCLUSIONS: MCC is increasing steadily in the East of England, and has risen threefold over the last 10 years and is similar to the highest reported rates from Western Australia. These data are 12-fold higher than previous UK estimates, and suggest that the incidence rate is also rising in other regions of the UK.

Stage at diagnosis and early mortality from cancer in England.

BACKGROUND: Stage at diagnosis is a key predictor of overall cancer outcome. For the first time, stage completeness is high enough for robust analysis for the whole of England. METHODS: We analysed data from the National Cancer Registration Service's (NCRS) Cancer Analysis System on persons diagnosed with breast, colorectal, lung, prostate or ovarian cancers in England in 2012. One-year relative survival (followed-up to the end of 2013) was calculated along with adjusted excess rate ratios, for mortality within 1 year. RESULTS: One-year relative survival decreased with increasing stage at diagnosis. For breast, prostate and colorectal cancers survival showed a major reduction for stage 4 cancers, whereas for lung and ovarian cancers there were substantial decreases in relative survival for each level of increase in stage. Excess rate ratios for mortality within 1 year of diagnosis showed that stage and age were the most important cofactors, but they also identified the statistically significant effects of sex, income deprivation and geographic area of residence. CONCLUSIONS: Further reductions in mortality may be most effectively achieved by diagnosing all cancers before they progress to stage 4, but for lung and ovarian cancers there is also a need for a stage shift to earlier stages together with efforts to improve stage-specific survival at all stages.

The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women.

BACKGROUND: Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain. METHODS: We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights. RESULTS: For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population). CONCLUSIONS: The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.

Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma.

BACKGROUND: Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis. METHODS: We used data on patients diagnosed with malignant melanoma in the East of England (2006-2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model. RESULTS: Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III-IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population. CONCLUSIONS: Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score. METHODS: Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort. RESULTS: In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information. CONCLUSIONS: The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.

Sustained Alzheimer's amyloid pathology in myeloid differentiation protein-88-deficient APPswe/PS1 mice.

BACKGROUND: Most Alzheimer's disease (AD) cases arise sporadically and may involve innate immune activation of microglial expressed Toll-like receptors regulated through the myeloid differentiation protein 88 (MyD88) pathway. OBJECTIVE: It was the aim of this study to test the innate immune involvement in AD pathology. METHODS: We mated APPsw/PS1ΔE9 mice with MyD88-deficient mice. RESULTS: Progeny mice had similar levels of soluble amyloid-ß peptides, amyloid plaque density and neuroimmune staining patterns. However, double-transgenic mice did show a significantly reduced life expectancy. CONCLUSION: Our findings indicate that impaired innate immune responses may play a role in AD pathology.

How much of the deprivation gap in cancer survival can be explained by variation in stage at diagnosis: an example from breast cancer in the East of England.

Socioeconomic differences in cancer patient survival exist in many countries and across cancer sites. In our article, we estimated the number of deaths in women with breast cancer that could be avoided within 5 years from diagnosis if it were possible to eliminate socioeconomic differences in stage at diagnosis. We analysed data on East of England women with breast cancer (2006-2010). We estimated survival for different stage-age-deprivation strata using both the observed and a hypothetical stage distribution (assuming all women acquired the stage distribution of the most affluent women). Data were analysed on 20,738 women with complete stage information (92%). Affluent women were less likely to be diagnosed in advanced stage. Relative survival decreased with increasing level of deprivation. Eliminating differences in stage at diagnosis could be expected to nearly eliminate differences in relative survival for women in deprivation groups 3 and 4, but would only approximately halve the difference in relative survival for women in the most deprived group (5). This means, for a typical cohort of women diagnosed in a calendar year with breast cancer, eliminating deprivation differences in stage at diagnosis would prevent ∼40 deaths in the East of England from occurring within 5 years from diagnosis. Using appropriate weighting we estimated the respective number of avoidable deaths for the whole of England to be ∼450. The findings suggest that policies aimed at reducing inequalities in stage at diagnosis between women with breast cancer are important to reduce inequalities in breast cancer survival.

Changing presentation of prostate cancer in a UK population--10 year trends in prostate cancer risk profiles in the East of England.

BACKGROUND: Prostate cancer incidence is rising in the United Kingdom but there is little data on whether the disease profile is changing. To address this, we interrogated a regional cancer registry for temporal changes in presenting disease characteristics. METHODS: Prostate cancers diagnosed from 2000 to 2010 in the Anglian Cancer Network (n=21,044) were analysed. Risk groups (localised disease) were assigned based on NICE criteria. Age standardised incidence rates (IRs) were compared between 2000-2005 and 2006-2010 and plotted for yearly trends. RESULTS: Over the decade, overall IR increased significantly (P<0.00001), whereas metastasis rates fell (P<0.0007). For localised disease, IR across all risk groups also increased but at different rates (P<0.00001). The most striking change was a three-fold increase in intermediate-risk cancers. Increased IR was evident across all PSA and stage ranges but with no upward PSA or stage shift. In contrast, IR of histological diagnosis of low-grade cancers fell over the decade, whereas intermediate and high-grade diagnosis increased significantly (P<0.00001). CONCLUSION: This study suggests evidence of a significant upward migration in intermediate and high-grade histological diagnosis over the decade. This is most likely to be due to a change in histological reporting of diagnostic prostate biopsies. On the basis of this data, increasing proportions of newly diagnosed cancers will be considered eligible for radical treatment, which will have an impact on health resource planning and provision.

Socio-demographic inequalities in stage of cancer diagnosis: evidence from patients with female breast, lung, colon, rectal, prostate, renal, bladder, melanoma, ovarian and endometrial cancer.

BACKGROUND: Understanding socio-demographic inequalities in stage at diagnosis can inform priorities for cancer control. PATIENTS AND METHODS: We analysed data on the stage at diagnosis of East of England patients diagnosed with any of 10 common cancers, 2006-2010. Stage information was available on 88 657 of 98 942 tumours (89.6%). RESULTS: Substantial socio-demographic inequalities in advanced stage at diagnosis (i.e. stage III/IV) existed for seven cancers, but their magnitude and direction varied greatly by cancer: advanced stage at diagnosis was more likely for older patients with melanoma but less likely for older patients with lung cancer [odds ratios for 75-79 versus 65-69 1.60 (1.38-1.86) and 0.83 (0.77-0.89), respectively]. Deprived patients were more likely to be diagnosed in advanced stage for melanoma, prostate, endometrial and (female) breast cancer: odds ratios (most versus least deprived quintile) from 2.24 (1.66-3.03) for melanoma to 1.31 (1.15-1.49) for breast cancer. In England, elimination of socio-demographic inequalities in stage at diagnosis could decrease the number of patients with cancer diagnosed in advanced stage by ∼5600 annually. CONCLUSIONS: There are substantial socio-demographic inequalities in stage at diagnosis for most cancers. Earlier detection interventions and policies can be targeted on patients at higher risk of advanced stage diagnosis.

Influence of age, social patterns and nasopharyngeal carriage on antibodies to three conserved pneumococcal surface proteins (PhtD, PcpA and PrtA) in healthy young children.

The acquisition of specific antibodies is paramount to protect children against pneumococcal diseases, and a better understanding of how age, ethnicity and/or Streptococcus pneumoniae (Spn) nasopharyngeal carriage influence the acquisition of antibodies to pneumococcal surface proteins (PSP) is important for the development of novel serodiagnostic and immunisation strategies. IgG antibody titres against three conserved PSP (PhtD, PcpA and PrtA) in the sera of 451 healthy children aged 1 to 24 months from Israel [Jewish (50.1 %) and Bedouin (49.9 %)] were measured by enzyme-linked immunosorbent assay (ELISA), while nasopharyngeal swabs from these children were assessed for the presence of Spn. Globally, anti-PhtD and anti-PrtA geometric mean concentrations (GMC; EU/ml) were high at <2.5 months of age [PhtD: 35.3, 95 % confidence interval (CI) 30.6-40.6; PrtA: 71.2, 95 % CI 60-84.5], was lower at 5-7 months of age (PhtD: 10, 95 % CI 8-12.4; PrtA: 17.9, 95 % CI 14.4-22.1) and only increased after 11 months of age. In contrast, an increase in anti-PcpA was observed at 5-7 months of age. Anti-PcpA and anti-PrtA, but not anti-PhtD, were significantly higher in Bedouin children (PcpA: 361.6 vs. 226.3, p = 0.02; PrtA: 67.2 vs. 29.5, p < 0.001) in whom Spn nasopharyngeal carriage was identified earlier (60 % vs. 38 % of carriers <6 months of age, p = 0.002). Spn carriage was associated with significantly higher anti-PSP concentrations in carriers than in non-carriers (p < 0.001 for each PSP). Thus, age, ethnicity and, essentially, nasopharyngeal carriage exert distinct cumulative influences on infant responses to PSP. These specific characteristics are worthwhile to include in the evaluation of pneumococcal seroresponses and the development of new PSP-based vaccines.

Dynamics of childhood invasive meningococcal disease in Israel during a 22-year period (1989-2010).

AIM: To describe the dynamics in the incidence of childhood invasive meningococcal disease (IMD) in Israel during a 22-year period (1989-2010). METHODS: A longitudinal prospective surveillance in all 27 medical centers with pediatric services in Israel. All cases of children <15 years old with positive blood/cerebrospinal fluid (CSF) culture for Neisseria meningitidis were reported. Demographic, clinical, and bacteriological data were recorded. Meningococcal vaccine was not routinely given to Israeli children during the study period. RESULTS: The mean age ± standard deviation (SD) among the 743 cases was 40.7 ± 40.2 months. The mean yearly incidence/100,000 was 2.0 ± 0.8. Age-specific incidences were 8.7 ± 2.8, 2.9 ± 1.5, and 0.8 ± 0.5 for children <1, 1-4, and >4 years old, respectively. The overall incidence decreased significantly from 3.7 in 1989 to 1.5 in 2010. Meningitis constituted 69.2 % of all cases. The most common serogroups were: B (76.9 %), C (10.9 %), Y (8.0 %), and W(135) (2.9 %). 78.6 % of all serogroup B isolates were from children <5 years old (p < 0.01). Serogroup C was found mainly in children ≥5 years old (63.4 %). The case fatality rates (CFRs) for children <1, 1-4, >4 years old, and the total study population were 9.2, 12.3, 7.7, and 9.9 %, respectively. CFRs were higher for children without meningitis (14.9 %) compared to children with meningitis (7.9 %) (p < 0.01). CONCLUSIONS: Overall, and for serogroups B and W135, childhood IMD rates decreased significantly in Israel during the study period, without routine vaccine usage. The most common serogroup in all age groups was B, which was most prevalent in children <5 years old. No change in the trend of the overall CFR was noted during the study period.

Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.

Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance.The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in 5 years.

Variation in colorectal cancer treatment and survival: a cohort study covering the East Anglia region.

AIM: National guidelines for colorectal cancer management aim to optimize cancer outcomes irrespective of postcode. However, in order to ensure equal performance of cancer services, variation in outcome must be monitored and intelligently assessed. In this study, detailed regional cancer registry data were used to quantify and explore the reasons for variation in colorectal cancer outcomes at nine hospitals in East Anglia. METHOD: We analysed data on colorectal cancers registered by the Eastern Cancer Registry and Information Centre (ECRIC) between 1999 and 2005. Tumours were grouped by site, in keeping with surgical resection. Multivariable Cox regression models were used to identify the effects of patient, disease and treatment variables on an individual's risk of death. RESULTS: After adjusting for demographic, disease and treatment variables there were significant differences in survival among hospitals in emergency admissions with cancer of the right colon, in elective admissions with cancer of the left, sigmoid or recto-sigmoid colon and in emergency admissions with cancer of the rectum. There were also differences among hospitals in terms of perioperative death, nonsurgical management and numbers of nodes examined. For rectal cancers, rates of anterior resection compared with abdominoperineal excision differed, as well as the use of neoadjuvant radiotherapy. CONCLUSION: Detailed analysis of demographic, disease and treatment factors are required when comparing the survival of individuals with colorectal cancer across hospitals. The results imply that cancer management was not consistent across East Anglia in 1999-2005 but the reasons for this are uncertain. Nevertheless, 5-year age-standardized survival with colon cancer in the Anglia Cancer Network region is currently among the best in the UK.

Basal cell carcinoma epidemiology in the UK: the elephant in the room.

BACKGROUND: UK Cancer registries have difficulties in recording the incidence of basal cell carcinoma (BCC). AIM: To estimate the total numbers of BCCs in the UK requiring surgical treatment. METHODS: The histopathology records of each year from 1999 to 2010 were examined to estimate the total annual numbers of BCCs and of people with BCC in the East Norfolk and Waveney area of the UK. RESULTS: Over this period, the numbers of patients with surgically treated BCCs increased by 81%, and the numbers of BCCs by 70%. The ratio of BCCs recorded by the cancer registry was 2-2.2 times lower than that recorded in the histopathology data. Extrapolating the data to the UK population suggests that in 2010, approximately 200,000 patients had 247,000 BCCs treated surgically (this estimate does not include those treated by other means such as cryotherapy, topical chemotherapy, photodynamic therapy or radiotherapy, without histology). In 2008, 114,000 nonmelanoma skin cancers were registered in England and Wales and 309,000 total cancers (excluding nonmelanoma skin cancers) were registered in the UK. CONCLUSIONS: These data indicate that in the UK, BCC is nearly as common as all other cancers in all other body sites combined.

Exogenous Dp71 restores the levels of dystrophin associated proteins but does not alleviate muscle damage in mdx mice.

Dp71 is a non-muscle product of the Duchenne muscular dystrophy gene. It consists of the cysteine-rich and C-terminal domains of dystrophin. We have generated transgenic mdx mice which do not have dystrophin but express Dp71 in their muscle. In these mice, Dp71 was localized to the plasma membrane and restored normal levels of dystrophin associated proteins (DAPs), indicating that Dp71 is capable of interacting with the DAPs in a similar manner to dystrophin. However, the presence of Dp71 and DAPs in the muscle fibres of mdx mice was not sufficient to alleviate symptoms of muscle degeneration.