Impact of Altitude-based Hemoglobin Modification on Pediatric Iron Deficiency Anemia Screening.

OBJECTIVE: To determine if additional children attending primary care clinics in moderate-altitude areas would screen positive for anemia if the hemoglobin cutoff were modified for altitude. STUDY DESIGN: This cross-sectional study evaluated children aged 11-19 months of age who had a screening hemoglobin conducted between January 2011 and December 2017 at 4 moderate-altitude (1726-2212 m) and 8 low-altitude (1-20 m) US military clinics. The primary outcome was anemia prevalence (hemoglobin <11 g/dL) in moderate-altitude and low-altitude groups, before and after applying the current World Health Organization model for altitude-based hemoglobin modification. Groups were compared with prevalence ORs adjusted for age, sex, weight-for-length percentile, and parental military rank, and the false-negative proportion was calculated for children with anemia at moderate altitude. RESULTS: Before altitude modification, anemia prevalence was 4.4% in the moderate-altitude group (n = 1488) and 16.8% in the low-altitude group (n = 7090) (prevalence OR, 0.23; 95% CI, 0.17-0.29). After applying the World Health Organization model, anemia prevalence in the moderate-altitude group increased to 14.7% (prevalence OR, 0.82; 95% CI, 0.70-0.97). Nonapplication of the model at moderate altitude resulted in a false-negative proportion of 0.70 (95% CI, 0.63-0.76). CONCLUSIONS: Nonuse of the World Health Organization altitude-based modification model for hemoglobin may result in a large percentage of US children with anemia at moderate altitude screening falsely negative for anemia. Although ancestry disparities in altitude acclimatization may limit universal application of the current World Health Organization model, the existing standard of care may leave children at moderate altitude at risk for complications from iron deficiency anemia.

High activation and skewed T cell differentiation are associated with low IL-17A levels in a hu-PBL-NSG-SGM3 mouse model of HIV infection.

The humanized NOD/SCID/IL-2 receptor γ-chainnull (NSG) mouse model has been widely used for the study of HIV pathogenesis. Here, NSG mice with transgenic expression of human stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 (NSG-SGM3) were injected with peripheral blood leukocytes (PBL mice) from two HIV-infected (HIV+ ) patients who were under anti-retroviral therapy (ART; referred as HIV+ mice) or one HIV-seronegative healthy volunteer (HIV- ). Such mice are either hu-PBL-NSG-SGM3 HIV+ or HIV- mice, depending on the source of PBL. The kinetics of HIV replication and T cell responses following engraftment were evaluated in peripheral blood and secondary lymphoid tissues. High HIV replication and low CD4 : CD8 ratios were observed in HIV+ mice in the absence of anti-retroviral therapy (ART). Consistent with high activation and skewed differentiation of T cells from the HIV-infected donor, HIV+ mice exhibited a higher T cell co-expression of human leukocyte antigen D-related (HLA-DR) and CD38 than HIV- mice, as well as a shifted differentiation to a CCR7- CD45RA+ terminal effector profile, even in the presence of ART. In addition, HIV replication and the activation/differentiation disturbances of T cells were associated with decreased plasma levels of IL-17A. Thus, this hu-PBL-NSG-SGM3 mouse model recapitulates some immune disturbances occurring in HIV-infected patients, underlying its potential use for studying pathogenic events during this infection.

The Anti-cancer Activity of Vernonia divaricata Sw against Leukaemia, Breast and Prostate Cancers In Vitro.

BACKGROUND: Vernonia divaricata is one of five endemic Vernonia species of Jamaica. The ethno-medicinal uses of other species have been established, however, scientific validation of this species has not yet been done and as such this paper is aimed at identifying the anti-cancer activity of V divaricata against leukaemia, breast and prostate cancer cell lines. METHODS: Leaves and stems of V divaricata were dried and milled into powder. The crude hexane and methanol extracts of the leaves and stems were obtained and bio-assayed using WST-1 cell proliferation assay against leukaemia, breast and prostate cancer cell lines. RESULTS: The crude hexane and methanol extracts of V divaricata were able to significantly retard the growth of the MCF-7 (breast), HL-60 (leukaemia) and the PC-3 (prostate) cancer cell lines. The crude methanol extract of the stem was the strongest, exhibiting anti-proliferation activity with IC50 values of 10.14, 12.63 and 9.894 µg/ml for the HL-60, MCF-7 and PC-3 cancer cell lines, respectively, with the most potent toward prostate cancer. CONCLUSION: The medicinal use of V divaricata as an anti-cancer agent was corroborated as the crude hexane and methanol extracts demonstrated potent anti-proliferation activity and as such hold potential for further research and development into a drug to prevent or treat various cancers.

Estimating the density of femoral head trabecular bone from hip fracture patients using computed tomography scan data.

The purpose of this study was to compare computed tomography density (ρCT ) obtained using typical clinical computed tomography scan parameters to ash density (ρash ), for the prediction of densities of femoral head trabecular bone from hip fracture patients. An experimental study was conducted to investigate the relationships between ρash and ρCT and between each of these densities and ρbulk and ρdry . Seven human femoral heads from hip fracture patients were computed tomography-scanned ex vivo, and 76 cylindrical trabecular bone specimens were collected. Computed tomography density was computed from computed tomography images by using a calibration Hounsfield units-based equation, whereas ρbulk, ρdry and ρash were determined experimentally. A large variation was found in the mean Hounsfield units of the bone cores (HUcore) with a constant bias from ρCT to ρash of 42.5 mg/cm3. Computed tomography and ash densities were linearly correlated (R 2 = 0.55, p < 0.001). It was demonstrated that ρash provided a good estimate of ρbulk (R 2 = 0.78, p < 0.001) and is a strong predictor of ρdry (R 2 = 0.99, p < 0.001). In addition, the ρCT was linearly related to ρbulk (R 2 = 0.43, p < 0.001) and ρdry (R 2 = 0.56, p < 0.001). In conclusion, mineral density was an appropriate predictor of ρbulk and ρdry , and ρCT was not a surrogate for ρash . There were linear relationships between ρCT and physical densities; however, following the experimental protocols of this study to determine ρCT , considerable scatter was present in the ρCT relationships.

In vitro and In vivo anti-cancer effects of Tillandsia recurvata (Ball Moss) from Jamaica / Efectos Anticancerosos In vitro e In vivo de la Tillandsia recurvata (Bola de Musgo) de Jamaica

OBJECTIVE: Tillandsia recurvata, also commonly known as Ball Moss, is endemic to Jamaica and some parts of the Caribbean and South America. The plant, despite being reported to be used in folk medicine, had not previously been evaluated for its anti-cancer potential. The aim of this study was to evaluate the anti-cancer activity of Ball Moss. METHODS: The anti-proliferation activity of the crude methanolic extract of the T recurvata was evaluated in vitro in five different histogenic cancer cell lines (prostate cancer - PC-3, breast cancer, Kaposi sarcoma, B-16 melanoma and a B-cell lymphoma from a transgenic mouse strain) using the trypan blue assay. The crude extract was also evaluated in vivo in tumour-bearing mice. Immunohistochemistry staining with Apoptag was used for histology and determination of apoptosis. RESULTS: The crude methanolic extract of T recurvata demonstrated anti-proliferation activity against all the cell lines, killing > 50% of the cells at a concentration of 2.5 µg/ml. Kaposi sarcoma xenograft tumours were inhibited by up to 75% compared to control in the in vivo study (p < 0.05). There was evidence of DNA fragmentation and a decrease in cell viability on histological studies. The methanolic extract showed no toxic effect in the mice at a dose of 200 mg/kg. CONCLUSIONS: Our data suggest that T recurvata has great potential as an anti-cancer agent and that one of its mechanisms of cell kill and tumour inhibition is by the induction of apoptosis.

OBJETIVO: La Tillandsia recurvata, también conocida como bola de musgo, es endémica en Jamaica, así como en algunas partes del Caribe y América del sur. Si bien se había reportado su uso como parte de la medicina popular, esta planta no había sido evaluada previamente en relación con su potencial para la lucha contra el cáncer. El objetivo de este estudio fue evaluar la actividad anticancerígena de la bola de musgo. MÉTODOS: La actividad antiproliferativa del extracto metanólico crudo de la T recurvata, fue evaluada in vitro en cinco líneas celulares diferentes de cáncer histogenético (cáncer de próstata - PC-3, cáncer de mama, sarcoma de Kaposi, melanoma B-16 y un linfoma de células B de una cepa de ratón transgénico) usando el ensayo con azul de tripano. El extracto crudo también se evaluó in vivo en ratones portadores de tumor. La tinción inmunohistoquímica con ApopTag fue utilizada para la histología y determinación de la apoptosis. RESULTADOS: El extracto metanólico crudo de T recurvata demostró la actividad proliferativa frente a todas las líneas celulares, matando > 50% de las células a una concentración de 2,5 µg/ml. Los tumores de xenoinjerto de sarcoma de Kaposi fueron inhibidos hasta un 75% en comparación con el control en el estudio in vivo (p < 0.05). Hubo evidencia de fragmentación de DNA y una disminución en la viabilidad celular en los estudios histológicos. El extracto metanólico no mostró ningún efecto tóxico en los ratones a dosis de 200 mg/kg. CONCLUSIONES: Nuestros datos sugieren que la T recurvata tiene gran potencial como agente anticanceroso, y que uno de sus mecanismos de inhibición de tumores y muerte de las células tiene lugar mediante la inducción de la apoptosis.

In vitro and in vivo anti-cancer effects of tillandsia recurvata (ball moss) from Jamaica.

OBJECTIVE: Tillandsia recurvata, also commonly known as Ball Moss, is endemic to Jamaica and some parts of the Caribbean and South America. The plant, despite being reported to be used in folk medicine, had not previously been evaluated for its anti-cancer potential. The aim of this study was to evaluate the anti-cancer activity ofBall Moss. METHODS: The anti-proliferation activity of the crude methanolic extract of the T recurvata was evaluated in vitro in five different histogenic cancer cell lines (prostate cancer - PC-3, breast cancer Kaposi sarcoma, B-16 melanoma and a B-cell lymphoma from a transgenic mouse strain) using the trypan blue assay. The crude extract was also evaluated in vivo in tumour-bearing mice. Immunohistochemistry staining with Apoptag was used for histology and determination of apoptosis. RESULTS: The crude methanolic extract of T recurvata demonstrated anti-proliferation activity against all the cell lines, killing > 50% of the cells at a concentration of 2.5 microg/ml. Kaposi sarcoma xenograft tumours were inhibited by up to 75% compared to control in the in vivo study (p < 0.05). There was evidence of DNA fragmentation and a decrease in cell viability on histological studies. The methanolic extract showed no toxic effect in the mice at a dose of 200 mg/kg. CONCLUSIONS: Our data suggest that T recurvata has great potential as an anti-cancer agent and that one of its mechanisms of cell kill and tumour inhibition is by the induction of apoptosis.

Generation of activated natural killer (A-NK) cells in patients with chronic myelogenous leukaemia and their role in the in vitro disappearance of BCR/abl-positive targets.

Activated natural killer (A-NK) cells, a subset of CD56(dim)CD3- lymphocytes, are obtained from PBMC of normal donors by adherence to plastic and culture in the presence of IL2. In this study we tested the feasibility of generating A-NK cells in patients with Ph+ chronic myeloid leukaemia (CML). Cultures obtained from patients with early chronic phase (ECP; n=7) contained a mean (+/-SD) of83 +/- 7% of CD3- cells, and those from patients with advanced chronic phase (ACP; n=7) contained 27+/-33% CD56+CD3- cells. In three patients with leukaemia in a blastic phase (BP) it was only possible to obtain one culture enriched in CD56+CD3- cells (81%). Cellular aggregates of myeloid cells and large granular lymphocytes were observed in early A-NK cell cultures. Paired freshly-adherent and cultured A-NK cells were tested for the presence of BCR/abl mRNA by RT-PCR. The BCR/abl+ cells were detected in all 12 preparations of the freshly adherent A-NK cells tested. In 6/12 the BCR/abl+ cells were no longer detectable by RT-PCR on day 14 of culture. Both proliferation and antileukaemic cytotoxicity were significantly higher (P=0.002 and P=0.029, respectively) in the BCR/abl- cultures than those in the six BCR/abl+ cultures. 5/6 BCR/abl- cultures were highly enriched in A-NK cells on day 14, and 1/6 contained predominantly CD56+CD3+ cells. Only 2/6 BCR/abl + cultures were enriched in A-NK cells on day 14, but they had poor cytotoxicity and a low proliferative index. Myeloid cells (CD33+) were more frequently detected in the BCR/abl+ than BCR/abl- A-NK cell cultures (P=0.028). These observations suggest that: (1) populations of benign A-NK cells can be generated from the peripheral blood of CML patients; (2) the ability to generate A-NK cells is impaired in patients with advanced CML; and (3) the ability to generate A-NK cells with antileukaemic activity correlates with the disappearance of BCR/abl+ cells from these cultures.

Preparation of viable tumour cell vaccine from human solid tumours: relationship between tumour mass and cell yield. The Tissue Bank, Pittsburgh Cancer Institute.

Active specific immunotherapy for cancer often requires the use of autologous or allogeneic tumour cells as immunizing antigen. Tumours were obtained for such a protocol. However, estimation of viable cell yield from pre-processed fresh tumour mass was difficult, and initially there did not appear to be a direct relationship between pre-processed tumour mass and viable cells obtained after processing. We therefore analysed all of 293 tumour specimens processed to attempt to discern such a relationship. Of these 137 were melanoma, 14 were sarcoma, 48 were adenocarcinoma, 59 were renal cell carcinoma and 35 were classified as other. A positive correlation was found between pre-processed tumour mass and viable cell yield, with Spearman correlation values varying from r = 0.49 (adenocarcinoma) to r = 0.84 (melanoma). For all tumours the Spearman correlation was r = 0.70 (p = 0.0001). Not surprisingly, the most frequent site of removal associated with bacterial contamination was bowel. In conclusion, this study provides useful curves for predicting viable tumour cell yield from pre-processed tumour mass of given histology.