Exploring patient experiences with a telehealth approach for the PRO-ACTIVE trial intervention in head and neck cancer patients.

INTRODUCTION: Following the COVID-19 directive to cease non-essential services, a rapid shift was made in the delivery of Speech Language Pathology (SLP) dysphagia management in the 3-arm, randomized PRO-ACTIVE trial. To inform future programs, this study explored patients' experiences with telehealth when the planned in-person SLP intervention was moved to a telehealth modality. METHODS: A theory-guided qualitative descriptive approach was used. Willing participants who had received at least one telehealth swallowing therapy session participated in a one-time semi-structured interview. Interview transcripts were subjected to a standard qualitative content/theme analysis. Researchers reviewed all transcripts and used a multi-step analysis process to build a coding framework through consensus discussion. Summaries and key messages were generated for each code. RESULTS: Eleven participants recounted their telehealth experiences and reported feeling satisfied, comfortable and confident with the session(s). They identified that previous experience with teleconferencing, access to optimal technical equipment, clinician skill, and caregiver assistance facilitated their telehealth participation. Participants highlighted that telehealth was beneficial as it reduced commuting time, COVID-19 exposure and fatigue from travel; and also allowed caregiver participation particularly during COVID. In comparing their in-person SLP sessions to telehealth sessions, limitations were also identified, including: lack of previous experience with and/or poor access to technology, and less opportunity for personalization. Participants indicated that use of phone alone was less preferred than an audio/video platform. DISCUSSION: Patients reported that overall, telehealth sessions did not compromise their learning experience when compared to in-person sessions. Patients benefited from use of telehealth in several ways despite some limitations of the use of technology. Patient feedback about telehealth provides an important perspective that may be critical to inform best practices for care delivery.

The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews.

BACKGROUND: Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. METHODS: PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. RESULTS: Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. CONCLUSIONS: This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

The PRO-ACTIVE trial protocol: a randomized study comparing the effectiveness of PROphylACTic swallow InterVEntion for patients receiving radiotherapy for head and neck cancer.

BACKGROUND: Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. METHODS: This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. DISCUSSION: Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. TRIAL REGISTRATION: The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov , under the identifier NCT03455608 ; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).

Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants.

Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established inflammation in animal models. We conducted a pilot safety and feasibility trial of autologous Treg cell therapy in three kidney transplant recipients with subclinical inflammation noted on 6-month surveillance biopsies. Tregs were purified from peripheral blood and polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received a single infusion of ~320 × 106 (319, 321, and 363.8 × 106 ) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow-up biopsies and urinary biomarkers. Nearly 1 × 109 (0.932, 0.956, 1.565 × 109 ) Tregs were successfully manufactured for each patient. There were no infusion reactions or serious therapy-related adverse events. The infused cells demonstrated patterns of persistence and stability similar to those observed in non-immunosuppressed subjects receiving the same dose of Tregs. Isolation and expansion of Tregs is feasible in kidney transplant patients on immunosuppression. Infusion of these cells was safe and well tolerated. Future trials will test the efficacy of polyclonal and donor alloantigen-reactive Tregs for the treatment of inflammation in kidney transplants.

Challenges and insights in implementing coordinated care between oncology and primary care providers: a Canadian perspective.

We report here on the current state of cancer care coordination in Canada and discuss challenges and insights with respect to the implementation of collaborative models of care. We also make recommendations for future research. This work is based on the findings of the Canadian Team to Improve Community-Based Cancer Care Along the Continuum (canimpact) casebook project. The casebook project identified models of collaborative cancer care by systematically documenting and analyzing Canadian initiatives that aim to improve or enhance care coordination between primary care providers and oncology specialists. The casebook profiles 24 initiatives, most of which focus on breast or colorectal cancer and target survivorship or follow-up care. Current key challenges in cancer care coordination are associated with establishing program support, engaging primary care providers in the provision of care, clearly defining provider roles and responsibilities, and establishing effective project or program planning and evaluation. Researchers studying coordinated models of cancer care should focus on designing knowledge translation strategies with updated and refined governance and on establishing appropriate protocols for both implementation and evaluation.

Factors influencing adherence to cancer treatment in older adults with cancer: a systematic review.

BACKGROUND: Cancer is a disease that mostly affects older adults. Treatment adherence is crucial to obtain optimal outcomes such as cure or improvement in quality of life. Older adults have numerous comorbidites as well as cognitive and sensory impairments that may affect adherence. The aim of this systematic review was to examine factors that influence adherence to cancer treatment in older adults with cancer. PATIENTS AND METHODS: Systematic review of the literature published between inception of the databases and February 2013. English, Dutch, French and German-language articles reporting cross-sectional or longitudinal, intervention or observational studies of cancer treatment adherence were included. Data sources included MEDLINE, EMBASE, PsychINFO, Cumulative Index to Nursing and Allied Health (CINAHL), Web of Science, ASSIA, Ageline, Allied and Complementary Medicine (AMED), SocAbstracts and the Cochrane Library. Two reviewers reviewed abstracts and abstracted data using standardized forms. Study quality was assessed using the Mixed Methods Appraisal Tool 2011. RESULTS: Twenty-two manuscripts were identified reporting on 18 unique studies. The quality of most studies was good. Most studies focused on women with breast cancer and adherence to adjuvant hormonal therapy. More than half of the studies used data from administrative or clinical databases or chart reviews. The adherence rate varied from 52% to 100%. Only one qualitative study asked older adults about reasons for non-adherence. Factors associated with non-adherence varied widely across studies. CONCLUSION: Non-adherence was common across studies but little is known about the factors influencing non-adherence. More research is needed to investigate why older adults choose to adhere or not adhere to their treatment regimens taking into account their multimorbidity.

ESMO expert consensus statements on the screening and management of financial toxicity in patients with cancer.

BACKGROUND: Financial toxicity, defined as both the objective financial burden and subjective financial distress from a cancer diagnosis and its treatment, is a topic of interest in the assessment of the quality of life of patients with cancer and their families. Current evidence implicates financial toxicity in psychosocial, economic and other harms, leading to suboptimal cancer outcomes along the entire trajectory of diagnosis, treatment, supportive care, survivorship and palliation. This paper presents the results of a virtual consensus, based on the evidence base to date, on the screening and management of financial toxicity in patients with and beyond cancer organized by the European Society for Medical Oncology (ESMO) in 2022. METHODS: A Delphi panel of 19 experts from 11 countries was convened taking into account multidisciplinarity, diversity in health system contexts and research relevance. The international panel of experts was divided into four working groups (WGs) to address questions relating to distinct thematic areas: patients with cancer at risk of financial toxicity; management of financial toxicity during the initial phase of treatment at the hospital/ambulatory settings; financial toxicity during the continuing phase and at end of life; and financial risk protection for survivors of cancer, and in cancer recurrence. After comprehensively reviewing the literature, statements were developed by the WGs and then presented to the entire panel for further discussion and amendment, and voting. RESULTS AND DISCUSSION: A total of 25 evidence-informed consensus statements were developed, which answer 13 questions on financial toxicity. They cover evidence summaries, practice recommendations/guiding statements and policy recommendations relevant across health systems. These consensus statements aim to provide a more comprehensive understanding of financial toxicity and guide clinicians globally in mitigating its impact, emphasizing the importance of further research, best practices and guidelines.

Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes.

CD4(+) memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4(+) T cell turnover would be greater in type 1 diabetes subjects compared to controls. In vitro studies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide ((2) H(2)O) to assess in vivo turnover of CD4(+) T cell subsets in T1D (n = 10) and control subjects (n = 10). Serial samples of naive, memory and regulatory (T(reg)) CD4(+) T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography-mass spectrometry (GC-MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f, n = 20), turnover rate (k, n = 20), proliferation (p, n = 10) and disappearance (d*, n = 10). Although turnover of T(regs) was greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in T(reg) or naive kinetics. However, turnover of CD4(+) memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating the in vivo kinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4(+) memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.

Anthropometric correlates of lipoprotein profile and blood pressure in high BMI African American children.

OBJECTIVE: To explore the association of anthropometric indices with lipoprotein profile and blood pressure as risk factors of cardiovascular disease, in African American (AA) children. METHODS: A cross-sectional analysis was carried out on children aged 9-13 years with BMI >85th percentile. Height, weight, waist and hip circumferences, % body fat and blood pressure [systolic (sBP) and diastolic (dBP)] were measured. Fasting plasma levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), intermediate density lipoprotein cholesterol (IDL-C) and very low-density lipoprotein cholesterol (VLDL-C) were analysed. RESULTS: After accounting for age, gender and pubertal status of the child, multiple linear regression models showed that waist circumference and BMIz were strong predictors for lipoprotein variables. In independent analysis, waist circumference and BMI z-scores were found to be interdependently associated with TG, LDL-C:HDL-C ratio, VLDL-C and sBPz. However, for HDL-C, TG:HDL-C ratio and dBPz, waist circumference was independently and more strongly associated with these risk factors than BMI. CONCLUSION: Waist circumference was a stronger predictor for lipoprotein variables and blood pressure in high BMI AA children than other anthropometric indices, and may be adequate as a screening test to identify children who are at increased risk for cardiovascular disease.

The utility of publicly reported cancer treatment wait time information for patients and health care providers.

AIMS: To determine the utility of web-based radiation wait time information for patients and health care providers in decision-making. To revise the information using a simulated laboratory environment and to re-evaluate the new web-based information. MATERIALS AND METHODS: An online 'pop-up' survey on the Cancer Care Ontario (CCO) website measured user satisfaction. Qualitative data were gathered through patient focus groups and physician interviews. On the basis of the analysis, the website was revised and usability testing conducted. The information was re-evaluated by end-users through survey methodology. RESULTS: The majority accessing the wait time website were patients and family members. The modal age of use of the website was 31-50 years. Patients found the information more helpful after redesign than health professionals, but both found the language less easy to understand, highlighting the need to continuously evaluate the effectiveness of the website. Patients did not identify themselves as consumers of wait time information. Their expectation was that physicians would determine the urgency for treatment and would ensure timely access to care. Physicians reported that they did not use the CCO website on wait times and would not use the data for decision-making. Referrals were based on urgency of care and usual referral patterns. Referral patterns did not shift to centres with shorter wait times. CONCLUSIONS: The results of this study did not confirm the usefulness of the web-based wait time information for patients and physicians as a resource on how to obtain timely access to radiation treatment. Patients relied on their physician to manage their access to treatment according to the urgency of their clinical condition. Physicians preferred their established referral process rather than referring their patients to centres with shorter wait times. As patients become more computer savvy, it will be interesting to see if they increasingly become consumers of web-based wait time information.

Atypical Internal Yellowing of Papaya Fruit in Hawaii Caused by Enterobacter sakazakii.

Internal yellowing (IY) caused by Enterobacter cloacae and characterized by yellow discolored tissue surrounding the papaya (Carica papaya L.) seed cavity, diffuse margins, and the presence of a distinctly rotten odor was first reported in 1987 (3). Here we report the formation of atypical internal yellowing (AIY) in ripe papaya caused by the bacterium Enterobacter sakazakii. In surveys conducted from 2006 to 2007, 'Kapoho Solo' papayas grown in the Puna District of Hawaii Island were obtained from various packinghouses. After incubation at 27°C, the papayas were bisected and examined for symptoms of IY. Among papayas that were asymptomatic for IY, a dull, greenish yellow discoloration of the flesh with a distinct margin extending from the seed cavity into the pericarp was noted, along with a pungent odor. These symptoms occurred in 5 of the 500 fruit surveyed and bacterial populations were 102 to 103 CFU/g. Discolored tissue was aseptically excised, weighed, macerated, serially diluted in sterile distilled water (SDW), and plated onto modified peptone yeast extract medium (PT-M4) (4). The plates were incubated at 30°C for 24 to 48 h until single colonies were evident. After 48 h, colonies on PT-M4 were orange-red, convex and circular, and surrounded by a somewhat opaque 1-mm margin. After single colony purification, five strains were obtained. The strains, inoculated into oxidation/fermentation-glucose tubes and API 20E strips (bioMerieux, Inc., Durham, NC) incubated at 30°C, were shown to be facultative anaerobes and identified as E. sakazakii with a 98.4% certainty. Colonies plated onto tryptic soy agar (TSA) and incubated for 72 h at 25°C produced yellow pigmentation, indicative of E. sakazakii. Amplification by PCR with E. sakazakii-specific primers (2) yielded a 929-bp fragment, which was absent with E. cloacae and Pseudomonas aeruginosa template DNA. To confirm pathogenicity, cell suspensions at 109 CFU/ml of putative E. sakazakii strains RK07-05, RK07-06, and RK07-07 and E. cloacae (3) were inoculated by injection (0.5 ml per site) into one-third-ripe 'Kapoho Solo' papayas (six fruit per strain, inoculated at duplicate sites) and incubated at 27°C for 4 days. Control sites were injected with 0.5 ml of SDW. Fruit inoculation experiments were repeated. E. cloacae-inoculated sites produced typical IY as previously described (3), while the sites inoculated with the three E. sakazakii strains produced greenish yellow tissue (26% mean incidence), symptomatic of AIY. Control sites did not produce IY or AIY. Koch's postulates were fulfilled, and the identification of reisolated bacterial strains was confirmed with API 20E, PCR, and pigment production on TSA. Although less prevalent (1% incidence) than the typical IY produced by E. cloacae (3), E. sakazakii has the potential to affect quality and food safety of fresh and processed papaya products. E. sakazakii has been implicated in a severe form of neonatal meningitis, sepsis, and necrotizing enterocolitis (1). Research into the transmission and infection of papaya of this cross-domain pathogen merits further study. References: (1) D. H. Adamson. Clin. Microbiol. Newsl. 3:19, 1981. (2) A. Lehner et al. BMC Microbiol. 4:43, 2004. (3) K. A. Nishijima et al. Plant Dis. 71:1029, 1987. (4) K. A. Nishijima et al. Plant Dis. 88:1318, 2004.

Depressed natural killer and lectin-induced cell-mediated cytotoxicity in cholesterol-fed guinea pigs.

Dunkin-Hartley and Hartley guinea pigs were fed a diet containing 1% cholesterol (C+) or a control diet (C-). The C+-fed guinea pigs showed a decrease in antitumor effector cell levels as measured by an in vitro 18-hour 51Cr release assay. Natural killer (NK) activity fell rapidly after initiation of cholesterol feeding, decreasing to 25.6% of control levels by 2 weeks. While the interferon inducer polyinosinic-polycytidylic acid increased NK activity as much as 3.6-fold in controls, the NK levels in C+-fed animals were not increased. NK activity was lower in both spleen and peripheral blood of C+-fed animals and against K562, MOLT-3, HL-60, and Raji target cells. Lectin-dependent cell-mediated cytotoxicity was increased in the C+-fed group over, the first 1-2 weeks on the diet, but it dropped to low levels by 6 weeks. Lipoprotein preparations from plasmas of both C+- and C--fed animals inhibited NK cell activity, but suppression was not due to lipoprotein cholesterol content. On the basis of lipoprotein protein, lipoproteins from C--fed animals were more suppressive. The results suggest that the decrease in cytotoxicity induced by dietary cholesterol is due to more than the high levels of plasma and lipoprotein cholesterol.

Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma.

Post-traumatic cystic cavitation, in which the size and severity of a CNS injury progress from a small area of direct trauma to a greatly enlarged secondary injury surrounded by glial scar tissue, is a poorly understood complication of damage to the brain and spinal cord. Using minimally invasive techniques to avoid primary physical injury, this study demonstrates in vivo that inflammatory processes alone initiate a cascade of secondary tissue damage, progressive cavitation, and glial scarring in the CNS. An in vitro model allowed us to test the hypothesis that specific molecules that stimulate macrophage inflammatory activation are an important step in initiating secondary neuropathology. Time-lapse video analyses of inflammation-induced cavitation in our in vitro model revealed that this process occurs primarily via a previously undescribed cellular mechanism involving dramatic astrocyte morphological changes and rapid migration. The physical process of cavitation leads to astrocyte abandonment of neuronal processes, neurite stretching, and secondary injury. The macrophage mannose receptor and the complement receptor type 3 beta2-integrin are implicated in the cascade that induces cavity and scar formation. We also demonstrate that anti-inflammatory agents modulating transcription via the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma may be therapeutic in preventing progressive cavitation by limiting inflammation and subsequent secondary damage after CNS injury.

The BH3 domain is required for caspase-independent cell death induced by Bax and oligomycin.

Bax causes apoptosis by associating with mitochondria and triggering cytochrome c release, which activates the caspase cascade. Bax can also kill some cells independently of caspases, but the requirements for such killing are poorly understood. Here we describe an inducible fibroblast line that expresses Bax when tetracycline is withdrawn; the resulting apoptosis can be blocked by the caspase inhibitor zVAD-fmk. Even when caspases are inhibited, however, treating the Bax-expressing cells with the mitochondrial toxin oligomycin efficiently triggers death with features resembling apoptosis. Bax mutants lacking the BH3 domain remain able to cause cytochrome c release and caspase-mediated death, but cannot support this caspase-independent killing. Mutating specific BH3 residues needed for binding Bcl2 does not prevent synergy with oligomycin, implying that no such binding is required. These findings illuminate a caspase-independent pathway of death that depends on the Bax BH3 domain and on effectors emanating from mitochondria.

Patient preferences for oral versus intravenous palliative chemotherapy.

PURPOSE: To assess patient preference for oral versus intravenous (i.v.) palliative chemotherapy (CT). A strong preference would be an important quality-of-life issue. PATIENTS AND METHODS: A structured interviewer-administered scenario-based questionnaire evaluated incurable cancer patients who would be likely to receive palliative CT in the future. Using probability trade-offs, the preference for route of administration was evaluated against diminishing treatment response. RESULTS: Of 103 assessable patients, 92 preferred oral CT, 10 preferred i.v. CT, and one had no preference. Patient preferences were not associated with age, sex, site of primary cancer, or previous CT experiences. Major reasons for preferring oral CT were convenience, problems with i.v. access or needles, and a better CT-taking environment (outside of the clinic). Regardless of initial preference, 70% of patients were not willing to accept a lower response rate and 74% were not willing to accept a shorter duration of response to retain their initial preference. Although 99% of patients had a preference, 39% wanted the specific treatment decision made primarily by their physicians, 38% primarily by themselves, and 22% shared equally. CONCLUSION: Patients with incurable cancer have a clear preference for oral CT, but are generally not willing to sacrifice efficacy for their preference. Almost 40% of patients did not want to make final treatment decisions themselves.

High-fiber diets: influence on characteristics of cecal digesta including short-chain fatty acid concentrations and pH.

The effects of two sources of dietary fiber on the characteristics of cecal contents were assessed directly with miniature swine cannulated to facilitate frequent collections of cecal digesta. The short-chain fatty acid (SCFA) concentrations increased and the pH decreased at the same time that meal constituents entered the cecum; PEG was used as a dietary marker. The bean diet resulted in higher concentrations of acetate and total SCFA in cecal digesta, lower concentrations of butyrate, a larger SCFA pool size, and a more acidic pH than did the bran diet. Thus, we conclude that SCFA concentrations and acidity of the digesta are directly related and that dietary fibers can affect simultaneously several variables that are implicated as factors influencing colonic health.

Resin-purified digoxigenin-labeled DNA probes: an efficient protocol for mapping and fingerprinting sugarcane.

Nonradioactive Southern blotting using digoxigenin (DIG) has become routinely applied to the analysis of single-copy genes for genetic mapping because it is fast and safe. Previous studies indicate that DIG-labeled probes are suitable for single-gene detection in less complex genomes, but their efficient application to mapping a large octoploid genome has not been discussed. We developed a stream-lined procedure for nonradioactive restriction fragment length polymorphism mapping and DNA fingerprinting of sugarcane that combines DIG-11-dUTP and anion-exchange chromatography. In this report, we show that anion-exchange chromatography provides a reliable and simple technique for the resin-purification of large numbers of DIG-labeled DNA fragments 0.3-3.0 kb in size, and it is essential in minimizing contaminants and nonspecific signal.

Prevalence and correlates of family dysfunction and poor adjustment to chronic illness in specialty clinics.

This study estimated the prevalence of poor adjustment and family dysfunction among three chronically ill clinic patient populations and assessed the biological, situational, social and psychological variables which most explained poor adjustment. Recently referred subjects were approached and 216 chronically ill subjects (from oncology, rheumatology and gastroenterology clinics) completed a Meaning of Illness Questionnaire, the McMaster Family Assessment Device, and the Psychosocial Adjustment to Illness Self-report Scale. In addition, information describing their biological, disease and socioeconomic status was obtained from the clinic record. Respondents were generally representative of other new referrals to the clinics (ineligible for the subsequent trial) in disease characteristics but uniformly came from a more advantaged socioeconomic situation and were better adjusted to illness. Subjects from the three clinics were comparable on meaning, family function and adjustment variables. The proportion of subjects with family dysfunction was 30% and with poor adjustment to illness was 36%, high by community standards. Nevertheless, healthy family functioning and high levels of positive adjustment to chronic illness prevailed and were remarkably similar across clinic settings. Severity or type of disease was not related to adjustment outcomes nor to the level of observed disability. Rather, as hypothesized, meaning given the illness, followed by family function, and disability variables combined to explain 57% of the variance in adjustment outcomes. An intervention designed to improve family function and the meaning given illness was judged suitable.

Predicting psychological distress in patients with cancer: conceptual basis and reliability evaluation of a self-report questionnaire.

UNLABELLED: BACKGROUND/MATERIALS AND METHODS: A battery of instruments intended to predict the likelihood of future psychosocial distress in patients with cancer was developed and tested. The battery consists of newly-developed items for constructs relating to social support and to past coping experiences. Embedded within the past coping items are items on future illness-dependent expectations. The battery also incorporates previously developed instruments for recent stressful life events (Sarason) and the presence of anxiety or depression (SCL-90-R). The reliability of the entire instrument was determined in 2 similar groups of patients with cancer. RESULTS: The illness-dependent expectations items were stable and internally consistent. The past coping and social support items possessed stability, but did not possess sufficient internal consistency for either to be used as a scale. The recent stressful life event scores were not stable in either patient group over the two week retest interval. For the SCL-90-R, internal consistencies and stability coefficients are acceptable for all symptom dimensions with the exception of the stability coefficient for hostility.

Decreased UV sensitivity, mismatch repair activity and abnormal cell cycle checkpoints in skin cancer cell lines derived from UVB-irradiated XPA-deficient mice.

Xeroderma pigmentosum group A gene (XPA)-deficient mice are defective in nucleotide excision repair (NER) and are therefore highly sensitive to ultraviolet (UV)-induced skin carcinogenesis. We established cell lines from skin cancers of UVB-irradiated XPA-deficient mice to investigate the phenotypic changes occurring during skin carcinogenesis. As anticipated, the skin cancer cell lines were devoid of NER activity but were less sensitive to killing by UV-irradiation than the XPA(-/-) fibroblast cell line. The lines were also more resistant to 6-thioguanine (6-TG) than XPA(-/-) and XPA(+/+) fibroblasts, which was suggestive of a mismatch repair (MMR) defect. Indeed, in vitro mismatch binding and MMR activity were impaired in several of these cell lines. Moreover, these cell lines displayed cell cycle checkpoint derangements following UV-irradiation and 6-TG exposure. The above findings suggest that MMR downregulation may help cells escape killing by UVB, as was seen previously for methylating agents and cisplatin, and thus that MMR deficient clones are selected for during the tumorigenic transformation of XPA(-/-) cells.