Co-axial printing of convoluted proximal tubule for kidney disease modeling.

Despite the increasing incidence of kidney-related diseases, we are still far from understanding the underlying mechanisms of these diseases and their progression. This lack of understanding is partly because of a poor replication of the diseasesin vitro,limited to planar culture. Advancing towards three-dimensional models, hereby we propose coaxial printing to obtain microfibers containing a helical hollow microchannel. These recapitulate the architecture of the proximal tubule (PT), an important nephron segment often affected in kidney disorders. A stable gelatin/alginate-based ink was formulated to allow printability while maintaining structural properties. Fine-tuning of the composition, printing temperature and extrusion rate allowed for optimal ink viscosity that led to coiling of the microfiber's inner channel. The printed microfibers exhibited prolonged structural stability (42 days) and cytocompatibility in culture. Healthy conditionally immortalized PT epithelial cells and a knockout cell model for cystinosis (CTNS-/-) were seeded to mimic two genotypes of PT. Upon culturing for 14 days, engineered PT showed homogenous cytoskeleton organization as indicated by staining for filamentous actin, barrier-formation and polarization with apical markerα-tubulin and basolateral marker Na+/K+-ATPase. Cell viability was slightly decreased upon prolonged culturing for 14 days, which was more pronounced inCTNS-/-microfibers. Finally,CTNS-/-cells showed reduced apical transport activity in the microfibers compared to healthy PT epithelial cells when looking at breast cancer resistance protein and multidrug resistance-associated protein 4. Engineered PT incorporated in a custom-designed microfluidic chip allowed to assess leak-tightness of the epithelium, which appeared less tight inCTNS-/-PT compared to healthy PT, in agreement with itsin vivophenotype. While we are still on the verge of patient-oriented medicine, this system holds great promise for further research in establishing advancedin vitrodisease models.

Compact X-Band Electron Linac for Radiotherapy and Security Applications.

RadiaBeam has developed a 6 MeV accelerator that is compact and light enough to be placed on a robotic arm or light truck. The main drivers of size and weight in conventional accelerators are the power source and the shielding. Small dimensions are enabled by operation at 9.3 GHz frequency (X-band), which allows reducing the size and weight of all accelerator components. Thanks to the robust design of the accelerating structure, the accelerator can be used as a source for novel cargo inspection and radiotherapy techniques. In this paper, we present the linac design and its components, as well the results of the experimental demonstration of beam acceleration.

A Practical Approach to the Diagnosis and Treatment of Adult Erythroderma. / Eritrodermia en el adulto: un enfoque práctico para el diagnóstico y tratamiento.

Erythroderma is an inflammatory skin syndrome that involves desquamation and erythema of more than 90% of the body surface area. It represents a final clinical endpoint for many adult dermatological conditions. The most frequent cause of erythroderma is psoriasis followed by eczematous conditions, drug-induced reactions, pityriasis rubra pilaris and cutaneous T-cell lymphomas. Diagnostic approach must include a thorough history and clinical examination. If the etiology of erythroderma is uncertain multiple skin biopsies may enhance diagnostic accuracy. The initial management of erythroderma must include a nutrition expert evaluation, fluid imbalance assessment, maintaining skin barrier function, sedative antihistamines and exclusion of secondary bacterial infection. We present a practical review of the etiology, diagnosis, and treatment of this entity.

von Willebrand's disease in Mexico: a pilot study.

von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder. For a long time, it has been said that VWD was absent in some countries due to ethnical differences. Information about the prevalence of VWD in Mexico remains unclear, owing largely to poor awareness and diagnosis of the disease. The aim of this study was to objectively diagnose VWD in a cohort of highly selected Mexican patients with a chronic history of bleeding. Mexican Mestizos were recruited between July 2010 and August 2011. Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for female patients was 19.5 years (range 3-44 years) and 18.5 years (range 4-63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1-61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty-six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and plasma concentrates.

Demonstration of a real-time interferometer as a bunch-length monitor in a high-current electron beam accelerator.

A real-time interferometer (RTI) has been developed to monitor the bunch length of an electron beam in an accelerator. The RTI employs spatial autocorrelation, reflective optics, and a fast response pyro-detector array to obtain a real-time autocorrelation trace of the coherent radiation from an electron beam thus providing the possibility of online bunch-length diagnostics. A complete RTI system has been commissioned at the A0 photoinjector facility to measure sub-mm bunches at 13 MeV. Bunch length variation (FWHM) between 0.8 ps (~0.24 mm) and 1.5 ps (~0.45 mm) has been measured and compared with a Martin-Puplett interferometer and a streak camera. The comparisons show that RTI is a viable, complementary bunch length diagnostic for sub-mm electron bunches.

Therapeutic evaluation of UVB-targeted phototherapy in vitiligo that affects less than 10% of the body surface area.

BACKGROUND: Current treatments for vitiligo include different therapeutic modalities, such as corticosteroids, immunomodulators, pseudocatalase, skin grafts, diverse types of phototherapy [ultraviolet B (UVB), psoralen plus UVA (PUVA), narrow-band UVB (NB-UVB)], and, recently, targeted phototherapy. After a literature search, we found only two studies using different targeted broad-band UVB units for the treatment of vitiligo. OBJECTIVE: To evaluate the repigmentation response induced with broad-band, UVB-targeted phototherapy used as monotherapy in patients with vitiligo affecting less than 10% of the skin surface. METHODS: Twelve patients were recruited for treatment with 30 sessions of UVB-targeted phototherapy administered twice weekly. The assessment of repigmentation was made from a comparison of baseline photographs with those after 30 sessions by two independent investigators. Morphometric analysis was performed using a computer program. RESULTS: Repigmentation with an average of 66.25% was obtained on lesions of the face, and of 31.5% on the neck, trunk, and genitalia. On the extremities, there was no repigmentation. Itching, a burning sensation, erythema, desquamation, and transitory hyperpigmentation were observed in some patients. Minimal blistering and ulceration were observed in one patient. CONCLUSION: Targeted UVB phototherapy seems to be effective for the repigmentation of vitiligo in lesions located on the face, to a lesser degree on the trunk, and with no response in acral lesions; there were minimal adverse effects that did not require discontinuation of treatment.

In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) has been recognized as a hematologic neoplasia that originates at the level of a primitive lymphoid stem/progenitor cell. To date, however, the biology of the hematopoietic system in this disorder is still not fully understood. In the present study, we have determined the progenitor cell content (including myeloid, erythroid and multipotent progenitors) in 14 children with ALL and followed the proliferation kinetics of these cells in Dexter-type long-term marrow cultures. We have also characterized some aspects related to the composition and function of the hematopoietic microenvironment developed in vitro. All patients included in this study showed extremely reduced levels of progenitor cells (median of 6.2% of the levels found in normal marrow). Proliferation of these cells in long-term cultures was markedly deficient, since they showed very low numbers - compared to normal cultures - and reached undetectable levels after only a few weeks. Regarding the microenvironment developed in vitro, whereas normal marrow samples contained a median of 8 fibroblastic progenitors/10(5) marrow cells and the stromal cell layers developed in culture contained a median of 341000 adherent cells per well, ALL marrow samples showed no fibroblastic progenitors and the numbers of adherent cells were 21% of those in normal cultures. Interestingly, the levels of TNFalpha and IL-6 in ALL culture supernatants were significantly increased, compared to normal cultures. Bone marrow samples from all 14 children were also analyzed once they reached a complete clinical and hematological remission. Myeloid, erythroid and multipotent progenitor cell levels were significantly increased, compared to patients at diagnosis, and proliferation of myeloid progenitors in long-term cultures was also improved. In contrast, proliferation of erythroid progenitors showed no difference to that in cultures from patients at diagnosis. The numbers of fibroblastic progenitors and adherent cells were significantly increased, compared to patients at diagnosis, and TNFalpha and IL-6 levels returned to normal. In summary, in the present study, we have demonstrated significant in vitro alterations of the hematopoietic system, both in terms of its composition and function, in pediatric patients with ALL. Importantly, most of these alterations are corrected, at least partially, after chemotherapy.