Crystal sedimentation and stone formation

Mechanisms of crystal collision being the first step of aggregation (AGN) were analyzed for calcium oxalate monohydrate (COM) directly produced in urine. COM was produced by oxalate titration in urine of seven healthy men, in solutions of urinary macromolecules and in buffered distilled water (control). Crystal formation and sedimentation were followed by a spectrophotometer and analyzed by scanning electron microscopy. Viscosity of urine was measured at 37°C. From results, sedimentation rate (vS), particle diffusion (D) and incidences of collision of particles in suspension by sedimentation (IS) and by diffusion (ID) were calculated. Calculations were related to average volume and urinary transit time of renal collecting ducts (CD) and of renal pelvis. vS was in urine 0.026 ± 0.012, in UMS 0.022 ± 0.01 and in control 0.091 ± 0.02 cm min−1 (mean ± SD). For urine, a D of 9.53 ± 0.97 μm within 1 min can be calculated. At maximal crystal concentration, IS was only 0.12 and ID was 0.48 min−1 cm−3 which, even at an unrealistic permanent and maximal crystalluria, would only correspond to less than one crystal collision/week/CD, whereas to the same tubular wall being in horizontal position 1.3 crystals/min and to a renal stone 624 crystals/cm2 min could drop by sedimentation. Sedimentation to renal tubular or pelvic wall, where crystals can accumulate and meet with a tissue calcification or a stone, is probably essential for stone formation. Since vS mainly depends on particle size, reducing urinary supersaturation and crystal growth by dietary oxalate restriction seems to be an important measure to prevent aggregation

Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature

Backgroundoverexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome.Methodsin all, 168 T1-3, N0-1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy.Resultsin the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7, P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03) and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively.Interpretationthe 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies

The emergence and current performance of a health research system: lessons from Guinea Bissau

<p>Abstract</p> <p>Background</p> <p>Little is known about how health research systems (HRS) in low-income countries emerge and evolve over time, and how this process relates to their performance. Understanding how HRSs emerge is important for the development of well functioning National Health Research Systems (NHRS). The aim of this study was to assess how the HRS in Guinea Bissau has emerged and evolved over time and how the present system functions.</p> <p>Methods</p> <p>We used a qualitative case-study methodology to explore the emergence and current performance of the HRS, using the NHRS framework. We reviewed documents and carried out 39 in-depth interviews, ranging from health research to policy and practice stakeholders. Using an iterative approach, we undertook a thematic analysis of the data.</p> <p>Results</p> <p>The research practices in Guinea Bissau led to the emergence of a HRS with both local and international links and strong dependencies on international partners and donors. The post-colonial, volatile and resource-dependent context, changes in donor policies, training of local researchers and nature of the research findings influenced how the HRS evolved. Research priorities have mostly been set by 'expatriate' researchers and focused on understanding and reducing child mortality. Research funding is almost exclusively provided by foreign donors and international agencies. The training of Guinean researchers started in the mid-nineties and has since reinforced the links with the health system, broadened the research agenda and enhanced local use of research. While some studies have made an important contribution to global health, the use of research within Guinea Bissau has been constrained by the weak and donor dependent health system, volatile government, top-down policies of international agencies, and the controversial nature of some of the research findings.</p> <p>Conclusions</p> <p>In Guinea Bissau a de facto 'system' of research has emerged through research practices and co-evolving national and international research and development dynamics. If the aim of research is to contribute to local decision making, it is essential to modulate the emerged system by setting national research priorities, aligning funding, building national research capacity and linking research to decision making processes. Donors and international agencies can contribute to this process by coordinating their efforts and aligning to national priorities.</p

Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

BACKGROUND: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. OBJECTIVES: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. METHODS: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM(10) in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM(2.5) and PM(10) exposures over 2-years were estimated for each participant’s residential address using spatiotemporal interpolation in combination with a dispersion model. RESULTS: Average long-term PM(10) was 25.9 (± 5.4) and 23.7 (± 2.3) μg/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM(10) and the expression of individual genes differed by sex. In the validation cohort, long-term PM(10) was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM(10) in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM(10) exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women). CONCLUSIONS: Expression of the sex-specific candidate genes identified in the discovery population predicted PM(10) exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects. CITATION: Vrijens K, Winckelmans E, Tsamou M, Baeyens W, De Boever P, Jennen D, de Kok TM, Den Hond E, Lefebvre W, Plusquin M, Reynders H, Schoeters G, Van Larebeke N, Vanpoucke C, Kleinjans J, Nawrot TS. 2017. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women. Environ Health Perspect 125:660–669; http://dx.doi.org/10.1289/EHP37

Hereditary sensory neuropathy type I

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease

Clinical and genetic characterization of leukoencephalopathies in adults

Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults

Using Intervention Mapping to develop a programme to prevent sexually transmittable infections, including HIV, among heterosexual migrant men

<p>Abstract</p> <p>Background</p> <p>There is little experience with carefully developed interventions in the HIV/STI prevention field aimed at adult heterosexual target groups in the Netherlands. The ability to apply intervention development protocols, like Intervention Mapping, in daily practice outside of academia, is a matter of concern. An urgent need also exists for interventions aimed at the prevention of STI in migrant populations in the Netherlands. This article describes the theory and evidence based development of HIV/STI prevention interventions by the Municipal Public Health Service Rotterdam Area (MPHS), the Netherlands, for heterosexual migrant men with Surinamese, Dutch-Caribbean, Cape Verdean, Turkish and Moroccan backgrounds.</p> <p>Methods</p> <p>First a needs assessment was carried out. Then, a literature review was done, key figures were interviewed and seven group discussions were held. Subsequently, the results were translated into specific objectives ("change objectives") and used in intervention development for two subgroups: men with an Afro-Caribbean background and unmarried men with a Turkish and Moroccan background. A matrix of change objectives was made for each subgroup and suitable theoretical methods and practical strategies were selected. Culturally-tailored interventions were designed and were pre-tested among the target groups.</p> <p>Results</p> <p>This development process resulted in two interventions for specific subgroups that were appreciated by both the target groups and the migrant prevention workers. The project took place in collaboration with a university center, which provided an opportunity to get expert advice at every step of the Intervention Mapping process. At relevant points of the development process, migrant health educators and target group members provided advice and feedback on the draft intervention materials.</p> <p>Conclusion</p> <p>This intervention development project indicates that careful well-informed intervention development using Intervention Mapping is feasible in the daily practice of the MPHS, provided that sufficient time and expertise on this approach is available. Further research should test the effectiveness of these interventions.</p

A retrospective analysis of bilateral fractures over sixteen years: localisation and variation in treatment of second hip fractures

The aim of this study was the evaluation of contralateral hip fractures after a previous hip fracture. For this retrospective analysis patients were selected from the database of the LUMC, a teaching hospital in the south-west of the Netherlands. We analyzed all patients with a second fracture of a hip between 1992 and 2007. The exclusion criteria were high impact trauma and patients with diseases or medication known to have a negative effect on bone metabolism. A total of 1,604 hip fractures were identified. The possible predictive factors for the second fracture and descriptive statistics related to surgery (Hb and HT before and after the operation, total amount of intra- and postoperative blood loss, type of osteosynthesis, complications, time of death after the last fracture, time between arrival in the hospital and operation and hospital stay for both fractures) were recorded. A total of 32 second hip fractures were identified (2%) at a mean of 27.5 (SD 28.9) months after the initial hip fracture. The mean age at the first fracture was 77.2 years (SD 11.7), and 27 of 32 patients were female. Of these 32 patients (64 bilateral hip fractures), 32 fractures were intracapsular (1 femoral neck, 31 subcapital) and 32 were extracapsular fractures (6 subtrochanteric, 26 transtrochanteric). Although 24 of the 32 patients had identical first and second hip fractures, only eight out of 32 hips were treated with the same implants. There was a significant difference in Singh index between both hips at the time of the first fracture. There was also a significant difference in Singh index between the hip which was not fractured compared with its subsequent index when it was broken. All other studied patient and fracture characteristics were not significantly different. In this population the percentage of second hip fractures was relatively low compared to other studies. The choice of implants in this study shows that implants were chosen randomly. Because there is a significant difference in the Singh index during first and second hip fracture, osteoporosis medication might help reduce the incidence of second hip fractures