Endovascular treatment of spinal AVM: report of two cases with transvenous approach in combination with retrograde pressure cooker technique.

PURPOSE: Endovascular treatment of spinal AVMs is limited by low complete cure rates. Transarterial extensive treatment with liquid embolics carries the risk of clinically relevant ischemic complications. We report two cases of symptomatic spinal AVMs treated by a transvenous approach with retrograde pressure cooker technique. METHODS: In two selected cases, transvenous navigation aimed at retrograde pressure cooker embolization. RESULTS: Retrograde venous navigation was possible with two parallel microcatheters, and the pressure cooker technique with ethylenvinylalcohol-polymer was applicable in both cases. One AVM was occluded completely, and one subtotally due to a second draining vein. No clinical complications occurred. CONCLUSION: A transvenous approach for embolization with liquid embolics may offer advantages in treating certain spinal AVMs.

Synthesis and Biological Evaluation of C(13)/C(13')-Bis(desmethyl)disorazole†Z.

We describe the total synthesis of the macrodiolide C(13)/C(13')-bis(desmethyl)disorazole Z through double inter-/intramolecular Stille cross-coupling of a monomeric vinyl stannane/vinyl iodide precursor to form the macrocycle. The key step in the synthesis of this precursor was a stereoselective aldol reaction of a formal Evans acetate aldol product with crotonaldehyde. As demonstrated by X-ray crystallography, the binding mode of C(13)/C(13')-bis(desmethyl)disorazole Z to tubulin is virtually identical with that of the natural product disorazole Z. Likewise, C(13)/C(13')-bis(desmethyl)disorazole Z inhibits tubulin assembly with at least the same potency as disorazole Z and it appears to be a more potent cell growth inhibitor.

Association of nerve-sparing grading in robotic radical prostatectomy and trifecta outcome.

PURPOSE: To evaluate the neurovascular bundle preservation grades during robotic-assisted radical prostatectomy and compared to the trifecta combined outcome (oncologic control, continence, and sexual function) twelve months after the surgery. METHODS: Cohort of patients who underwent nerve-sparing robotic-assisted radical prostatectomy had the neurovascular bundle preservation retrospectively graded from 0 to 8 according to the Hopkins subjective visual classification. Patients then were divided into two groups, according to the median of nerve-sparing grading: those with score six or high and those with score less than six. Main outcome was the trifecta combined outcome and secondary outcomes was the individual trifecta criteria (prospective analysis). A secondary analysis with groups divided according to pre-operatory SHIM score was made. RESULTS: One hundred robotic-assisted nerve-sparing radical prostatectomy were performed, of which 83 were included. There were 53 patients with grading greater than or equal to six (group 1) and 30 patients less than six (group 2). 66.6% patients (35/53) in group 1 had a trifecta combined outcome of compared to 33.3% (10/30) in group 2 (p = 0.017). Individually, the erectile function was higher in group 1 (73.6%) compared to group 2 (46.7%) (p = 0.014). Both the results of the combined endpoint trifecta and erection were also maintained in the group with preoperative SHIM ≥ 17. CONCLUSIONS: The grading of preservation of the neurovascular bundle in radical prostatectomy is related to a better combined trifecta outcome one year after surgery.

Factores socioculturales de la vulnerabilidad al sobrepeso durante los primeros años de vida en México.

OBJETIVO: Analizar el rol de los factores socioeconómicos y culturales en la vulnerabilidad a la obesidad en madres y sus hijos menores de dos años, en localidades del Sur de Morelos, México. Material y métodos. Se realizó trabajo de campo y observación no participativa. Durante 2019, se aplicaron 17 entrevistas semiestructuradas a una submuestra de una cohorte. Los datos fueron ordenados y analizados con apoyo del software Atlas-Ti v. 7, usando 18 códigos libres. RESULTADOS: Factores sociales como los ingresos del hogar y los roles de género, combinados con la influencia de la parentela y las creencias sobre la preferencia de la niñez por productos ultraprocesados, predisponen la disponibilidad de bebidas y alimentos calóricos que generan vulnerabilidad a la obesidad durante la infancia temprana. La actividad eco-nómica de las madres, la participación de los padres y evitar influencia de parientes puede predisponer una mejor calidad de los alimentos y mayor actividad física. CONCLUSIONES: La baja disponibilidad de alimentos saludables, los riesgos de inseguridad alimentaria y los factores familiares y culturales, que se presentan en contextos de vulnerabilidad económica y social, incrementan la vulnerabilidad del binomio madre-hijo a la obesidad.

Synthesis of Morpholine-Based Analogues of (-)-Zampanolide and Their Biological Activity.

We describe the convergent synthesis of three prototypical examples of a new class of analogues of the complex, cytotoxic marine macrolide (-)-zampanolide that incorporate an embedded N-substituted morpholine moiety in place of the natural tetrahydropyran ring. The final construction of the macrolactone core was based on a high-yielding intramolecular HWE olefination, while the hemiaminal-linked side chain was elaborated through a stereoselective, BINAL-H-mediated addition of (Z,E)-sorbamide to a macrocyclic aldehyde precursor. The synthesis of the common functionalized morpholine building block involved two consecutive epoxide openings with tosylamide and the product of the first opening reaction, respectively, as nucleophiles. Of the three morpholino-zampanolides investigated, the N-acetyl and the N-benzoyl derivatives both exhibited nanomolar antiproliferative activity, thus being essentially equipotent with the natural product. In contrast, the activity of the N-tosyl derivative was significantly reduced.

Intraosseous contrast administration for emergency stroke CT.

Computed tomography (CT) imaging in acute stroke is an established and fairly widespread approach, but there is no data on applicability of intraosseous (IO) contrast administration in the case of failed intravenous (IV) cannula placement. Here, we present the first case of IO contrast administration for CT imaging in suspected acute stroke providing a dedicated CT examination protocol and analysis of achieved image quality as well as a review of available literature.

Impact of chorioamnionitis on maternal and fetal levels of proinflammatory S100A12.

Histologic chorioamnionitis (HCA) may lead to the fetal inflammatory response syndrome (FIRS). The aim of this pilot study was to evaluate S100A12, a marker of innate immune activation, in mothers with or without HCA and in their infants. Concentrations of S100A12, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated in maternal, cord, and neonatal blood of very preterm infants. Histologic examinations of the placenta and umbilical cords were performed. The 48 mother-neonate pairs enrolled were subdivided into two groups: HCA group (N = 15) and control group without HCA (N = 33). Maternal S100A12 levels were similar between HCA and control group. Similarly, S100A12 concentrations in cord and neonatal blood did not differ between the groups. However, high S100A12 concentrations were detected in cord and neonatal blood of two out of three neonates exposed to HCA associated with advanced funisitis. Concentrations of IL-6 and CRP were higher in maternal blood of the HCA group compared with controls (p < 0.05, p < 0.001; respectively), but no differences in cord or neonatal blood was found.Conclusion:S100A12 did neither identify mothers with HCA nor very preterm infants exposed to HCA. It is currently unknown if S100A12 may identify neonates with FIRS. What is known: • Histologic chorioamnionitis (HCA) may lead to the fetal inflammatory response syndrome (FIRS). • S100A12 represents an early, sensitive, and specific diagnostic marker of inflammatory processes. What is new: • S100A12 did neither identify mothers with HCA nor very preterm infants exposed to HCA. • It is currently still unclear if S100A12 has a potential in identifying preterm infants with FIRS.

Stakeholder analysis of the deliberation of an increase to the excise tax on sweetened beverages in Mexico.

OBJECTIVE: To present the results of a stakeholder analysis used to construct a map of the actors involved in the delib-eration of a proposal to increase the tax on sugar-sweetened beverages (SSB) in Mexico from 10 to 20 percent per liter. MATERIALS AND METHODS: A literature review and in-terviews to key actors were implemented. The analysis of the actors' power and position was made using Policymaker. RESULTS: There was concern for the obesity epidemic among all stakeholders, but little consensus on the way to solve it. Researchers and non-governmental organizations (NGO) support an increase in the tax on SSB, while government officials and industry representatives oppose this measure. CONCLUSION: Supporters of an increase to the tax on SSB need to build a coalition in order to force government officials to support this policy and successfully confront the soda industry, which has a solid opposing strategy and enormous financial resources to influence public opinion and congressmen.

Synthesis of Small-Molecule Fluorescent Probes for the In†Vitro Imaging of Calcium-Activated Potassium Channel KCa 3.1.

Small-molecule probes for the in vitro imaging of KCa 3.1 channel-expressing cells were developed. Senicapoc, showing high affinity and selectivity for the KCa 3.1 channels, was chosen as the targeting component. BODIPY dyes 15-20 were synthesized and connected by a CuI -catalyzed azide-alkyne [3+2]cycloaddition with propargyl ether senicapoc derivative 8, yielding fluorescently labeled ligands 21-26. The dimethylpyrrole-based imaging probes 25 and 26 allow staining of KCa 3.1 channels in NSCLC cells. The specificity was shown by removing the punctate staining pattern by pre-incubation with senicapoc. The density of KCa 3.1 channels detected with 25 and by immunostaining was identical. The punctate structure of the labeled channels could also be observed in living cells. Molecular modeling showed binding of the senicapoc-targeting component towards the binding site within the ion channel and orientation of the linker with the dye along the inner surface of the ion channel.

Drug release from thin films encapsulated by a temperature-responsive hydrogel.

Control over drug delivery may be interestingly achieved by using temperature responsive encapsulants, which change their thickness and mesh size with temperature. The prototype N-isopropylacrylamide hydrogel cross-linked with di(ethylene glycol) divinyl ether p(NIPAAm-co-DEGDVE) swells at low temperature and collapses above the lower critical solution temperature (LCST), ∼29 °C in a buffer. It might be expected that drug release from such encapsulation is always favored below the LCST, due to the larger free volume present in the swollen polymer film. Recent results show contradicting behavior where some cases behave as expected and others release much less when the polymer layer is swollen. In this study, layers of the drugs phenytoin, clotrimazole and indomethacin were drop cast on glass and p(NIPAAM-co-DEGDVE) layers were then synthesized directly on top of these drug layers via initiated chemical vapor deposition (iCVD), a solvent-free and gentle polymerization technique. Dissolution experiments were then performed, in which the drug release through the hindrance of the hydrogel was measured at different pH values. The results show that not only the swelling but also the permeate (drug in this case)-polymer interaction plays an important role in the release.

New in Vivo Compatible Matrix Metalloproteinase (MMP)-2 and MMP-9 Inhibitors.

Matrix metalloproteinases (MMPs) are emerging as pivotal fine-tuners of cell function in tissue homeostasis and in various pathologies, in particular inflammation. In vivo monitoring of the activity of specific MMPs, therefore, provides high potential for assessing disease progression and tissue function, and manipulation of MMP activity in tissues and whole organisms may further provide a mode of controlling pathological processes. We describe here the synthesis of novel fluorinated and nonfluorinated analogues of a secondary sulfonamide-based lead structure, compound 2, and test their efficacy as in vivo inhibitors and tracers of the gelatinases, MMP-2 and MMP-9. Using a murine neuroinflammatory model, we show that compound 2 is a highly effective in vivo inhibitor of both MMP-2 and MMP-9 activity with little or no adverse effects even after long-term daily oral administration. A fluorescein-labeled derivative compound 17 shows direct binding to activated gelatinases surrounding inflammatory cuffs in the neuroinflammation model and to pancreatic ß-cells in the islets of Langerhans, colocalizing with MMP-2 and MMP-9 activity as detected using in situ zymography techniques. These results demonstrate that compound 2 derivatives have potential as in vivo imaging tools and for future development for specific MMP-2 versus MMP-9 probes. Our chemical modifications mainly target the residues directed toward the S1' and S2' pockets and, thereby, provide new information on the structure-activity relationships of this inhibitor type.

Growing and Learning When Consumption Is Seasonal: Long-Term Evidence From Tanzania.

This article shows that the seasonality of food consumption during childhood, conditional on average consumption, affects long-run human capital development. We develop a model that distinguishes differences in average consumption levels, seasonal fluctuations, and idiosyncratic shocks, and estimate the model using panel data from early 1990s Tanzania. We then test whether the mean and seasonality of a child's consumption profile affect height and educational attainment in 2010. Results show that the negative effects of greater seasonality are 30 % to 60 % of the magnitudes of the positive effects of greater average consumption. Put differently, children expected to have identical human capital based on annualized consumption measures will have substantially different outcomes if one child's consumption is more seasonal. We discuss implications for measurement and policy.

Synthesis and evaluation of a [18F]BODIPY-labeled caspase-inhibitor.

BODIPYs (boron dipyrromethenes) are fluorescent dyes which show high stability and quantum yields. They feature the possibility of selective 18F-fluorination at the boron-core. Attached to a bioactive molecule and labeled with [18F]fluorine, the resulting compounds are promising tracers for multimodal imaging in vivo and can be used for PET and fluorescence imaging. A BODIPY containing a phenyl and a hydroxy substituent on boron was synthesized and characterized. Fluorinated and hydroxy substituted dyes were coupled to an isatin-based caspase inhibitor via cycloaddition and the resulting compounds were evaluated in vitro in caspase inhibition assays. The metabolic stability and the formed metabolites were investigated by incubation with mouse liver microsomes and LC-MS analysis. Subsequently the fluorophores were labeled with [18F]fluorine and an in vivo biodistribution study using dynamic PET was performed.

Solution of an elusive pigment crystal structure from a thin film: a combined X-ray diffraction and computational study.

Epindolidione, a hydrogen-bonded derivative of the organic semiconductor tetracene, is an organic pigment which has previously been used to produce stable OFETs with relatively high hole mobilities. Despite its use as an inkjet pigment and organic semiconductor, the crystal structure of epindolidione has proved elusive and is currently unknown. In this work, we report a crystal structure solution of epindolidione determined from vapor deposited thin films using a combined experimental and theoretical approach. The structure is found to be similar to one of the previously reported epindolidione derivatives and is most likely a surface-mediated polymorph, with a slightly different crystal packing compared to the bulk powder. The effect of substrate temperature on film morphology and structure is also investigated, where it is found that the crystallite orientation can be tuned by deposition at different substrate temperatures. The results also illustrate the possibilities for crystal structures to be solved from thin films.

Wrinkle formation in a polymeric drug coating deposited via initiated chemical vapor deposition.

Polymer encapsulation of drugs is conventionally used as a strategy for controlled delivery and enhanced stability. In this work, a novel encapsulation approach is demonstrated, in which the organic molecule clotrimazole is enclosed into wrinkles of defined sizes. Having defined wrinkles at the drug/encapsulant interface, the contact between the encapsulating polymer and the drug can be improved. In addition, this can also allow for some control on the drug delivery as the available surface area changes with the wrinkle size. For this purpose, thin films of clotrimazole were deposited onto silica substrates and were then encapsulated by crosslinked poly(2-hydroxyethyl methacrylate) (pHEMA) via initiated chemical vapor deposition (iCVD). The thickness and the solid state (crystalline or amorphous) of the clotrimazole layer were varied so that the conditions under which surface wrinkles emerge can be determined. A (critical) clotrimazole thickness of 76.6 nm was found necessary to induce wrinkles, whereby the wrinkle size is directly proportional to the thickness of the amorphous clotrimazole. When the pHEMA was deposited on top of crystalline clotrimazole instead, wrinkling was absent. The wrinkling effect can be understood in terms of elastic mismatch between the relatively rigid pHEMA film and the drug layer. In the case of amorphous clotrimazole, the relatively soft drug layer causes a large mismatch resulting in a sufficient driving force for wrinkle formation. Instead, the increased elastic modulus of crystalline clotrimazole reduces the elastic mismatch between drug and polymer, so that wrinkles do not form.

Acanthocephalan Parasites (Acanthogyrus sp.) of Nile Tilapia (Oreochromis niloticus) as Biosink of Lead (Pb) Contamination in a Philippine Freshwater Lake.

The potential use of acanthocephalans as bioindicators of Lead (Pb) pollution in Sampaloc Lake, Laguna, Philippines was investigated. Nile tilapias (Oreochromis niloticus) were collected and Pb concentrations were determined in fish tissues and in their acanthocephalan parasites, Acanthogyrus sp. Significantly higher levels of Pb were detected in the parasites relative to the fish host tissues (p = 0.001). Bioaccumulation capacity of the parasites against fish tissues were 102, 119, and 147 times higher than the fish intestine, liver, and muscles, respectively. Pb sensitivity of the parasites was quantified by exact logistic analysis showing higher odds of Pb detection ranging from 18 to 45 folds (p = 0.001-0.009). Interestingly, infected fish showed significantly lower Pb concentration in their tissues compared to uninfected fish (p = 0.001), suggesting parasites were able to sequester Pb and served as active biosinks. The Pb levels in the parasites were also hundred folds higher (988 times) relative to the ambient waters, indicating a potential role of fish parasites as metal biosinks in aquatic ecosystems.

Social innovation for the promotion of health equity.

The role of social innovations in transforming the lives of individuals and communities has been a source of popular attention in recent years. This article systematically reviews the available evidence of the relationship between social innovation and its promotion of health equity. Guided by Fair Foundations: The VicHealth framework for health equity and examining four types of social innovation--social movements, service-related social innovations, social enterprise and digital social innovations--we find a growing literature on social innovation activities, but inconsistent evaluative evidence of their impacts on health equities, particularly at the socio-economic, political and cultural level of the framework. Distinctive characteristics of social innovations related to the promotion of health equity include the mobilization of latent or unrealised value through new combinations of (social, cultural and material) resources; growing bridging social capital and purposeful approaches to linking individual knowledge and experience to institutional change. These have implications for health promotion practice and for research about social innovation and health equity.

Challenges to the development of taxation policies for sugar-sweetened beverages in Colombia.

Frequent consumption of sugar sweetened beverages (SSB) is related to the risks of developing overweight, obesity, cavities, diabetes and other diseases. Policies to significantly increase taxes on SSB have proven to be effective in reducing their consumption. The political debate on implementing these taxes in Colombia shows a series of barriers to placing this policy on the political agenda, and therefore, to its approval. This work analyses the political process involved in the struggle for the approval of an SBB tax in Colombia, as well as barriers and opportunities to putting it on the political agenda. This is done through a policy analysis with three research methods: a documentary analysis, political mapping of actors and semistructured interviews with key actors. Among the main findings, we have that actors who are in favour of the SSB tax stated that it is needed due to the health problems caused by SSB consumption, while those who opposed it argue that Colombia regulations are sufficient and already inform and educate consumers on excessive sugar consumption and its health implications. The Colombian political context is a barrier to SSB taxation, as the government favours and has a close connection with the food and SSB industry. In short, the policy issue has been reaching the agenda intermittently throughout the years. Nevertheless, new opportunities are arising after the COVID-19 pandemic and the 2022 administrative changes and further efforts from policy entrepreneurs are required to make this initiative progress in the political agenda.

A Giant Stent for Giant Cerebral Aneurysms-The Accero®-Rex-Stent.

OBJECTIVE: Until now, giant intracranial aneurysms (GIAs) have in many cases been a vascular disease that was difficult or impossible to treat, not least due to the lack of availability of a large-format stent. In this multicentre study, we report on the first five clinical applications of the Accero®-Rex-Stents (Acandis, Pforzheim, Germany) in the successful treatment of fusiform cerebral giant aneurysms. MATERIAL AND METHODS: The Accero®-Rex-Stents are self-expanding, braided, fully radiopaque Nitinol stents designed for aneurysm treatment. The stent is available in three different sizes (diameter 7-10 mm, length 30-60 mm) and intended for endovascular implantation in vessels with diameters of 5.5-10 mm. RESULTS: Five patients (all male, age 54.4 ± 8.1 years) with large fusiform aneurysms of the posterior circulation were treated endovascularly using the Accero®-Rex-Stents. There were no technical complications. One major ischemic complication occurred. A significant remodeling and reduction in the size of the stent-covered aneurysms was already seen in the short-term post-interventional course. CONCLUSIONS: The Accero®-Rex-Stents were successfully and safely implanted in all five patients with fusiform giant aneurysms, showing technical feasibility with promising initial results and significant aneurysm size reduction in already available follow-up imaging. KEY POINT: With the Accero-Rex-Stents, a new device is available that offers another treatment option for rare cerebral fusiform giant aneurysms with very large parent vessels.

Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow.

INTRODUCTION: Early neurological deterioration (END) is associated with poor outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Causes of END after mechanical thrombectomy (MT) include unsuccessful recanalization and reperfusion hemorrhages. However, little is known about END excluding the aforementioned causes. We aimed to investigate factors associated with unexplained END (ENDunexplained) with regard to the cerebral collateral status. PATIENTS AND METHODS: Multicenter retrospective study of AIS-LVO patients with successful MT (mTICI 2b-3). On admission CT angiography (CTA), pial arterial collaterals and venous outflow (VO) were assessed using the modified Tan-Scale and the Cortical Vein Opacification Score (COVES), respectively. ENDunexplained was defined as an increase in NIHSS score of ⩾ 4 within the first 24 hours after MT without parenchymal hemorrhage on follow-up imaging. Multivariable regression analyses were performed to examine factors of ENDunexplained and unfavorable functional outcome (modified Rankin Scale score 3-6). RESULTS: A total of 620 patients met the inclusion criteria. ENDunexplained occurred in 10% of patients. While there was no significant difference in pial arterial collaterals, patients with ENDunexplained exhibited more often unfavorable VO (81% vs. 53%; P < 0.001). Unfavorable VO (aOR [95% CI]; 2.56 [1.02-6.40]; P = 0.045) was an independent predictor of ENDunexplained. ENDunexplained was independently associated with unfavorable functional outcomes at 90 days (aOR [95% CI]; 6.25 [2.06-18.94]; P = 0.001). DISCUSSION AND CONCLUSION: Unfavorable VO on admission CTA was associated with ENDunexplained. ENDunexplained was independently linked to unfavorable functional outcomes at 90 days. Identifying AIS-LVO patients at risk of ENDunexplained may help to select patients for intensified monitoring and guide to optimal treatment regimes.