Tumour‐associated mast cells in classical Hodgkin's lymphoma: correlation with histological subtype,other tumour‐infiltrating inflammatory cell subsets and outcome

The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed–Sternberg cells within a heterogeneous background of non‐neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour‐infiltrating mast cells in cHL tissue microarrays and correlated this with clinico‐pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event‐free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.     

Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana: a factor of potential importance for auxin-cytokinin-regulated development

One of the most long-lived models in plant science is the belief that the long-distance transport and ratio of two plant hormones, auxin and cytokinin, at the site of action control major developmental events such as apical dominance. We have used in vivo deuterium labeling and mass spectrometry to investigate the dynamics of homeostatic cross talk between the two plant hormones. Interestingly, auxin mediates a very rapid negative control of the cytokinin pool by mainly suppressing the biosynthesis via the isopentenyladenosine-5'-monophosphate-independent pathway. In contrast, the effect of cytokinin overproduction on the entire auxin pool in the plant was slower, indicating that this most likely is mediated through altered development. In addition, we were able to confirm that the lateral root meristems are likely to be the main sites of isopentenyladenosine-5'-monophosphate-dependent cytokinin synthesis, and that the aerial tissue of the plant surprisingly also was a significant source of cytokinin biosynthesis. Our demonstration of shoot-localized synthesis, together with data demonstrating that auxin imposes a very rapid regulation of cytokinin biosynthesis, illustrates that the two hormones can interact also on the metabolic level in controlling plant development, and that the aerial part of the plant has the capacity to synthesize its own cytokinin independent of long-range transport from the root system.     

Social relations as determinant of onset of disability in aging

The purpose of the study was to analyze whether social relations are related to onset of disability among old people at 1.5 year follow-up and whether these relations vary by age and gender. The study is based on baseline and 1.5 year follow-up data on 1396 older non-disabled adults. Social relations were measured by questions about diversity in social relations, social participation, satisfaction with social relations and instrumental social support. Onset of disability was described as developing need of help in at least one of six mobility activities. The results showed that a large diversity in social relations and high social participation were important factors for maintaining functional ability among the 75-year-old men and women, while social support was a risk factor for functional decline among the 80-year-old men. The present study suggests that being "embedded" in a strong network of social relations provides protection against disability by reducing risk of developing disability.     

Generation of urinary albumin fragments does not require proximal tubular uptake

Urinary albumin excretion is an important diagnostic and prognostic marker of renal function. Both animal and human urine contain large amounts of albumin fragments, but whether these fragments originate from renal tubular degradation of filtered albumin is unknown. Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular endocytosis of albumin, to determine whether proximal tubular degradation of albumin forms the detectable urinary albumin fragments. After intravenous administration of (125)I-labeled mouse albumin to knockout and control mice, we examined kidney uptake of albumin and urinary excretion of both intact albumin and its fragments using size exclusion chromatography. In control mice, all labeled albumin eluted as albumin fragments in the urine. In megalin/cubilin-deficient mice, we observed decreased uptake and degradation of albumin and increased urinary excretion of intact albumin; we did not, however, detect a decrease in the excretion of albumin fragments. These results show that the generation of urinary albumin fragments occurs independently of renal tubular uptake and degradation of albumin, suggesting that the pathophysiological implications of changes in urinary albumin fragments require reevaluation.     

CT of the paranasal sinuses is not a valid indicator for sinus surgery in CF patients

BackgroundNo guidelines comprise when or to what extent sinus surgery should be done in patients with cystic fibrosis (CF) or how a CT scan of the paranasal sinuses should influence the decision. Symptoms of rhinosinusitis and/or eradication of pathogenic bacteria from the sinuses are reasons for sinus surgery.MethodsIn this observational cross sectional study, 55 CF cases had their preoperative CT scans scored according to the Lund Mackay- and the Nair-system. Correlations between the CT scans, symptoms, surgical findings and cultures obtained during sinus surgery were made.ResultsThere was no significant correlation between the CT score and detection of pus, pathogenic bacteria or symptoms. Pus and pathogenic bacteria were found in several cases without sinus opacification on the CT scan. Non pathogenic and sterile cultures were also found in sinuses with opacification.ConclusionsA CT scan is not a valid criterion for sinus surgery in CF patients.     

The Effect of Early Initiation of Rehabilitation After Lumbar Spinal Fusion: A Randomized Clinical Study

STUDY DESIGN.: A multicenter randomized clinical trial including 82 patients. OBJECTIVE.: To examine the effect of early initiation of rehabilitation after instrumented lumbar spinal fusion. SUMMARY OF BACKGROUND DATA.: Lumbar spinal fusion has been performed for more than 70 years. Yet, few studies have examined patients' subsequent rehabilitation. Group-based rehabilitation is both efficient and cost-effective in rehabilitation of lumbar spinal fusion patients. METHODS.: Patients with degenerative disc diseases undergoing instrumented lumbar spinal fusion were randomly assigned to initiate their rehabilitation 6 weeks (6-wk group) or 12 weeks after lumbar spinal fusion (12-wk group). Both groups received the same group-based rehabilitation. Primary outcome was the Oswestry Disability Index. Secondary outcome was the Dallas Pain Questionnaire, the Low Back Pain Rating Scale, and absence from work. Wilcoxon rank-sum test was used to compare the groups in terms of differences from baseline to 6 months and 1-year follow-up. Results are presented in median with 25th and 75th percentiles. RESULTS.: According to the Oswestry Disability Index, at 1-year follow-up, the 6-week-group had a median reduction of -6 (-19; 4) compared with -20 (-30;-7) in the 12-week group (P, 0.05). The Dallas Pain Questionnaire showed overall the same tendency, and within daily activities were significantly reduced in favor of the 12-week group (P, 0.05). For back pain, the 6-week group had a median reduction of -2.2 (-3.0; -0.7) similar with -3.3 (-4.7; -1.7) in the 12-week group (P, 0.05). The results at 6 months of follow-up were similar. No difference was found according to return to work 1 year postsurgery. CONCLUSION.: Early start of rehabilitation (6 wk vs. 12 wk) after lumbar spinal fusion resulted in inferior outcomes. The improvements in the 12-week group were 4 times better than that in the 6-week group, indicating that the start-up time of rehabilitation is an important contributing factor for the overall outcome.     

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes,risk factors and genotypes

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0–17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31–10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10^-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.     

Short-term exposure to stone minerals used in asphalt affect lung function and promote pulmonary inflammation among healthy adults

ObjectiveStone minerals are a partially ignored environmental challenge but a significant contributor to urban air pollution. We examined if short-term exposure to two stone minerals – quartz diorite and rhomb porphyry – commonly used in asphalt pavement would affect lung function, promote pulmonary inflammation, and affect bronchial reactivity differently.MethodsOur randomized crossover study included 24 healthy, non-smoking young adults exposed to the stone minerals quartz diorite, rhomb porphyry, and control dust (lactose). Exposure occurred in an exposure chamber, in three separate 4-hour exposure sessions. Fractional exhaled nitric oxide (FeNO) and lung function were monitored before exposure, then immediately following exposure, and 4 and 24 hours after exposure. In addition, methacholine was administered 4 hours following exposure, and exhaled breath condensate (EBC) was collected before exposure, then immediately and 4 hours after exposure. EBC was analyzed for pH, thiobarbituric acid reactive substances (TBARS), intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), IL-10, P-Selectin, surfactant protein D (SP-D), and tumor necrosis factor-α (TNF-α).ResultsOur results showed significantly elevated concentrations of FeNO after exposure to quartz diorite compared to rhomb porphyry, suggesting that quartz diorite is more likely to trigger pulmonary inflammation after short-term exposure. Moreover, short-term exposure to rhomb porphyry was associated with a modest but statistically significant decline in forced vital capacity (FVC) compared to quartz diorite.ConclusionThese results emphasize that using stone material in asphalt road construction should be reconsidered as it may affect lung inflammation and lung function in exposed subjects.