A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Hypercalcemia after transplant nephrectomy in a hemodialysis patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hypercalcemia is a complication often seen in chronic hemodialysis patients. A rare cause of this condition is sarcoidosis. Its highly variable clinical presentation is challenging. Especially in patients suffering chronic kidney graft failure the nonspecific constitutional symptoms of sarcoidosis like fever, weight loss, arthralgia and fatigue may be easily misleading.</p> <p>Case presentation</p> <p>A 51 year old male developed hypercalcemia, arthralgia and B-symptoms after explantation of his kidney graft because of suspected acute rejection. The removed kidney showed vasculopathy and tubulointerstitial nephritis, which had not been overt in the biopsy taken half a year earlier. Despite explantation and withdrawal of the immunosuppression the patient's general condition deteriorated progressively. A rapid rise in serum calcium finally provoked us to check for sarcoidosis. CT scans of the lungs, broncho-alveolar-lavage and further lab tests confirmed the diagnosis.</p> <p>Conclusion</p> <p>This case demonstrates that withdrawal of immunosuppressive drugs sometimes unmasks sarcoidosis. It should be considered as differential diagnosis even in hemodialysis patients, in whom other reasons for hypercalcemia are much more common.</p

Fishing the Molecular Bases of Treacher Collins Syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Soft network composite materials with deterministic and bio-inspired designs

Hard and soft structural composites found in biology provide inspiration for the design of advanced synthetic materials. Many examples of bio-inspired hard materials can be found in the literature; far less attention has been devoted to soft systems. Here we introduce deterministic routes to low-modulus thin film materials with stress/strain responses that can be tailored precisely to match the non-linear properties of biological tissues, with application opportunities that range from soft biomedical devices to constructs for tissue engineering. The approach combines a low-modulus matrix with an open, stretchable network as a structural reinforcement that can yield classes of composites with a wide range of desired mechanical responses, including anisotropic, spatially heterogeneous, hierarchical and self-similar designs. Demonstrative application examples in thin, skin-mounted electrophysiological sensors with mechanics precisely matched to the human epidermis and in soft, hydrogel-based vehicles for triggered drug release suggest their broad potential uses in biomedical devices. &amp;#169; 2015 Macmillan Publishers Limited. All rights reservedopen7

Biomechanical effects of polyaxial pedicle screw fixation on the lumbosacral segments with an anterior interbody cage support

BACKGROUND: Lumbosacral fusion is a relatively common procedure that is used in the management of an unstable spine. The anterior interbody cage has been involved to enhance the stability of a pedicle screw construct used at the lumbosacral junction. Biomechanical differences between polyaxial and monoaxial pedicle screws linked with various rod contours were investigated to analyze the respective effects on overall construct stiffness, cage strain, rod strain, and contact ratios at the vertebra-cage junction. METHODS: A synthetic model composed of two ultrahigh molecular weight polyethylene blocks was used with four titanium pedicle screws (two in each block) and two rods fixation to build the spinal construct along with an anterior interbody cage support. For each pair of the construct fixed with polyaxial or monoaxial screws, the linked rods were set at four configurations to simulate 0°, 7°, 14°, and 21° lordosis on the sagittal plane, and a compressive load of 300 N was applied. Strain gauges were attached to the posterior surface of the cage and to the central area of the left connecting rod. Also, the contact area between the block and the cage was measured using prescale Fuji super low pressure film for compression, flexion, lateral bending and torsion tests. RESULTS: Our main findings in the experiments with an anterior interbody cage support are as follows: 1) large segmental lordosis can decrease the stiffness of monoaxial pedicle screws constructs; 2) polyaxial screws rather than monoaxial screws combined with the cage fixation provide higher compression and flexion stiffness in 21° segmental lordosis; 3) polyaxial screws enhance the contact surface of the cage in 21° segmental lordosis. CONCLUSION: Polyaxial screws system used in conjunction with anterior cage support yields higher contact ratio, compression and flexion stiffness of spinal constructs than monoaxial screws system does in the same model when the spinal segment is set at large lordotic angles. Polyaxial pedicle screw fixation performs nearly equal percentages of vertebra-cage contact among all constructs with different sagittal alignments, therefore enhances the stabilization effect of interbody cages in the lumbosacral area

Alcohol use and health outcomes in the oldest old

BACKGROUND: As the United States population ages, an unprecedented proportion of the population will be aged 70 and older. Knowledge of alcohol use and its consequences in this age group is not well known. In light of the disparate findings pointing to negative outcomes with excessive drinking yet also benefits of moderate drinking, the true risk of alcohol use in late life needs more investigation. METHODS: This study examined the correlates and 2-year health outcomes related to alcohol use in 7,434 elders aged 70 years or older. Data was collected as part of the Assets and Health Dynamics of the Oldest Old (AHEAD), a nationwide health and economic study of elders. Data from Wave 1 and Wave 2 of AHEAD are presented. Frequency and quantity of drinking was assessed by self-report as was health status, lifetime alcohol or psychiatric problems, presence of chronic illness, functional impairment, and depressive symptoms. Cognitive status was assessed using a brief measure. RESULTS: Approximately 44% of the sample reported any alcohol use in the past three months, with the majority of drinking less than daily. Daily drinking was associated with being Caucasian, married, in relatively good health, and having good affective and cognitive status. Drinking was not associated with negative health outcomes two years later and was protective against stroke and functional impairment. Decline in drinking between Wave 1 and Wave 2 was strongly associated with poor health. CONCLUSION: This study offers no evidence of negative health outcomes for drinking moderately and confirms the U-shaped curve often found in studies of alcohol and health. Nonetheless, cessation of drinking was associated with poor health suggesting the health benefits of moderate drinking may result from selection of a healthy group of people capable of sustained moderate drinking. Public health recommendations for moderate drinking must take this phenomenon into account

Arp2/3 complex interactions and actin network turnover in lamellipodia

Cell migration is initiated by lamellipodia—membrane-enclosed sheets of cytoplasm containing densely packed actin filament networks. Although the molecular details of network turnover remain obscure, recent work points towards key roles in filament nucleation for Arp2/3 complex and its activator WAVE complex. Here, we combine fluorescence recovery after photobleaching (FRAP) of different lamellipodial components with a new method of data analysis to shed light on the dynamics of actin assembly/disassembly. We show that Arp2/3 complex is incorporated into the network exclusively at the lamellipodium tip, like actin, at sites coincident with WAVE complex accumulation. Capping protein likewise showed a turnover similar to actin and Arp2/3 complex, but was confined to the tip. In contrast, cortactin—another prominent Arp2/3 complex regulator—and ADF/cofilin—previously implicated in driving both filament nucleation and disassembly—were rapidly exchanged throughout the lamellipodium. These results suggest that Arp2/3- and WAVE complex-driven actin filament nucleation at the lamellipodium tip is uncoupled from the activities of both cortactin and cofilin. Network turnover is additionally regulated by the spatially segregated activities of capping protein at the tip and cofilin throughout the mesh