Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.

Towards remote healthcare monitoring using accessible IoT technology: state-of-the-art, insights and experimental design.

Healthcare studies are moving toward individualised measurement. There is need to move beyond supervised assessments in the laboratory/clinic. Longitudinal free-living assessment can provide a wealth of information on patient pathology and habitual behaviour, but cost and complexity of equipment have typically been a barrier. Lack of supervised conditions within free-living assessment means there is need to augment these studies with environmental analysis to provide context to individual measurements. This paper reviews low-cost and accessible Internet of Things (IoT) technologies with the aim of informing biomedical engineers of possibilities, workflows and limitations they present. In doing so, we evidence their use within healthcare research through literature and experimentation. As hardware becomes more affordable and feature rich, the cost of data magnifies. This can be limiting for biomedical engineers exploring low-cost solutions as data costs can make IoT approaches unscalable. IoT technologies can be exploited by biomedical engineers, but more research is needed before these technologies can become commonplace for clinicians and healthcare practitioners. It is hoped that the insights provided by this paper will better equip biomedical engineers to lead and monitor multi-disciplinary research investigations.

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..

Lessons to be learned: a case study approach insulinoma presenting as a change in personality.

A 43-year-old man presented with attacks of altered behaviour over a short period of time; they were associated with episodes of hypoglycaemia. The clinical suspicion of insulinoma prompted investigations that quickly established serum insulin and C-peptide levels to be elevated at the times when blood glucose values were low. A physical lesion was found in the head of the pancreas by means of computerised tomography and endo-duodenal ultrasound scan; an octreotide scan was negative. The patient underwent laparotomy and enucleation of a benign tumour, measuring 2.6 cm in diameter, lying within the head of the pancreas; histological examination confirmed it to be an insulinoma. Postoperatively, the patient's personality gradually became more normal and his fasting blood glucose concentrations returned to within normal limits. The diagnosis and management of insulinoma are discussed in the context of this clinical case; there is also reference to the protean clinical manifestations that may occur in this condition- and its differential diagnosis.

The Harm Reduction Coalition.

AIDS: The Harm Reduction Coalition (HRC) is a national organization committed to reducing drug-related harm among individuals and communities through education, intervention, and community organization. HRC is working towards changing national drug policies to a harm reduction approach, organizing information sharing, developing resources, and lifting the Federal ban on needle exchange programs. HRC tries to help users make safer choices regarding drug use behavior and sexual behavior. The Coalition also works with other organizations to help them model programs based on harm reduction principles, using the Harm Reduction Training Institute, and they are working on expanding syringe access throughout the United States by changing Federal and local policies.^ieng

Mammographically detected breast cancer: location in women under 50 years old.

The mammograms of 86 women under the age of 50 years with mammographically detected cancers were reviewed. Sixty-three of these cancers (73%) were found at the periphery of the breast as defined by a zone 1 cm wide beneath the subcutaneous fat or anterior to the retromammary fat. This finding is likely due to the geometric configuration of the breast. If the breast is hemispheric, then more than 50% of the volume of breast tissue lies within this zone in a large percentage of women. Furthermore, the contrasting adjacent fat likely improves the ability to perceive an abnormality. Interaction of the terminal ducts with chemicals contained within or produced by the fat is a much less likely reason for the high percentage of cancers in this zone. Radiologists should be aware of this phenomenon and pay particular attention to this zone.

Breast cancer survival among women under age 50: is mammography detrimental?

Great uncertainty exists about the benefit of detecting breast cancer by mammography in women under 50 years of age. We have reviewed the survival of patients aged 49 years or less whose cancers were detected by mammography alone. 117 women under the age of 50 years were diagnosed with breast cancer between 1978 and 1991 based only on an abnormal mammogram. Ductal carcinoma in-situ (DCIS) was found in 47 (40%) of these women, whilst 70 (60%) had infiltrating ductal or infiltrating lobular carcinomas. During the same interval, 928 women in this age group presented with palpable breast cancer. DCIS was diagnosed in 82 (9%) of these women, whilst 846 (91%) had infiltrating carcinoma. Among the infiltrating cancers detected by mammography alone, 50% were stage I, whilst only 30% of the women with palpable cancers were stage I. Five-year survival for all mammographically detected cancer patients was 95%, whereas for women with palpable cancers the survival was 74% (p < 0.00005). If DCIS is not included, the corresponding survivals are 91% for mammographically detected infiltrating cancers and 72% for palpable infiltrating cancers. Only 1 woman who died among those with palpable cancer had had a mammogram before diagnosis. Our data contradict the suggestion that women under 50 are put at a survival disadvantage by undergoing mammography. We believe that investigators who have reported negative results in this age group must examine other causes for their results.

Calcified suture material in the breast after radiation therapy.

Of 335 women who underwent lumpectomy and radiation therapy for breast cancer, 42 subsequently developed calcifications. Particles typical of calcified suture material were identified in 21 of the 42 women (50%). No obvious calcified suture material was found in approximately 1,140 women of 38,000 (3%) who had undergone mammography after they had previously undergone breast biopsy for a benign lesion and thus had not undergone radiation therapy. Calcified suture material rarely develops in the nonirradiated breast, but it is common after radiation therapy and should not be confused with recurrent breast cancer. These calcifications are likely the result of delayed resorption of catgut sutures, which provide a matrix on which calcium can precipitate in a suitable local environment.

Chest wall reconstruction after resection of recurrent breast tumours.

A series of 13 chest wall resections for recurrent breast tumours are reported, the defects being closed by synthetic prostheses. In nine patients the prostheses were covered by a latissimus dorsi flap, while in the last eight patients a rigid 'shield' prosthesis of methyl methacrylate was used, and a stable chest obtained. Mechanical ventilation for more than 24 h was not required in those patients in whom a shield was used.

Effects of isosorbide dinitrate on the pattern of arterial blood flow in healthy human subjects.

1. Blood velocity measurements have been made in the superficial femoral artery, 10 cm downstream of the common femoral artery bifurcation, in healthy human subjects, using a multi-channel Doppler ultrasound device. 2. In a randomized double-blind protocol, the effects of isosorbide dinitrate were examined during a 2 h period. 3. The changes induced by isosorbide dinitrate include: (i) an increase in the width of the artery and a reduction in brachial arterial blood pressure, implying relaxation of arterial smooth muscle; (ii) an increase in reverse flow and a decrease in time-averaged mean velocity associated with a relatively small decrease of the velocity excursion during the cardiac cycle, implying an increase in flow pulsatility; and (iii) an alteration of the flow pattern both in the core and near the vessel walls.

Sialography does not alter the management of parotid space-occupying lesions.

The value of sialography in unilateral space-occupying lesions of the parotid gland has been reviewed. The investigation caused discomfort and did not alter the clinical diagnosis or management of the patients examined.

Unusual presentation of patients with myelomatosis in Malawi.

Malignant myeloma is not rare in tropical Africa. Its mode of presentation in Malawi is most often that of a tumour mass in bone. The types of immunoglobulin heavy and light chains in the tumour cells occur with a frequency similar to that observed in temperate countries.

Unusual presentation of patients with myelomatosis in Malawi

Malignant myeloma is not rare in tropical Africa. Its mode of presentation in Malawi is most often that of a tumour mass in bone. The types of immunoglobulin heavy and light chains in the tumour cells occur with a frequency similar to that observed in temperate countries