Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopamine controls Parkinson’s tremor by inhibiting the cerebellar thalamus

Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor. From a sample of 40 patients with Parkinson's disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson's tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range -12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role in Parkinson's tremor.aww331media15307619934001.
Postoperative serum attenuates LPS‐induced release of TNF‐α in orthopaedic surgery

Studies with ex vivo stimulation of whole blood samples from injured patients have revealed a diminished production capacity for a broad range of secretory products, including inflammatory cytokines. Recent interest has focused on the release of mediators in serum that depress the cell‐mediated immune response following trauma. The involvement of the lipid mediator prostaglandin E2 (PGE2) has been assumed because it is a potent endogenous immunosuppressor. In the present study, we tested the hypothesis that inhibitory substances circulating in the patient's serum after a major musculoskeletal trauma might impair leukocyte function by evaluating the effect of such serum on cytokine release in a whole blood model. Six females and three males undergoing elective total hip replacement were included in the study. Ex vivo LPS‐induced TNF‐α and IL‐10 were measured in whole blood sampled preoperatively and added serum taken before, at the end of operation, and at postoperative days 1 and 6 with saline as negative control. LPS induced significant releases of TNF‐α and IL‐10 in whole blood. Addition of preoperative, postoperative, and day‐1 postoperative serum did not alter the LPS‐induced release of TNF‐α as compared to saline. In the presence of serum from postoperative day 6, however, the expression of TNF‐α was significantly reduced as compared to saline and preoperative serum (p = 0.021 and 0.008, respectively). Neither of the serum samples altered the release of IL‐10. PGE2 was significantly (p = 0.008) increased in serum at postoperative day 6 as compared to preoperative levels. In conclusion, these data show that at day 6 after major orthopaedic surgery, the patient serum contained activity that inhibited ex vivo LPS‐induced TNF‐α release. The potent TNF‐α inhibitory activity found at day 6 after injury correlated with increased levels of PGE2 and indicates cell‐mediated hyporesponsiveness to a second stimulus. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1395–1400, 2007
One versus Two Venous Anastomoses in Microsurgical Free Flaps: A Meta-Analysis

Abstract Background Various reports suggest the augmentation of venous drainage through performing two venous anastomoses as a means of reducing the rate of thrombosis in free flap surgery. However, some suggest dual venous drainage may actually reduce venous blood flow velocity causing a potential risk for thrombosis. Methods On the basis of the Preferred Reporting Items for Systematics Reviews and Meta-analysis statement, a systematic search was conducted using PubMed and Medline databases. A total of 12,190 articles relating to “free flaps” and “one versus two venous anastomoses” were found between January 1992 and November 2012. Of the 12,190 articles, 23 studies were included in a meta-analysis performed using STATA 11.2 (StrataCorp, College Station, TX). Studies with case control groups for both single and double venous anastomoses and clearly defined results for flap failure and venous thrombosis were included. 95% confidence interval (CI) were calculated for each study and pooled in both fixed and random-effects models for both flap failure and venous thrombosis events. Results The analysis shows a significant reduction in flap failure (risk ratio, 0.64; 95% CI, 0.41–0.99; p = 0.03) and venous thrombosis (risk ratio, 0.66; 95% CI, 0.46–0.97; p = 0.047) when performing two venous anastomoses compared with one in free flap surgery. Conclusion The results show that performing two venous anastomoses is associated with a reduction in the incidence of flap failure by 36% and venous thrombosis by 34% compared with one venous anastomoses. Given that the performing of an additional venous anastomoses confers a lower risk of complication and is technically feasible, where possible two venous anastomoses should be performed in free flap procedures, however, this should be decided on a flap by flap basis.
Simulation-Based Neonatal and Infant Resuscitation Teaching: A Systematic Review of Randomized Controlled Trials

Abstract Background: Current resuscitation guidelines recommend the use of simulation-based medical education (SBME) as an instructional methodology to improve patient safety and health. We sought to investigate the evidence-base for the effectiveness of SBME for neonatal and pediatric resuscitation training. Method: Therefore, we conducted a systematic literature research of electronic databases (PubMed, EMBASE, Clinical Trials). Results: 13 randomized controlled trials with a total of 832 participants were identified. However, due to distinct differences in research objectives and varying outcome assessment a meta-analysis of studies could not be conducted. Eligible trials showed that SBME can enhance trainees’ cognitive, technical, and behavioral skills as well as self-confidence. Discussion/Conclusion:Skills acquired in the simulated environment can be integrated in clinical practice, and SBME might also lead to improved patient safety and health. Further research on SBME – especially investigating patient outcomes – is urgently required in order to strengthen these results and to establish a sound evidence-base for the effectiveness of SMBE for neonatal and infant resuscitation training.
Nutrient characteristics of Southwest Native American pre-contact diets

Southwest Native American pre-contact diets varied relative to water availability and subsequent distribution and density of plant and animal resources. Early paleolithic big game hunters consumed a diet high in fat and protein but low in carbohydrates and fiber. Big game extinction led to increased reliance on wild plant foods. Arid-land plants are high in complex carbohydrates, dietary fiber, hypoglycemic chemical compounds and antioxidant micronutrients. These characteristics enhance plant survival by improving water absorption and retention, by providing protection from predation and strong desiccating winds, and by producing colors attractive to potential pollinators. For Native Americans, wild plant foods provided a diet high in fiber, carbohydrates and micronutrients. In some locales, this emphasis on plant foods led to a shift to agriculture. The varieties of plants domesticated, predominantly corn, beans and squash, were lower in simple carbohydrates and higher in mineral content than modern comm.
Proteomic analysis of cells in the early stages of herpes simplex virus type‐1 infection reveals widespread changes in the host cell proteome

During infection by herpes simplex virus type‐1 (HSV‐1) the host cell undergoes widespread changes in gene expression and morphology in response to viral replication and release. However, relatively little is known about the specific proteome changes that occur during the early stages of HSV‐1 replication prior to the global damaging effects of virion maturation and egress. To investigate pathways that may be activated or utilised during the early stages of HSV‐1 replication, 2‐DE and LC‐MS/MS were used to identify cellular proteome changes at 6 h post infection. Comparative analysis of multiple gels representing whole cell extracts from mock‐ and HSV‐1‐infected HEp‐2 cells revealed a total of 103 protein spot changes. Of these, 63 were up‐regulated and 40 down‐regulated in response to infection. Changes in selected candidate proteins were verified by Western blot analysis and their respective cellular localisations analysed by confocal microscopy. We have identified differential regulation and modification of proteins with key roles in diverse cellular pathways, including DNA replication, chromatin remodelling, mRNA stability and the ER stress response. This work represents the first global comparative analysis of HSV‐1 infected cells and provides an important insight into host cell proteome changes during the early stages of HSV‐1 infection.
Virtual Expert Mass Spectrometrist: iTRAQ tool for database‐dependent search, quantitation and result storage

A frequent goal of MS‐based proteomics experiments nowadays is to quantify changes in the abundance of proteins across several biological samples. The iTRAQ labeling method is a powerful technique; when combined with LC coupled to MS/MS it allows relative quantitation of up to eight different samples simultaneously. Despite the usefulness of iTRAQ current software solutions have limited functionality and require the combined use of several software programs for analysis of the data from different MS vendors. We developed an integrated tool, now available in the virtual expert mass spectrometrist (VEMS) program, for database‐dependent search of MS/MS spectra, quantitation and database storage for iTRAQ‐labeled samples. VEMS also provides useful alternative report types for large‐scale quantitative experiments. The implemented statistical algorithms build on quantitative algorithms previously used in proposed iTRAQ tools as described in detail herein. We propose a new algorithm, which provides more accurate peptide ratios for data that show an intensity‐dependent saturation. The accuracy of the proposed iTRAQ algorithm and the performance of VEMS are demonstrated by comparing results from VEMS, MASCOT and PEAKS Q obtained by analyzing data from a reference mixture of six proteins. Users can download VEMS and test data from “http://www.portugene. com/software.html”.
Poly[[chlorido(1,10-phenanthroline-κ2N,N')copper(II)]-μ3-1,1,3,3-tetracyano-2-ethoxypropenido-κ3N:N':N'']: coordination polymer sheets linked into bilayers by hydrogen bonds.

In the title compound, [Cu(C9H5N4O)Cl(C12H8N2)]n or [Cu(tcnoet)Cl(phen)]n, where phen is 1,10-phenanthroline and tcnoet is 1,1,3,3-tetracyano-2-ethoxypropenide, the axially elongated (4 + 2) coordination polyhedron around the Cu(II) centre contains N atoms from three different tcnoet ligands. The resulting coordination polymer takes the form of sheets which are linked in pairs by a single C-H.N hydrogen bond to form bilayers. The bond lengths provide evidence for significant bond fixation in the phen ligand and extensive electronic delocalization in the tcnoet ligand, where the two -C(CN)2 units are rotated, in conrotatory fashion, out of the plane of the central C3O fragment.
Kommentar zu: Strobel U, Tami I, Andreisek G, et al. Vergleich der funktionellen Resultate mit MRT-Befunden nach operativer Versorgung von transskaphoidalen perilunären Luxationsfrakturen: Die Rolle von skapholunären Bandläsionen

Korrespondenzadresse Rainer Schmitt Klinik für Diagnostische und Interventionelle Radiologie Herzund Gefäß-Klinik GmbH Salzburger Leite 1 D-97616 Bad Neustadt rainer.schmitt@radiologie-badneustadt.de Kommentar zu: Strobel U, Tami I, Andreisek G, et al. Vergleich der funktionellen Resultate mit MRT-Befunden nach operativer Versorgung von transskaphoidalen perilunären Luxationsfrakturen: Die Rolle von skapholunären Bandläsionen Commentary on: Strobel U, Tami I, Andreisek G, et al. Comparison of Functional Results with MRI Findings after Surgical Treatment of Transscaphoid Perilunate Fracture Dislocations of the Wrist: The Role of Scapholunate Ligament Lesions
Comparative Study on Effects of Nebulized and Oral Salbutamol on a Cecal Ligation and Puncture-Induced Sepsis Model in Rats

Abstract Aim: The present study aimed to compare the effects of different routes of salbutamol administration (oral and nebulized) at different doses in a cecal ligation and puncture-induced (CLP-induced) sepsis model of rats. Methods: Rats were separated into 8 groups: 1) sham, 2) sham+4 mg/kg oral salbutamol, 3) sham+6 min 2 mg/ml nebulized salbutamol, 4) CLP, 5) CLP+2 mg/kg oral salbutamol, 6) CLP+4 mg/kg oral salbutamol, 7) CLP+3 min 2 mg/ml nebulized salbutamol, 8) CLP+6 min 2 mg/ml nebulized salbutamol. Subsequently, sepsis was induced by CLP through 16 h. Results: CLP-induced sepsis increased serum cytokine levels (TNF-α, IL-1β, and IL-6), increased tissue oxidative stress (8-Isoprosraglandin F2α), decreased antioxidant parameters (SOD, GSH), and increased lung injury by inflammatory cell accumulation. Conclusion: This study showed for the first time that oral administration of salbutamol exerted protective effects on CLP-induced sepsis and related lung injury in rats. We conclude that despite the greater side effects of oral salbutamol, it should be considered for administration in oral form due to its systemic effectiveness during septic conditions in emergency settings.
A new P,S-coordinating ferrocenyl ligand: synthesis of a precursor and its coordination compounds with Pd(II) and Pt(II).

In our ongoing development of ferrocene ligands, 1-dimethylamino-2-(diphenylphosphinothioyl)ferrocene is being used as a convenient building block to obtain racemic or enantiomerically pure ligands. Using this building block in large excess allowed the formation of several by-products, two of which have already been reported; the structure of a third by-product, namely 1-(diphenylphosphinothioyl)-2-{[(diphenylphosphinothioyl)sulfanyl]methyl}ferrocene, [Fe(C5H5)(C30H25P2S3)], is presented here. The crystal structure is built up from a ferrocene unit, with one of the cyclopentadienyl (Cp) rings substituted in the 1- and 2-positions by a protected diphenylphosphinothioyl group and a [(diphenylphosphinothioyl)sulfanyl]methyl fragment, -CH2SP(=S)Ph2. There are C-H.S interactions which result in the formation of chains parallel to the c axis. After desulfurization, the crude material was then reacted with Pd and Pt (M) precursors [MCl2(CH3CN)2] to yield two isostructural dinuclear complexes arranged around twofold axes, namely (R,R/S,S)-bis{μ-[2-(diphenylphosphanyl)ferrocen-1-yl]methanethiolato-κ(3)P,S:S}bis[chloridopalladium(II)] pentane disolvate, [Pd2{Fe(C5H5)(C18H15PS)}2Cl2]·2C5H12, and the platinum(II) analogue, (R,R/S,S)-bis{μ-[2-(diphenylphosphanyl)ferrocen-1-yl]methanethiolato-κ(3)P,S:S}bis[chloridoplatinum(II)] toluene monosolvate, [Pt2{Fe(C5H5)(C18H15PS)}2Cl2]·C7H8, in which the two metal atoms present a slightly distorted square-planar geometry formed by two bridging S atoms and P and Cl atoms. The P,S-chelating ligand results from the rupture of one of the P-S bonds in the starting ligand. These dinuclear complexes display a butterfly geometry. Surprisingly, only the (R,R/S,S) diastereoisomer has been isolated.
Ten Essential Points about Body Water Homeostasis

Background: Disorders of body fluids are among the most commonly encountered problems in the practice of clinical medicine. This is in large part because many different disease states can potentially disrupt the finely balanced mechanisms that control the intake and output of water and solute. It therefore behooves all clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. Since body water is the primary determinant of the osmolality of extracellular fluid, disorders of body water homeostasis can be divided into hypoosmolar disorders, in which there is an excess of body water relative to body solute, and hyperosmolar disorders, in which there is a deficiency of body water relative to body solute. The classic hyperosmolar disorder is diabetes insipidus, and the classic hypoosmolar disorder is the syndrome of inappropriate antidiuretic hormone secretion. Conclusions: Despite the complexity of this regulatory system, most disorders of water homeostasis can be understood by applying knowledge of the physiology and pathophysiology of arginine vasopressin (AVP) secretion and effects, as summarized in the ten essential points of this review. Understanding therapy for disorders of water homeostasis, including appropriate use of the new AVP receptor antagonists, can similarly be best understood by appreciating these same essential points.
Comparative physiological, ultrastructural and proteomic analyses reveal sexual differences in the responses of Populus cathayana under drought stress

Drought is a major abiotic stress, limiting the survival and growth of young plants. However, little is known about sex‐dependent responses to drought at the proteome level. In this study, we carried out investigations on comparative proteomics, combined with physiological and organelle structure analyses, in males and females of Populus cathayana Rehd. Three‐month‐old poplar cuttings were treated at 30% of field capacity and at 100% field capacity as a control in a greenhouse for 40 days. Drought greatly inhibited plant growth, damaged the photosynthetic system and destructed the structures of chloroplasts, mitochondria and cellular membranes. However, males suffered less from the adverse effects of drought than did females. Using 2‐DE, 563 spots were detected, of which 64 spots displayed significant drought effect and 44 spots displayed a significant sex by drought interaction effect. The results suggest that the different responses to drought stress detected between the sexes have a close relationship to the changes in the expression of sex‐dependent proteins, including, e.g. photosynthesis‐related proteins, homeostasis‐related proteins and stress response proteins. These proteins could contribute to a physiological advantage under drought, giving potential clues for understanding sexual differences in the performance of plants in different environments.
APOE ε4 allele is associated with reduced cerebrospinal fluid levels of Aβ42

The ε4 allele of APOE is a risk factor for Alzheimer disease (AD). By analysis of a large cohort of AD patients (n = 563) and control subjects (n = 118), it is shown that the ε4 allele is strongly associated with reduced CSF levels of β-amyloid (1–42) (Aβ42) in both AD (p < 10−9) and control (p = 0.0012) populations. As no associations of APOE variants with other indexes of AD severity were observed, this effect may reflect a fundamental involvement of ApoE in Aβ metabolism.
A domain level interaction network of amyloid precursor protein and Aβ of Alzheimer's disease

The primary constituent of the amyloid plaque, β‐amyloid (Aβ), is thought to be the causal “toxic moiety” of Alzheimer's disease. However, despite much work focused on both Aβ and its parent protein, amyloid precursor protein (APP), the functional roles of APP and its cleavage products remain to be fully elucidated. Protein–protein interaction networks can provide insight into protein function, however, high‐throughput data often report false positives and are in frequent disagreement with low‐throughput experiments. Moreover, the complexity of the CNS is likely to be under represented in such databases. Therefore, we curated the published work characterizing both APP and Aβ to create a protein interaction network of APP and its proteolytic cleavage products, with annotation, where possible, to the level of APP binding domain and isoform. This is the first time that an interactome has been refined to domain level, essential for the interpretation of APP due to the presence of multiple isoforms and processed fragments. Gene ontology and network analysis were used to identify potentially novel functional relationships among interacting proteins.
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis: Analysis of 37 Cases

Abstract Background At the time of diagnosis, lung cancer has often metastasized already. Brain metastases, however, are associated with a poor prognosis (median survival of less than 1 year). We evaluated the changes of the median survival after resection of the cerebral metastases and primary non-small cell lung cancer (NSCLC). Materials and Methods Between January 1999 and December 2009, 37 patients (22 men, 15 women; median age: 55.64 years; age range: 38–72 years) underwent surgery for primary NSCLC after craniotomy and removal of the synchronous single brain metastasis. The overall survival was evaluated and risk factors identified. Results Mediastinal lymph node involvement was excluded with mediastinoscopy in 26 of the 37 patients. Postoperative N-stage was N0, N1, and N2 in 16 (43%), 10 (27%), and 11 (30%) patients, respectively. Histology was squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell carcinoma in 7 (19%). The employed type of resection was anatomical segmentectomy in 6 and lobectomy in 31 patients. The 30-day mortality was 0% and postoperative complications occurred in 12 patients only (32%). The overall 1 and 2 years survival were 62 and 24%, respectively. None of the factors age, sex, tumor histology, primary location of the tumor, type of resection, adjuvant chemotherapy, or nodal status affected survival in the univariate analysis. Conclusions The oncologic lung resection of NSCLC after the resection of a single brain metastasis can be implemented without an increased risk of complications or mortality. Despite the stage IV disease, the median survival appears encouraging.
Maximal expiratory pressure and Valsalva manoeuvre do not produce similar cardiovascular responses in healthy men

What is the central question of this study? This is the first study to evaluate and describe the cardiovascular responses during maximal expiratory pressure compared with the Valsalva manoeuvre, and whether those responses are similar. What is the main finding and its importance? This study showed that the duration of the manoeuvres appears to be responsible for the different physiological mechanisms involved in the cardiovascular responses to each manoeuvre and that the intensity of expiratory effort was related to the response in maximal expiratory pressure. These results are important to identify the risks to which subjects are exposed when performing these manoeuvres.