Approximately 10% of Ashkenazi Jewish (AJ) women with breast cancer (BC) carry a founder mutation in
BRCA1
or
BRCA2
. There is an association between
BRCA1
mutations and “triple-negative” breast ...cancer (TNBC) estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative. We sought to determine the predictive value of the TNBC phenotype for the presence of a
BRCA
mutation in AJ women ascertained without respect to family history. DNA samples were collected between 8/2000 and 6/2004 from a prevalent cohort of unselected AJ women with breast cancer (median age at diagnosis 56 years). Samples (
n
= 451) were genotyped for AJ founder mutations. 352 (78.0%) cancers were ER positive, 254 (56.3%) PR positive, and 91 (20.2%) ER negative/PR negative. 63 (14.0%) cancers were HER2 positive (immunohistochemistry 3+ or FISH >2.2). TNBC was observed in 64 patients (14.2%). Founder mutations were detected in 48 samples (10.6%) including 25/64 TNBC (39.1%; 19
BRCA1
, 6
BRCA2
). Among TNBC patients with family history (FH) information, 6/15 (40%) mutations were found in women without breast or ovarian cancer in a close relative. The positive predictive value of TNBC for a
BRCA1
mutation was 30% overall, 50% in women diagnosed<50 years, and 14% in women diagnosed ≥50. TNBC was significantly associated with detecting a mutation in either
BRCA1
or
BRCA2
, but only 25/52 (48%) mutation-associated cancers were TNBC. The prevalence of
BRCA
founder mutations exceeds 50% in subsets of AJ women with TNBC. FH is an imperfect predictor of mutation status in this group. A significant number of mutation-associated TNBC are due to
BRCA2
.
Curly hair is reported to contain higher lipid content than straight hair, which may influence incorporation of lipid soluble drugs. The use of race to describe hair curl variation (Asian, Caucasian ...and African) is unscientific yet common in medical literature (including reports of drug levels in hair). This study investigated the reliability of a geometric classification of hair (based on 3 measurements: the curve diameter, curl index and number of waves).
After ethical approval and informed consent, proximal virgin (6cm) hair sampled from the vertex of scalp in 48 healthy volunteers were evaluated. Three raters each scored hairs from 48 volunteers at two occasions each for the 8 and 6-group classifications. One rater applied the 6-group classification to 80 additional volunteers in order to further confirm the reliability of this system. The Kappa statistic was used to assess intra and inter rater agreement.
Each rater classified 480 hairs on each occasion. No rater classified any volunteer's 10 hairs into the same group; the most frequently occurring group was used for analysis. The inter-rater agreement was poor for the 8-groups (k = 0.418) but improved for the 6-groups (k = 0.671). The intra-rater agreement also improved (k = 0.444 to 0.648 versus 0.599 to 0.836) for 6-groups; that for the one evaluator for all volunteers was good (k = 0.754).
Although small, this is the first study to test the reliability of a geometric classification. The 6-group method is more reliable. However, a digital classification system is likely to reduce operator error. A reliable objective classification of human hair curl is long overdue, particularly with the increasing use of hair as a testing substrate for treatment compliance in Medicine.
An experimental study was undertaken on the preparation, by High Energy Reactive Ball Milling in Hydrogen (HRBM), of hydrogen storage materials on the basis of Mg mixed with FeTiO sub(3), and their ...further characterisation (SEM, TEM, XRD, volumetric H sub(2) absorption studies, TDS). It was shown that the addition of > or =, slanted5 wt.% of FeTiO sub(3) dramatically improves H absorption in Mg and reduces the temperature of further H desorption. Subsequent addition of carbon, including Graphite (G), Activated Carbon (AC) and Multi-Wall Carbon Nanotubes (MWCNT) results in some slowing of the H absorption down but significantly improves re-hydrogenation performances of the material, which in time is able to re-absorb about 5 wt.% H in less than 5-7 min (15 bar H sub(2)/250 degreesC). These improvements were associated with the reduction of FeTiO sub(3) to yield nanopartides of Fe and TiFe(Hx).
Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases causing hyperammonemic encephalopathy. Despite intensive dietary and pharmacological therapy, outcome is poor in a subset ...of UCD patients. Reducing ammonia production by changing faecal microbiome in UCD is an attractive treatment approach. We compared faecal microbiome composition of 10 UCD patients, 10 healthy control subjects and 10 phenylketonuria (PKU) patients. PKU patients on a low protein diet were included to differentiate between the effect of a low protein diet and the UCD itself on microbial composition. Participants were asked to collect a faecal sample and to fill out a 24 h dietary journal. DNA was extracted from faecal material, taxonomy was assigned and microbiome data was analyzed, with a focus on microbiota involved in ammonia metabolism.
In this study we show an altered faecal microbiome in UCD patients, different from both PKU and healthy controls. UCD patients on dietary and pharmacological treatment had a less diverse faecal microbiome, and the faecal microbiome of PKU patients on a protein restricted diet with amino acid supplementation showed reduced richness compared to healthy adults without a specific diet. The differences in the microbiome composition of UCD patients compared to healthy controls were in part related to lactulose use. Other genomic process encodings involved in ammonia metabolism, did not seem to differ. Since manipulation of the microbiome is possible, this could be a potential treatment modality. We propose as a first next step, to study the impact of these faecal microbiome alterations on metabolic stability.
The faecal microbiome of UCD patients was less diverse compared to PKU patients and even more compared to healthy controls.
Mourning in America Zeavin, Lynne; McClure, Mary Margaret; Hamer, Forrest ...
Journal of the American Psychoanalytic Association,
10/2022, Letnik:
70, Številka:
5
Journal Article
Jane Caflisch's discussion (this issue) of white liberal guilt is recognized as a bold and ground-breaking exploration of how the Kleinian concepts of paranoid-schizoid and depressive positions may ...shed light on the question of reparation for racial injustice. I suggest that, in addition to persecutory and depressive guilt, melancholic guilt also operates in racist mind-sets, and constitutes the more serious obstacle to reparation. Guilt of this sort prompts defensive repetition, thereby perpetuating racist mind-sets and acts and taking one further and further from the possibility of reparation. On the other hand, the more normal interplay between persecutory and depressive guilt, which is illustrated through a clinical vignette, is seen as opening up a path to reparation. Brief vignettes are offered illustrating points about melancholic guilt and how a culture of facing rather than evading persecutory guilt enabled an opportunity for reparation to be recognized and used.
This article is a case study assessing transformation in one faculty of education at a South African university. This article explores aspects of transformation: equity, ideology, and practices. Of ...particular relevance is the experiences of Black academics in their struggle for social justice. Critical race theory is used as an analytical tool to make sense of the paradox of Black experiences of discrimination at the hands of Black faculty leadership and the concomitant entrenchment of Whiteness as dominant in the institutional culture. "Interest convergence" and institutionalized racism are plausible reasons for the racial paradox and reluctance of Black leadership to address discriminatory practices. To answer the research question, "What is the state of the transformation discourse in a merged faculty of education?" data were extracted from primary sources, reflective reports, and staff experiences. Findings point toward an underdeveloped, suppressed, and restrained transformation discourse based on outdated values and practices. Recommendations are made to embark on a "vigorous transformation indaba" to promote academic citizenship and social cohesion in the faculty.
Cutaneous melanoma represents the most lethal form of skin cancer and remains refractory to current therapies. Failure of treatment has been attributed to the over-expression of ABC transporters ...which efflux the drugs, below their cytotoxic threshold within cells. Therefore, this study set to investigate; the efficacy of a combinatorial approach comprising chemotherapy (Dacarbazine) and photodynamic therapy (PDT) to overcome resistance in pigmented and unpigmented metastatic melanoma and potentially identify resistant mechanisms.
The cytotoxic effect of the chemotherapy, PDT and combination therapy treatment (Dacarbazine+PDT) was determined using a cell viability XTT assay. Thereafter, melanoma cells morphology, self-renewal capacity and ABCG2 protein expression, were determined using fluorescence microscopy, clonogenic assay, western blot and flow cytometry. All results were analyzed by t-test and ANOVA, followed by individual comparisons with post-tests.
This study describes possible synergism of PDT+DTIC in reducing melanoma cell viability in vitro. At 24h post-treatment, only the unpigmented melanomas were sensitive to DTIC treatment (20–25% death at 1.25mM). At 48h, a lethal dose of 50% was reached in these cells in contrast to the pigmented melanoma (20% at 48h). The same trend was observed with the combination therapy (DTIC+PDT) at both time points. Furthermore, complete morphological disruption could be observed upon PDT only and PDT+DTIC treatments. Moreover, PDT and DTIC+PDT suppressed the self-renewal capacity of both melanoma cell lines. No significant differences in ABCG2 protein expression was found at 24h post-treatment.
Overall, these results suggest that human melanomas remain heterogeneous in their phenotypes. Moreover, in our metastatic melanoma cells, ABCG2 transporters did not seem to be involved in resistance to therapies. Significantly though, a combinatorial approach of PDT and chemotherapy significantly decreases the self-renewal capacity of metastatic melanoma cells and could be a suggested adjunctive approach to post-resection treatment regimes.
•Treatment of dacarbazine and PDT to overcome melanoma resistance, is proposed.•Synergism of dacarbazine and PDT exists in reducing melanoma cell viability.•Morphological disruption was observed upon PDT only and PDT+Dacarbazine treatments.•ABCG2 transporters contribute to decreasing the self-renewal capacity of melanoma.
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