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LIMK1 and LIMK2 is enriched within the tumor in NT animals but diminished in LIMK1/2 KD tumors.

The aggressive brain tumor glioblastoma (GBM) is characterized by rapid cellular infiltration of brain tissue, raising the possibility that disease progression could potentially be slowed by disrupting the machinery of cell migration. The LIM kinase isoforms LIMK1 and LIMK2 (LIMK1/2) play important roles in cell polarization, migration, and invasion and are markedly upregulated in GBM and many other infiltrative cancers. Yet, it remains unclear whether LIMK suppression could serve as a viable basis for combating GBM infiltration. In this study, we investigated effects of LIMK1/2 suppression on GBM invasion by combining GBM culture models, engineered invasion paradigms, and mouse xenograft models. While knockdown of either LIMK1 or LIMK2 only minimally influenced invasion in culture, simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells (TIC) in both Boyden chamber and 3D hyaluronic acid spheroid invasion assays. Furthermore, LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis. In an orthotopic xenograft model, TICs stably transduced with LIMK1/2 shRNA were implanted intracranially in immunocompromised mice. Tumors derived from LIMK1/2 knockdown TICs were substantially smaller and showed delayed growth kinetics and more distinct margins than tumors derived from control TICs. Overall, LIMK1/2 suppression increased mean survival time by 30%. These findings indicate that LIMK1/2 strongly regulate GBM invasive motility and tumor progression and support further exploration of LIMK1/2 as druggable targets.Significance:Targeting the actin-binding proteins LIMK1 and LIMK2 significantly diminishes glioblastoma invasion and spread, suggesting the potential value of these proteins as therapeutic targets.

Supplemental Video 1. LIMK1/2 KD U373s exhibit abnormal actin turnover

Sequences of shRNAs expressed by LIMK1/2 knockdown cells.

Colonic polyp surveillance guidelines are based on data from patients 50 and above. Given the recent lowering for colorectal cancer (CRC) screening to age 45, the aim of this study was to assess whether existing colonic polyp surveillance guidelines are appropriate to use in younger patients.We performed a retrospective cohort study of patients who underwent 2 colonoscopies within a 10-year period. Five Risk Stratification Groups (RSG) were developed based on surveillance colonoscopy interval times recommended by the US Multi-Society Task Force (USMSTF) on CRC, and changes in RSG from index to surveillance colonoscopy were compared between 3 age cohorts-those below 45, those 45 to 49, and those 50 and above. Further analysis was performed for patients whose RSG worsened from index to surveillance colonoscopy, as this was defined as an inappropriate surveillance interval.A total of 1895 patients were included in the final analysis. A multivariate regression model showed that a worsened RSG was not significantly associated with age group, both when comparing below 45 to those 50 and above [odds ratio (OR)=0.840, 95% confidence interval (CI): 0.504-1.399, P=0.50] and when comparing those 45 to 49 to those 50 and above (OR=1.416, 95% CI: 0.905-2.216, P=0.13). Only being female was found to be statistically associated with worsened RSG after controlling for other variables (OR=0.652, 95% CI: 0.486-0.875, P0.01).Our study found that younger cohorts of patients, both below 45 and those 45 to 49, are not statistically more likely to develop more advanced polyps necessitating a shorter time to surveillance colonoscopy compared with patients 50 years and above. This finding supports using existing colonic polyp surveillance colonoscopy guidelines that were developed for patients 50 years and above in both patients below 45 and those 45 to 49 years old.

Ukraine is among the countries with a high prevalence of acute chemical etiology poisoning in the countries of the European region, taking the penultimate place according to WHO (2017). The Aim of the Research. To study the risk factors for acute domestic poisoning among children and adolescents in Ukraine and to identify measures to improve it. Methods and Materials. The annual statistical reports of WHO, the data of the State Statistics Committee of Ukraine, the Center for Medical Statistics of the Ministry of Healthcare of Ukraine, and statistics of the Department of acute poisoning of the NCSH «Okhmatdyt» were analyzed. Research methods: system approach and benchmarking were applied. Results and Discussion. A comparative estimate of the incidence of acute poisoning over the last 15 years in Ukraine indicates an overall tendency for their growth as a whole: in the group of children 0–14 years, an average of 10.4% (from 13.8 ± 0.05 cases / 10000 in 1996–1998 to 15.4 ± 0.1 cases / 10000 pediatric population in 2006–2010). Among children aged 0–4 years, the rate of increase in the number of acute poisonings was the highest, i.e. it increased from 31.7 ± 0.1 to 37.1 ± 0.2 cases / 10000 of the pediatric population of this age. The incidence of primary diseases of the pediatric population, according to the data of the Injury and Poisoning statistical group, has been practically at the same level in recent years, with a slight upward trend. Thus, over the last 20 years the incidence has fluctuated within 39.6–51.4 cases / 10000 population. Conclusions. An important factor in the emergence of household poisoning is the lack of motivation of the population, including children and adolescents, to lead a healthy lifestyle (including maintaining a healthy diet). Key Words: chemical safety, food safety, toxicology, acute poisoning.

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

The aggressive brain tumor glioblastoma (GBM) is characterized by rapid cellular infiltration of brain tissue, raising the possibility that disease progression could potentially be slowed by disrupting the machinery of cell migration. The LIM kinase isoforms LIMK1 and LIMK2 (LIMK1/2) play important roles in cell polarization, migration, and invasion and are markedly upregulated in GBM and many other infiltrative cancers. Yet, it remains unclear whether LIMK suppression could serve as a viable basis for combating GBM infiltration. In this study, we investigated effects of LIMK1/2 suppression on GBM invasion by combining GBM culture models, engineered invasion paradigms, and mouse xenograft models. While knockdown of either LIMK1 or LIMK2 only minimally influenced invasion in culture, simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells (TIC) in both Boyden chamber and 3D hyaluronic acid spheroid invasion assays. Furthermore, LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis. In an orthotopic xenograft model, TICs stably transduced with LIMK1/2 shRNA were implanted intracranially in immunocompromised mice. Tumors derived from LIMK1/2 knockdown TICs were substantially smaller and showed delayed growth kinetics and more distinct margins than tumors derived from control TICs. Overall, LIMK1/2 suppression increased mean survival time by 30%. These findings indicate that LIMK1/2 strongly regulate GBM invasive motility and tumor progression and support further exploration of LIMK1/2 as druggable targets. Significance: Targeting the actin-binding proteins LIMK1 and LIMK2 significantly diminishes glioblastoma invasion and spread, suggesting the potential value of these proteins as therapeutic targets.

We report a case of an asymptomatic 40-year-old African American male who was referred to our clinic for evaluation of bilateral macular drusen. Medical history was remarkable only for diabetes mellitus type 1. Fundoscopy revealed a peculiar, bilateral pigmentary maculopathy. Further imaging included autofluorescence imaging that showed an irregular hypo- and hyperautofluorescent pattern consistent with severe retinal pigment epithelial (RPE) dysfunction. Optical coherence tomography supported outer retinal layer loss and RPE atrophy. Fluorescein angiography and electroretinography were also performed. Further discussion with the patient yielded a family history where 4 older siblings died in their teenage years from strokes and seizures. The patient was referred to a geneticist who ultimately diagnosed him with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, and genetic testing of his mitochondrial deoxyribonucleic acid identified an A3234G point mutation in the MT-TL1 gene.

The authors report multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO) (Apaeros retinal image system AOSLO prototype; Boston Micromachines Corporation, Boston, MA) in a case of previously diagnosed unilateral acute idiopathic maculopathy (UAIM) that demonstrated features of laser pointer maculopathy. The authors also show the adaptive optics images of a laser pointer maculopathy case previously reported. A 15-year-old girl was referred for the evaluation of a maculopathy suspected to be UAIM. The authors reviewed the patient's history and obtained fluorescein angiography, autofluorescence, optical coherence tomography, infrared reflectance, and AOSLO. The time course of disease and clinical examination did not fit with UAIM, but the linear pattern of lesions was suspicious for self-inflicted laser pointer injury. This was confirmed on subsequent questioning of the patient. The presence of linear lesions in the macula that are best highlighted with multimodal imaging techniques should alert the physician to the possibility of laser pointer injury. AOSLO further characterizes photoreceptor damage in this condition. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:782–785.]