Quantification of Cell Movement Reveals Distinct Edge Motility Types During Cell Spreading

Actin-based motility is central to cellular processes such as migration, bacterial engulfment, and cancer metastasis, and requires precise spatial and temporal regulation of the cytoskeleton. We studied one such process, fibroblast spreading, which involves three temporal phases: early, middle, and late spreading, distinguished by differences in cell area growth. In these studies, aided by improved algorithms for analyzing edge movement, we observed that each phase was dominated by a single, kinematically and biochemically distinct cytoskeletal organization, or motility type. Specifically, early spreading was dominated by periodic blebbing; continuous protrusion occurred predominantly during middle spreading; and periodic contractions were prevalent in late spreading. Further characterization revealed that each motility type exhibited a distinct distribution of the actin-related protein VASP, while inhibition of actin polymerization by cytochalasin D treatment revealed different dependences on barbed-end polymerization. Through this detailed characterization and graded perturbation of the system, we observed that although each temporal phase of spreading was dominated by a single motility type, in general cells exhibited a variety of motility types in neighboring spatial domains of the plasma membrane edge. These observations support a model in which global signals bias local cytoskeletal biochemistry in favor of a particular motility type

Progressive subacute Miller-Fisher syndrome successfully treated with plasmapheresis

Background Miller-Fisher Syndrome (MFS) is a rare acute polyneuropathy composed of the clinical triad of ataxia, areflexia and ophthalmoplegia, with a monophasic, self-limited course and spontaneous improvement. Case report The authors present a 65-year-old man with Miller-Fisher syndrome consisting of bilateral ophthalmoplegia, trigeminal and facial nerve palsy, mild ataxia and peripheral neuropathy. The disease had a progressive, subacute course within 3 months. A high titer of anti-GQ1b antibodies was detected. As a result of plasmapheresis, complete recovery was achieved. Conclusions The presented case was atypical in its clinical course and treatment. It could support the theory of the continuity between MFS, Bickerstaff brainstem encephalitis (BBE), and Guillain–Barré syndrome (GBS)

Strong Anionic/Charge-Neutral Block Copolymers from Cu(0)-Mediated Reversible Deactivation Radical Polymerization

[Image: see text] Despite recent developments in controlled polymerization techniques, the straightforward synthesis of block copolymers that feature both strong anionic and charge-neutral segments remains a difficult endeavor. In particular, solubility issues may arise during the direct synthesis of strong amphiphiles and typical postpolymerization deprotection often requires harsh conditions. To overcome these challenges, we employed Cu(0)-mediated reversible deactivation radical polymerization (Cu(0)-RDRP) on a hydrophobic isobutoxy-protected 3-sulfopropyl acrylate. Cu(0)-RDRP enables the rapid synthesis of the polymer, reaching high conversions and low dispersities while using a single solvent system and low amounts of copper species. These macromolecules are straightforward to characterize and can subsequently be deprotected in a mild yet highly efficient fashion to expose their strongly charged nature. Furthermore, a protected sulfonate segment could be grown from a variety of charge-neutral macroinitiators to produce, after the use of the same deprotection chemistry, a library of amphiphilic, double-hydrophilic as well as thermoresponsive block copolymers (BCPs). The ability of these various BCPs to self-assemble in aqueous media was further studied by dynamic light scattering, ζ-potential measurements as well as atomic force and electron microscopy

Safety and efficacy of treatment of very small intracranial aneurysms

Purpose: Very small intracranial aneurysms (VSIAs) may cause many neurological complications and even death. Thanks to technological progress and higher quality of non-invasive neuroimaging methods, these pathologies can be investigated sooner and treated earlier. Due to the controversy surrounding invasive treatment of these pathologies, the aim of the study was to analyse methods of treatment, their outcome, and complications in a group of patients with VSIAs. Material and methods: Out of 444 cases of intracranial aneurysms treated in our centre, 65 aneurysms met the radiological criteria of VSIAs. The parameters - width and length of the aneurysm's neck and width, length, and height of the aneurysm's dome - were measured. The analysed parameters were as follows: symptoms upon admission and after treatment, days in hospital, and intraoperative complications. Clinical and radiological intensity of subarachnoid haemorrhage (SAH) was evaluated by using the Hunt-Hess and Fisher scales. The degree of embolisation of the aneurysm after the procedure was assessed using the Montreal Scale. Clinical outcome was assessed by Glasgow Outcome Scale. Results: 50.77% of VSIAs were treated with endovascular procedures and 49.23% with neurosurgical clipping. SAH was presented in 38.46% of patients with VSIAs. Intraoperative complications were presented in 16.92% of patients with VSIAs, and the most common complication was ischaemic stroke. Stents were used in 51.52% of VSIAs. In 69.70% of embolisation procedures at VSIAs complete obliteration was achieved. The average result in the Montreal Scale was 1.31 (SD = 0.66). Conclusion: VSIAs can be treated as effectively and safely as larger aneurysms, by both endovascular and surgical methods

Idiopatyczne nadciśnienie śródczaszkowe u młodej kobiety bez nadwagi

Idiopatyczne nadciśnienie śródczaszkowe to stan charakteryzującysię wzmożonym ciśnieniem prawidłowego płynu mózgowo-rdzeniowego(> 250 mm H2O), któremu nie towarzyszy inny procespatologiczny toczący się w układzie nerwowym lub poza nim.W rozważaniach nad patogenezą schorzenia bierze się pod uwagęmiędzy innymi rolę żeńskich hormonów płciowych, otyłości,nadkrzepliwości krwi oraz zaburzeń krążenia płynu mózgowo--rdzeniowego. Większość chorych z idiopatycznym nadciśnieniemśródczaszkowym skarży się na obustronny ból głowy. Podstawowym,obiektywnym objawem schorzenia jest obrzęk tarcz nerwówwzrokowych, który w przypadku długotrwałego utrzymywaniasię prowadzi do uszkodzenia nerwów wzrokowych i zaburzeńwidzenia. Dlatego konieczna jest regularna kontrola okulistycznaz oceną dna oka, badaniem ostrości wzroku, pola widzeniai rozróżniania barw. Leczenie idiopatycznego nadciśnienia śródczaszkowegoobejmuje redukcję masy ciała, stosowanie lekówzmniejszających wytwarzanie płynu mózgowo-rdzeniowego orazpostępowanie neurochirurgiczne. Autorzy przedstawiają młodąchorą bez nadwagi z przygodnie rozpoznanym idiopatycznymnadciśnieniem śródczaszkowym

Nowotworowe zapalenie opon mózgowo-rdzeniowych — opis dwóch przypadków

Do zajęcia opon mózgowo-rdzeniowych, określanego również jako meningoza lub karcynomatoza opon, dochodzi u 5–8% pacjentów z chorobami nowotworowymi. Przerzuty do opon miękkich występują w przebiegu złośliwych nowotworów układu krwiotwórczego,raka sutka, raka płuca, czerniaka i gruczolakoraków przewodu pokarmowego. Meningoza przebiega pod postacią rakowatości opon i rdzenia kręgowego lub nowotworowego zapalenia opon mózgowo-rdzeniowych, które różnią się przebiegiem klinicznymi rokowaniem. Charakterystyczną cechą nowotworowego zapalenia opon mózgowo-rdzeniowych jest jednoczesne, wielopoziomowe występowanie objawów klinicznych wynikających z zajęcia kilku obszarów układu nerwowego. Średni czas przeżycia pacjentów z nowotworowym zapaleniem opon mózgowo-rdzeniowych wynosi 4–11 tygodni. Mimo postępu diagnostyki i leczenia onkologicznego w ostatnich kilkudziesięciu latach czas ten nie uległ wydłużeniu. Autorzy przedstawili opisy dwóch pacjentów z nowotworowym zapaleniem opon mózgowo-rdzeniowych (w przebiegu czerniaka i raka płuca)

Cost-effectiveness of CTA, MRA and DSA in patients with non-traumatic subarachnoid haemorrhage

OBJECTIVES: Intra-arterial digital subtraction angiography (DSA), magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) are imaging modalities used for diagnostic work-up of non-traumatic subarachnoid haemorrhage. The aim of our study was to compare the cost-effectiveness of MRA, DSA and CTA in the first year after the bleed. METHODS: A decision model was used to calculate costs and benefits (in quality-adjusted life-years [QALYs]) that accrued to cohorts of 1,000 patients. Costs and characteristics of diagnostic tests, therapy, patients’ quality of life and associated costs were respected. The diagnostic strategy with highest QALYs and lowest costs was considered most cost-effective. RESULTS: DSA was the most effective diagnostic option, yielding on average 0.6039 QALYs (95 % CI, 0.5761–0.6327) per patient, followed by CTA 0.5983 QALYs (95 % CI, 0.5704–0.6278) and MRA 0.5947 QALYs (95 % CI, 0.5674–0.6237). Cost was lowest for DSA (39,808 €; 95 % CI, 37,182–42,663), followed by CTA (40,748 €; 95 % CI, 37,937–43,831) and MRA (41,814 €; 95 % CI, 38,730–45,146). A strategy of CTA followed by DSA if CTA was negative or coiling deemed not feasible, was as effective as DSA alone at average costs of 39,767€ (95 % CI, 36,903–42,402). CONCLUSION: A combined strategy of CTA and DSA was found to be the most cost-effective diagnostic approach. MAIN MESSAGES: • We defined a standard model for cost-effectiveness analysis in diagnostic imaging. • Comparing total 1-year health costs and benefits, CTA is superior to MRA. • A strategy of combining CTA and DSA was found to be the most cost-effective diagnostic approach

The genetic prehistory of the Andean highlands 7000 years BP though European contact

The peopling of the Andean highlands above 2500 m in elevation was a complex process that included cultural, biological, and genetic adaptations. Here, we present a time series of ancient whole genomes from the Andes of Peru, dating back to 7000 calendar years before the present (BP), and compare them to 42 new genome-wide genetic variation datasets from both highland and lowland populations. We infer three significant features: A split between low- And high-elevation populations that occurred between 9200 and 8200 BP; a population collapse after European contact that is significantly more severe in South American lowlanders than in highland populations; and evidence for positive selection at genetic loci related to starch digestion and plausibly pathogen resistance after European contact. We do not find selective sweep signals related to known components of the human hypoxia response, which may suggest more complex modes of genetic adaptation to high altitude

A Novel Standardized Method for Aiding to Determine Left Atrial Enlargement on Lateral Thoracic Radiographs in Dogs

BACKGROUND: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. METHODS: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. RESULTS: The new method moderately correlated with LA:Ao (r = 0.56-0.66) in all groups. The diagnostic accuracy (72-74%) of the subjective assessment and the new method showed no difference. CONCLUSIONS: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation