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Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one‐time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty‐six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z‐scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (−1.09 ± 1.53 versus −1.27 ± 1.25, p = 0.549). LS BMD Z‐scores declined from baseline to 12 months in children with ON (−0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z‐scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (−1.77 ± 1.22) compared to those without (−1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z‐scores were lower in children with ON (hip −0.98 ± 0.95 versus −0.28 ± 1.06, p = 0.010; TB −1.36 ± 1.10 versus −0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15–2.13; p = 0.004), and hip BMD Z‐score at MRI (OR 2.23; 95% CI, 1.02–4.87; p = 0.046) were independently associated with ON. Overall, one‐third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z‐scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z‐scores at MRI were significantly associated with prevalent, off‐therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Many commercially available dermatologic lasers utilize cryogen spray cooling for epidermal protection. A previous tissue culture study demonstrated that single cryogen spurts (SCS) of 80 ms or less were unlikely to cause cryo-injury in light-skinned individuals. More recently, multiple cryogen spurts (MCS) have been incorporated into commercial devices, but the effects of MCS have not been evaluated. The aim was to study an in vitro tissue culture model and the epidermal and dermal effects of SCS vs patterns of shorter MCS with the same preset total cryogen delivery time (Deltat(c)) and provide an explanation for noted differences. Four different spurt patterns were evaluated: SCS: one 40-ms cryogen spurt; MCS2: two 20-ms cryogen spurts; MCS4: four 10-ms cryogen spurts; MCS8: eight 5-ms cryogen spurts. Actual Deltat(c) and total cooling time (Deltat(Total)) were measured for each spurt pattern. RAFT tissue culture specimens were exposed to cryogen spurt patterns and biopsies were taken immediately and at days 3 and 7. Actual Deltat(c) was increased while Deltat(Total) remained relatively constant as the preset Deltat(c) of 40 ms was delivered as shorter MCS. Progressively more epidermal damage was noted with exposure to the MCS patterns. No dermal injury was noted with either SCS or MCS. For a constant preset Deltat(c) of 40 ms, delivering cryogen in patterns of shorter MCS increased the actual Deltat(c) and consequently the observed epidermal cryo-injury as compared to an SCS.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.

Background and objectivesCryogen spray cooling (CSC) is commonly used during dermatologic laser surgery. The epidermal and dermal effects of CSC have not been adequately evaluated. To study the potential for epidermal and dermal injury after CSC using an in vitro model of human skin (RAFT).Study design/materials and methodsRAFT specimens were exposed to continuous CSC spurt durations of 10, 20, 40, 80, 100, 200, or 500 milliseconds. Biopsies were taken acutely, 3 and 7 days post-CSC exposure. Sections were stained with hematoxylin and eosin for evaluation of possible injury, Ki-67 to determine keratinocyte viability, and Melan-A, to identify and evaluate melanocytes.ResultsMinimal, transient epidermal changes were noted in specimens exposed to continuous CSC spurts of 80 milliseconds or less. Keratinocytes and melanocytes remained viable. Continuous CSC spurts of 100, 200, or 500 milliseconds (much longer than recommended for clinical use) resulted in significant epidermal injury acutely, with partial or full thickness epidermal necrosis at 7 days. Only the 500 milllisecond specimen demonstrated dermal change, decreased fibroblast proliferation at 3 days.ConclusionsContinuous CSC spurts of 80 milliseconds or less induce minimal, if any, epidermal or dermal damage and are unlikely to produce cryo-injury when used during dermatologic laser surgery.

BackgroundThe antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque.MethodsBiopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied.ResultsDespite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment.ConclusionsIt appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed.

Objective To examine, for essential anti-cancer medicines, the alignment of national lists of essential medicine's and national reimbursable medicines lists with the World Health Organization's (WHO's) Model Lists. Methods National medicine lists for 135 countries with per-capita gross national incomes below 25 000 United States dollars in 2015 were compared with WHO's 2013 and 2015 Model Lists of Essential Medicines. Correlations between numbers of anti-cancer medicines included in national lists and gross national income (GNI), government health expenditure and number of physicians per 1000 population were evaluated. Findings Of the 25 anti-cancer medicines on the 2013 Model List and the 16 added via the 2015 revision of the Model List, 0-25 (median: 17) and 0-15 (median: 3) appeared in national lists, respectively. There was considerable variability in these numbers within and between World Bank income groups. Of the 16 new medicines included in the 2015 Model List, for example, 0-10 (median: 1) and 2- 15 (median: 10) were included in the national lists of low-income and high-income countries, respectively. The numbers of these new medicines included in national lists were significantly correlated (P [less than or equal to] 0.0001) with per-capita GNI (r=0.45), per- capita annual government health expenditure [r = 0.33) and number of physicians per 1000 population (r=0.48). Twenty-one countries (16%) included the targeted anti-cancer medicines imatinib, rituximab and trastuzumab in their national lists. Conclusion Substantial numbers of anti-cancer medicines are included in national lists of low- and middle-income countries but the availability, affordability, accessibility and administration feasibility of these medicines, at country-level, need assessment. Objectif Examiner, en ce qui concerne les medicaments essentiels pour traiter le cancer, la conformite des listes nationales de medicaments essentiels et des listes nationales de medicaments remboursables avec les Listes modeles de l'Organisation mondiale de la Sante (OMS). Methodes Les listes nationales de medicaments de 135 pays dont le revenu national brut par habitant etait inferieur a 25 000 dollars des Etats-Unis en 2015 ont ete comparees aux Listes modeles de medicaments essentiels de 2013 et 2015 de l'OMS. Nous avons mis en correlation le nombre de medicaments pour traiter le cancer inclus dans les listes nationales avec le revenu national brut (RNB), les depenses publiques de sante et le nombre de medecins pour 1000 habitants. Resultats Sur les 25 medicaments pour traiter le cancer inclus dans la Liste modele de 2013, 0-25 (mediane: 17) apparaissaient sur les listes nationales, et sur les 16 ajoutes lors de la revision de la Liste modele de 2015, 0-15 (mediane 3) figuraient sur les listes nationales. Ces chiffres etaient tres variables au sein des groupes de revenus de la Banque mondiale et entre eux. Ainsi, sur les 16 nouveaux medicaments inclus dans la Liste modele de 2015, 0-10 (mediane: 1) apparaissaient sur les listes nationales des pays a faible revenu et 2-15 (mediane: 10) sur celles des pays a revenu eleve. Le nombre de nouveaux medicaments figurant sur les listes nationales etait significativement correle (P < 0,0001) avec le RNB par habitant (r=0,45), les depenses annuelles de sante par habitant engagees par le gouvernement (r=0,33) et le nombre de medecins pour 1000 habitants (r=0,48). L'imatinib, le rituximab et le trastuzumab, trois medicaments utilises pour traiter le cancer, apparaissaient sur la liste nationale de vingt-et-un pays (16%). Conclusion Un nombre important de medicaments pour traiter le cancer est inclus dans les listes nationales des pays a revenu faible et intermediaire, mais il convient d'evaluer la disponibilite, le caractere economiquement abordable, l'accessibilite et la faisabilite administrative de ces medicaments au niveau des pays. Objetivo Examinar, en terminos de los medicamentos esenciales contra el cancer, la coherencia de las listas nacionales de medicamentos esenciales y las listas nacionales de farmacos reembolsares con las Listas Modelo de la Organizacion Mundial de la Salud (OMS). Metodos En 2015, se compararon las listas nacionales de medicamentos de 135 paises con un producto interior bruto per capita inferiora 25 000 dolares estadounidenses con las Listas Modelo de Medicamentos Esenciales de la OMS de 2013 y 2015. Se evaluaron las correlaciones entre los numeros de medicamentos contra el cancer incluidos en las listas nacionales y el producto interior bruto (PIB), el gasto sanitario publico y el numero de medicos por cada 1 000 habitantes. Resultados De los 25 medicamentos contra el cancer de la Lista Modelo de 2013 y los 16 que se anadieron en la revision de 2015 de la Lista Modelo, 0-25 (promedio: 17) y 0-15 (promedio: 3) aparecian en las listas nacionales, respectivamente. Hubo una variabilidad considerable en estos numeros dentro y entre los grupos de ingresos del Banco Mundial. De los 16 nuevos medicamentos incluidos en la Lista Modelo de 2015, por ejemplo, se incluyeron 0-10 (promedio: 1) y 2-15 (promedio: 10) en las listas nacionales de paises con ingresos bajos y con ingresos altos, respectivamente. Los numeros de estos nuevos medicamentos incluidos en las listas nacionales tenian una gran correlacion (P < 0,0001) con el PIB per capita (r=0,45), el gasto sanitario publico anual per capita (r=0,33) y el numero de medicos por cada 1 000 habitantes (r=0,48). Veintiun paises (16%) incluian en sus listas nacionales los medicamentos contra el cancer imatinib, rituximab y trastuzumab. Conclusion Se han incluido numerosos medicamentos contra el cancer en listas nacionales de paises con ingresos bajos y medios, aunque la disponibilidad, asequibilidad, acceso y viabilidad de administracion de los mismos necesitan una evaluacion a nivel del pais., Introduction Effective treatment of cancer relies on early detection, accurate diagnosis and access to surgery, chemotherapy and/or radiotherapy. The provision of affordable access to cytotoxic medicines is a major challenge [...]

Curriculum planning for the development of graphicacy capability has not been systematically included in general education to coincide with the graphicacy needs of human society. In higher education, graphicacy curricula have been developed to meet the needs of certain disciplines, for example medical and teacher training and engineering, among others. A framework for graphicacy curricula, anticipating the graphicacy needs in higher education, has yet to be strategically planned for general education. This is partly a result of lack of research effort in this area, but also a result of lack of systematic curriculum planning in general. This paper discusses these issues in the context of graphicacy curricula for engineering. The paper presents three broad individual case studies spanning Europe and the USA, brought together by the common denominator, graphicacy. The case studies are based on: an analysis of graphicacy within general education curricula, an analysis of graphicacy for engineering education in Europe and an analysis of graphicacy for engineering education in the USA. These three papers were originally presented in a plenary session at the American Society for Engineering Education, Engineering Design Graphics Division at the University of Limerick in November 2012. The case studies demonstrate the potential for strategic curriculum planning in regard to the development of graphicacy in general education and an overview of a methodology to achieve that. It also offers further evidence towards the importance of the systematic classification of graphics capabilities in Engineering and how the lack of a developed theoretical framework in this area undermines the case for the importance of graphics within engineering education.