Endovascular intervention for acute thromboembolic stroke in young patients: an ideal population for aggressive intervention?

OBJECT: Endovascular treatment of acute thromboembolic stroke is a rapidly developing field that appears to hold great promise. Young patients may be particularly suited to benefit from endovascular acute stroke therapy. The authors sought to identify outcomes in young patients with thromboembolic stroke who underwent endovascular intervention. METHODS: The authors retrospectively reviewed a prospectively collected endovascular intervention registry of patients with ischemic strokes treated at a single large-volume institution between December 2000 and June 2007 to identify patients 18-35 years of age who were treated for thromboembolic stroke. Data are presented as the mean +/- standard deviation unless otherwise noted. RESULTS: Seven young patients underwent 8 consecutive endovascular interventions for thromboembolic stroke (mean age 26 +/- 6 years; 5 women). The National Institutes of Health Stroke Scale score at presentation was 13 +/- 4.3 (median 13). All patients presented within 6 hours of symptom onset. Revascularization was attempted with mechanical thrombectomy/disruption, intraarterial thrombolysis, and/or angioplasty, with or without stent placement. The modified Rankin Scale (mRS) score at discharge was 2.2 +/- 1.5 (median 1.5), with 5 patients (62.5%) achieving independence at discharge (mRS Score 0-2). There were no deaths. Hospital length of stay was 6.5 +/- 3.7 days (4.4 +/- 1.5 days for patients with an mRS score of 0-2; 10 +/- 3.6 days for patients with an mRS score of 4). All patients became independent and had reached an mRS score of < or = 2 at last follow-up evaluation (29 +/- 25 months). CONCLUSIONS: The data demonstrate the relative safety of endovascular intervention in young patients with thromboembolic cerebral ischemia and may suggest a potential benefit in outcome. Further investigation is indicated with larger numbers of patients and an appropriate control population.     

Varying environments can speed up evolution

Simulations of biological evolution, in which computers are used to evolve systems toward a goal, often require many generations to achieve even simple goals. It is therefore of interest to look for generic ways, compatible with natural conditions, in which evolution in simulations can be speeded. Here, we study the impact of temporally varying goals on the speed of evolution, defined as the number of generations needed for an initially random population to achieve a given goal. Using computer simulations, we find that evolution toward goals that change over time can, in certain cases, dramatically speed up evolution compared with evolution toward a fixed goal. The highest speedup is found under modularly varying goals, in which goals change over time such that each new goal shares some of the subproblems with the previous goal. The speedup increases with the complexity of the goal: the harder the problem, the larger the speedup. Modularly varying goals seem to push populations away from local fitness maxima, and guide them toward evolvable and modular solutions. This study suggests that varying environments might significantly contribute to the speed of natural evolution. In addition, it suggests a way to accelerate optimization algorithms and improve evolutionary approaches in engineering.     

Pharmacotherapy for Fecal Incontinence: A Review

Fecal incontinence is a common clinical problem that often is frustrating to the patient and treating physician. Nonsurgical management for fecal incontinence includes dietary manipulation, Kegel exercises, perianal skin care, and biofeedback therapy. Pharmacotherapies often are used to assist in management of fecal incontinence. A variety of pharmacotherapies have been utilized for the management of fecal incontinence; limited data from randomized, placebo-controlled trials are available. This is a review of the existing literature on clinical trials of several classes of drugs and other medical therapies that may be beneficial for patients with fecal incontinence. The information in this article was obtained by a MEDLINE search for all clinical trials of drug therapy for fecal incontinence. These treatments and the existing data on their use are summarized. Treatments reviewed include stool bulking agents, with an emphasis on the most promising effect obtained with calcium polycarbophil, constipating agents, including loperamide, codeine, amitriptyline, atropine, and diphenoxylate agents injected into the anal sphincter, drugs to enhance anal sphincter function, including topical phenylepherine and oral sodium valproate, and trials of fecal disimpaction. A new classification to easily remember the treatment categories for this condition, based on the "ABCs of treatment for fecal incontinence," has been introduced into the structure of this review.     

Anti-β<Subscript>2</Subscript>-glycoprotein I in Sjogren’s syndrome is associated with parkinsonism

The nervous system may be involved in up to 30% of patients with Sjogren’s syndrome (SS). We describe three patients with Sjogren’s syndrome and a concomitant parkinsonian syndrome. Elevated titers of anti-β₂-glycoprotein I IgG were found in the serum of all three patients. This autoantibody is strongly associated with anticardiolipin (aCL) antibodies, antiphospholipid syndrome (APS), and thromboembolic phenomena, but its role in the pathogenesis of the parkinsonian disorder in SS is unclear. These patients may present a subtype of SS patients in which the presence of aCL antibodies is associated with central nervous system involvement predominantly in the basal ganglia. Sharon Hassin-Baer and Levy Yair contributed equally to this work.     

Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with computerized tomography presentation

The aim of this study was to correlate clinical and computerized tomography (CT) features of bisphosphonate-related osteonecrosis of the jaws (BRONJ). All ONJ patients for whom there was complete CT scan imaging were eligible. Selected clinical parameters retrieved from their medical records were analyzed for correlation with CT parameters. The clinical presentation of BRONJ was supported by findings in CT imaging in 78.3%. The lesion’s size on CT correlated with the presence of purulent secretion (p?=?0.03). When sequestrum was present, the median lesion’s size on CT was relatively big (28 mm, range 21–43 mm). The mandibular canal cortex was never breached. CT has reasonable detection competence for diagnosing BRONJ. Purulent secretion indicates the likelihood that a more extensive involvement will be displayed on CT. A large lesion on CT should raise the index of suspicion for sequestrum. The CT appearance of a continuous cortex of the mandibular canal may serve as a differential parameter between BRONJ and metastasis to the jaw.     

Design and analysis of synthetic carbon fixation pathways

Carbon fixation is the process by which CO₂ is incorporated into organic compounds. In modern agriculture in which water, light, and nutrients can be abundant, carbon fixation could become a significant growth-limiting factor. Hence, increasing the fixation rate is of major importance in the road toward sustainability in food and energy production. There have been recent attempts to improve the rate and specificity of Rubisco, the carboxylating enzyme operating in the Calvin–Benson cycle; however, they have achieved only limited success. Nature employs several alternative carbon fixation pathways, which prompted us to ask whether more efficient novel synthetic cycles could be devised. Using the entire repertoire of approximately 5,000 metabolic enzymes known to occur in nature, we computationally identified alternative carbon fixation pathways that combine existing metabolic building blocks from various organisms. We compared the natural and synthetic pathways based on physicochemical criteria that include kinetics, energetics, and topology. Our study suggests that some of the proposed synthetic pathways could have significant quantitative advantages over their natural counterparts, such as the overall kinetic rate. One such cycle, which is predicted to be two to three times faster than the Calvin–Benson cycle, employs the most effective carboxylating enzyme, phosphoenolpyruvate carboxylase, using the core of the naturally evolved C4 cycle. Although implementing such alternative cycles presents daunting challenges related to expression levels, activity, stability, localization, and regulation, we believe our findings suggest exciting avenues of exploration in the grand challenge of enhancing food and renewable fuel production via metabolic engineering and synthetic biology.     

Long-lived quantum coherence in photosynthetic complexes at physiological temperature

Photosynthetic antenna complexes capture and concentrate solar radiation by transferring the excitation to the reaction center that stores energy from the photon in chemical bonds. This process occurs with near-perfect quantum efficiency. Recent experiments at cryogenic temperatures have revealed that coherent energy transfer—a wave-like transfer mechanism—occurs in many photosynthetic pigment-protein complexes. Using the Fenna–Matthews–Olson antenna complex (FMO) as a model system, theoretical studies incorporating both incoherent and coherent transfer as well as thermal dephasing predict that environmentally assisted quantum transfer efficiency peaks near physiological temperature; these studies also show that this mechanism simultaneously improves the robustness of the energy transfer process. This theory requires long-lived quantum coherence at room temperature, which never has been observed in FMO. Here we present evidence that quantum coherence survives in FMO at physiological temperature for at least 300 fs, long enough to impact biological energy transport. These data prove that the wave-like energy transfer process discovered at 77 K is directly relevant to biological function. Microscopically, we attribute this long coherence lifetime to correlated motions within the protein matrix encapsulating the chromophores, and we find that the degree of protection afforded by the protein appears constant between 77 K and 277 K. The protein shapes the energy landscape and mediates an efficient energy transfer despite thermal fluctuations.     

Plasminogen,human-tvmh for the treatment of children and adults with plasminogen deficiency type 1

Aim

An open-label phase 2/3 study of plasminogen, human-tvmh administered intravenously in paediatric and adult subjects with type 1 plasminogen deficiency was conducted. Interim data was previously reported. The final data on 15 subjects who completed the study up to a maximum of 124 weeks are reported here.

Methods

The primary objectives were to evaluate efficacy of plasminogen replacement therapy on clinically evident or visible lesions during 48 weeks of dosing and to achieve an increase in trough plasminogen activity levels by at least an absolute 10% above baseline during 12 weeks of treatment.

Results

The primary efficacy endpoint was achieved, as 100% of subjects (n = 11) with visible and assessable non-visible lesions at baseline demonstrated ≥ 50% improvement after 48 weeks of study drug treatment with plasminogen, human-tvmh. All subjects achieved the targeted ≥ 10% increase in trough plasminogen activity above baseline through Week 12. Plasminogen, human-tvmh at a dose of 6.6 mg/kg administered every 2–5 days for 48 weeks and every 1–7 days for up to 124 weeks was well tolerated.

Conclusion

This study provides additional evidence regarding the long-term safety and clinical utility of replacement therapy with human plasminogen for the treatment of children and adults with type 1 plasminogen deficiency. Plasminogen, human-tvmh received marketing approval on June 4, 2021. This trial was registered at www.clinicaltrials.gov as #NCT02690714.