NGN2-based neuronal programming of hiPSCs in an automated microfluidic platform.

The generation of induced pluripotent stem cells (iPSCs) via somatic cell reprogramming allowed to have an unlimited in vitro source of patient-specific cells. This achievement has introduced a new revolutionary way to create human in vitro models and to study human diseases starting from patient's own cells, especially important for inaccessible tissues like the brain. Recently, lab-on-a-chip technology has opened new reliable alternatives to conventional in vitro models able to replicate key aspects of human physiology, thanks to the intrinsic high surface-area-to-volume ratio, which allows fine control of the cellular microenvironment. The development of automated microfluidic platforms allowed the implementation of this technology to perform high-throughput, standardized and parallelized assays, suitable for drug screenings and developing new therapeutic approaches in a cost-effective way. However, the major challenges in the broad application of automated lab-on-a-chip in biological research are the lack of production robustness and ease of use of the devices. Here, we present an automated microfluidic platform able to host the rapid conversion of human iPSCs (hiPSCs) into neurons via viral-mediated overexpression of Neurogenin 2 (NGN2) in a user-friendly manner. The design of the platform, built with multilayer soft-lithography techniques, shows easiness in the fabrication and assembly thanks to the simple geometry and experimental reproducibility at the same time. All operations are managed automatically, from the cell seeding, medium change, doxycycline-mediated neuronal induction, selection of the genetically engineered cells, and analysis of the output of differentiation, including immunofluorescence assay. Our results show a high-throughput, efficient and homogenous conversion of hiPSCs into neurons in 10 days, characterized by the expression of the mature neuronal marker MAP2 and calcium signaling. The neurons-on-chip model here described represents a fully automated loop system able to address the challenges in the field of neurological diseases modelling in vitro and improve current preclinical models.

Fracture of the cobalt-chromium modular femoral neck component in total hip arthroplasty.

Total hip prostheses using cervico-metaphyseal modularity were designed to better replicate the geometry of the native extra-medullary femur. However, they are associated with numerous complications including corrosion, disassembly, pseudotumours and, most notably, fractures of the modular neck. All reported cases of modular neck fractures occurred with titanium components (Ti-6Al-4V). To prevent this weakness, manufacturers developed modular necks made of cobalt-chromium (Co-Cr). We report a fracture of a long, 8° varus, Co-Cr modular neck connected to a 36-mm short (-3.5mm) femoral head. The fracture occurred 22 months post-implantation in a woman who had a low level of physical activity and a body mass index of 28.7 kg/m(2). To our knowledge, this case is the first reported instance of Co-Cr modular neck fracture. It may challenge the wisdom of further developing this modularity design, as our patient had none of the known risk factors for modular neck fracture. In addition, cases of pseudotumour have been reported with Co-Cr modular necks subjected to fretting corrosion, which contributed to the fracture in our patient.

Subtypes of depression in dementia.

Depression is one of the most frequent neuropsychiatric comorbidities of Alzheimer dementia (AD), affecting patents with rates from 0% to 87%. These rates vary because different populations are sampled and different instruments are used. Depressive symptoms tend to occur early, are persistent, becoming increasingly common as dementia progresses. Depression decreases the quality of life of dementia sufferers, may reduce the duration of survival and would therefore appear to be important to treat. Although questions about the interrelationships between depression and dementia have been central to the field of geriatric psychiatry for the past 30 to 40 years, clinical approaches continue to evolve through a categorical or dimensional approach.

Beyond nosography of depression in elderly.

The patterns of depressive symptoms that occur in the elderly are appreciably different from those manifested in younger-age groups. Older depressed patents tend to report more somatic and cognitive symptoms than affective ones. An exclusively categorical approach to depression among the elderly does not provide adequate means for an exhaustive classification of mood disorders in old age. Taking into account clinical features, high comorbidity and the overlap with the physiological somatic changes due to aging, a dimensional approach seems to better account for depressive symptoms in the elderly.

A randomised comparison of the use of 4 and 6 French diagnostic catheters: the limits of downsizing.

BACKGROUND: The use of small catheters for coronary angiography can reduce the risk of vascular complications and allow early ambulation, but excessive downsizing may lead to poor quality imaging. The aim of this study was to assess the feasibility of performing coronary angiography using 4 French (4 F) femoral catheters. METHODS: In total, 400 consecutive elective patients were randomised to undergo coronary angiography with 4 F or 6 F catheters. The puncture site was manually compressed and inspected before and after ambulation, and 24 h later. The handling difficulty of the catheters was semi-quantitatively evaluated using a three grade scoring system; angiogram quality was evaluated by two independent physicians. RESULTS: No major procedure-related complications were observed. Coronary arteriography with 4 F catheters was possible in all of the attempted cases. There were no statistical differences between the two groups in terms of procedural or fluoroscopy time, the amount of contrast medium used, or the incidence of vascular complications, while compression time was significantly shorter in the patients studied using the smaller catheter (3.4 vs. 9.9 min; P<0.0001). Catheter stability was similar in the two groups, whereas catheter torque and the quality of the coronary angiograms were statistically better in the patients studied using six French catheters. CONCLUSIONS: Coronary angiography with 4 F catheters is technically feasible and permits early ambulation after the procedure. Although the radiological resolution of the images obtained using 4 F catheters was always adequate for clinical decision-making, the angiogram quality and catheter handling were significantly better using the 6 F system.

Noninvasive assessment of cardiac risk in type I diabetic patients being evaluated for combined pancreas-kidney transplantation using dipyridamole-MIBI perfusion tomographic scintigraphy.

This study was performed to determine the value of dipyridamole-99m Tc-methoxy-isobutyl isonitrile perfusion (99mTC-MIBI) tomographic scintigraphy in the assessment of cardiac risk in patients being evaluated prior to combined pancreas-kidney transplantation (PKT). We performed perfusion tomographic scintigraphy using single photon emission computed tomography (SPECT) on 77 patients. The tomographic images did not show clinically relevant findings in 65 patients. In the remaining 12 patients, coronary arteriography was performed: 2 showed normal results, 4 showed no stenosis, and 6 showed significant stenosis ( > or = 70%). Seventy-two patients underwent PKT. During the follow-up (6-48 months), there were seven cardiac events, 4 patients with significant stenosis, and 3 with nonsignificant stenosis upon coronary arteriography, and all had pathological tomographic images. 99mTc-MIBI tomographic scintigraphy may be useful in identifying patients at low risk of incurring cardiac events after PKT and may, in a large group of patients, obviate the need for routine coronary angiography.

Indium-111 labelled platelet scintigraphy can predict the immunological origin of fever in patients on dialysis carrying a non-functioning renal allograft.

The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft. We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6+/-12 years). The mean duration of PFS was 35 days (range 7-122). Forty-six of the 91 patients underwent steroid therapy (2-10 mg/day). Platelet labelling was carried out following Thakur's method. Platelet scans were performed 48 h after reinjection of labelled platelets. The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI. The final diagnosis of PFS was established depending on the outcome after treatment. In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy. In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin). The PUI in patients with immunological PFS was 1.80+/-0.7, while in patients with non-immunological PFS it was 1.12+/-0.1 (P<0.05). When a PUI of > or =1.5 was considered as the threshold to establish PFS of immunological origin, the sensitivity of platelet scan was 76%, the specificity 100%, and the negative and positive predictive values 69% and 100%, respectively. In patients classified with immunological PFS who underwent steroid therapy, the PUI was significantly lower than in patients without steroids (P<0.05). These results suggest that 111In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft. Therapy with steroids could reduce the sensitivity of 111In-labelled platelet scintigraphy in detecting immunological PFS.

Brain perfusion and neuropsychological changes in schizophrenic patients after cognitive rehabilitation.

The role of cognitive variables was compared in two single cases of schizophrenia hypofrontality. SPECT procedures and neuropsychological tests were used to study frontal brain function. After cognitive rehabilitation, neuropsychological performance were enhanced in both patients, but only one of them showed enhanced the frontal blood flow. The brain perfusion changes after cognitive rehabilitation could be associated with the cognitive-dependent hypofrontality.

[Use of bone SPECT of the dorsolumbar spine in oncological patients with suspected bone metastases]. / Utilidad del SPECT óseo de columna dorsolumbar en pacientes oncológicos con sospecha de metástasis óseas.

UNLABELLED: A retrospective study was made to evaluate the usefulness of bone SPECT of the dorsolumbar spine in identifying benign and malignant lesions. A study was made of oncological patients who presented active images in the spinal column visible on planar radionuclide scans who also underwent SPECT. The average follow-up period was 25+/-13 months. MATERIAL AND METHOD: In 43 neoplastic patients 55 visible lesions on SPECT were evaluated, of which 29 were benign and 26 metastatic. The criteria for benign lesions were the absence of change or involution without treatment in the follow-up period. The criteria for classifying metastases were: 1. Positive biopsy. 2. Neurological complications derived from the lesion. 3. Increased extension and tracer uptake by the lesion, and the appearance of other bone metastases. RESULTS: Twelve of 15 lesions located in the vertebral body or pedicle and 11/16 located in the body with extension toward the pedicles were metastases. Twenty-one of 24 lesions located on the anterior face of the vertebral body, articular processes, lamina, or intervertebral disk were benign. CONCLUSION: Bone SPECT was useful for locating the vertebral lesion, which in many cases allows differentiation of benign and metastatic lesions.

[Nutrition integrators in sports]. / Gli integratori alimentari nello sport.

The use or abuse of many preparations, available in the gymnasium or as top-bench drugs, used as nutritive integrators, determines both toxicological and deontological and especially sport medicine problems, because these products are also involved in the antidoping control. Therefore, this article cover the needs for providing a consultation and information manual for all sport operators in the delicate phase of drug-food integration of the athlete, not only to prevent and restrict the doping phenomenon, but also for health-preservation of the athlete.

[Transient enterotoxemia following tooth extraction: observations on the Limulus test]. / Transitoria endotossiemia dopo avulsioni dentarie: osservazioni col Limulus test.

The incidence of endotoxemia (with limulus assay) in a group of patients undergoing dental extraction of both normal and diseased teeth was determined. Transient endotoxemia was found in 7 caes, without incidence of bacteremia.