Autochthonous Crimean-Congo Hemorrhagic Fever in Spain.

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, viral, tickborne disease. In Europe, cases have been reported only in the southeastern part of the continent. We report two autochthonous cases in Spain. The index patient acquired the disease through a tick bite in the province of Ávila - 300 km away from the province of Cáceres, where viral RNA from ticks was amplified in 2010. The second patient was a nurse who became infected while caring for the index patient. Both were infected with the African 3 lineage of this virus. (Funded by Red de Investigación Cooperativa en Enfermedades Tropicales [RICET] and Efficient Response to Highly Dangerous and Emerging Pathogens at EU [European Union] Level [EMERGE].).

Pentamidine antagonizes the benznidazole's effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target.

Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T. cruzi. In isolated trypomastigotes, we performed a dose-matrix scheme of combinations, where pentamidine antagonized the effect of benznidazole, mainly at concentrations below the EC50 of pentamidine. In T. cruzi-infected mammalian cells, pentamidine reversed the effect of benznidazole (measured by qPCR). In comparison, in infected BALB/c mice, pentamidine failed to get synergy with benznidazole, measured on mice survival, parasitemia and amastigote nest quantification. To further explain the in vitro antagonism, we explored whether pentamidine affects intracellular trypanothione levels, however, pentamidine produced no change in trypanothione concentrations. Finally, the T. cruzi polyamine permease (TcPAT12) was overexpressed in epimastigotes, showing that pentamidine has the same trypanocidal effect, independently of transporter expression levels. These results suggest that, in spite of the high potency in the putrescine transport blockade, TcPAT12 permease is not the main target of pentamidine, and could explain the lack of synergism between pentamidine and benznidazole.

Sex differences in endovascular thrombectomy outcomes in large vessel occlusion: a propensity-matched analysis from the SELECT study.

BACKGROUND: Sex disparities in acute ischemic stroke outcomes are well reported with IV thrombolysis. Despite several studies, there is still a lack of consensus on whether endovascular thrombectomy (EVT) outcomes differ between men and women. OBJECTIVE: To compare sex differences in EVT outcomes at 90-day follow-up and assess whether progression in functional status from discharge to 90-day follow-up differs between men and women. METHODS: From the Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) prospective cohort study (2016-2018), adult men and women (≥18 years) with anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1/M2) treated with EVT up to 24 hours from last known well were matched using propensity scores. Discharge and 90-day modified Rankin Scale (mRS) scores were compared between men and women. Furthermore, we evaluated the improvement in mRS scores from discharge to 90 days in men and women using a repeated-measures, mixed-effects regression model. RESULTS: Of 285 patients, 139 (48.8%) were women. Women were older with median (IQR) age 69 (57-81) years vs 64.5 (56-75), p=0.044, had smaller median perfusion deficits (Tmax >6 s) 109 vs 154 mL (p<0.001), and had better collaterals on CT angiography and CT perfusion but similar ischemic core size (relative cerebral blood flow <30%: 7.6 (0-25.2) vs 11.4 (0-38) mL, p=0.22). In 65 propensity-matched pairs, despite similar discharge functional independence rates (women: 42% vs men: 48%, aOR=0.55, 95% CI 0.18 to 1.69, p=0.30), women exhibited worse 90-day functional independence rates (women: 46% vs men: 60%, aOR=0.41, 95% CI 0.16 to 1.00, p=0.05). The reduction in mRS scores from discharge to 90 days also demonstrated a significantly larger improvement in men (discharge 2.49 and 90 days 1.88, improvement 0.61) than in women (discharge 2.52 and 90 days 2.44, improvement 0.08, p=0.036). CONCLUSION: In a propensity-matched cohort from the SELECT study, women had similar discharge outcomes as men following EVT, but the improvement from discharge to 90 days was significantly worse in women, suggesting the influence of post-discharge factors. Further exploration of this phenomenon to identify target interventions is warranted. TRIAL REGISTRATION NUMBER: NCT02446587.

GoCC4All a pervasive technology to provide access to TV to the deafblind community.

Considering the importance of communication and independence for the deafblind community, this work presents findings of the use of technology to address the lack of information due to communication challenges among the deafblind community. Over time, many investigations have been carried out regarding this matter, but very few providing solution, which is why this study emerged, looking to making all the information broadcasted through television accessible for this community. The work team designed a technology (GoCC4All) to address the needs of the deafblind community. GoCC4All provides access to captions available on TV through braille displays and mobile devices. Our research process and results outline the path for creating, adapting, and adopting new technologies for people with disabilities who have the right to access the information just as their peers without disabilities. The information in this paper is based on two surveys, an initial beta testing (BT) and a final survey among a group of 14 users (UT) who tested the GoCC4All application. Our findings support the positive impact of the iterative creation of assistive technology based on users' experience and users' recommendations to better serve the needs of the deafblind community.

Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi.

Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and African trypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect of pentamidine in Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have shown that pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its might also block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescine de novo, the inhibition of polyamine transport can bring a new therapeutic target against the parasite. In this work, we show that pentamidine decreases, not only the viability of T. cruzi trypomastigotes, but also the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflammation and parasite burden in hearts from infected mice. The treatment also decreases parasitemia, resulting in an increased survival rate. In addition, pentamidine strongly inhibits the putrescine and spermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate the utility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of new therapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to a well-known clinical profile, which could be an advantage over newly synthesized molecules that require more comprehensive trials prior to their clinical use.

The role of Gliadel wafers in the treatment of high-grade gliomas.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Standard treatment includes surgery, radiation and chemotherapy. Prognosis is dismal with an average survival of approximately 1 year. Gliadel wafers are one treatment option, working as a source for local chemotherapy delivery. Their use is controversial with questionable survival benefit and potential side effects. We reviewed the literature in an effort to clarify their role in the treatment of high-grade gliomas. A systematic PubMed search was performed using the keywords 'Gliadel', 'carmustine' or 'BCNU wafers' in newly diagnosed high-grade glioma patients. Treatment regimen, and median survival were analyzed. Adverse event ratio was calculated by computing the number of adverse events in a study per patient receiving carmustine wafers. Nineteen studies with 795 patients were included in our review. Survival was 8.7-22.6 months with a mean overall survival (OS) of 16.2 months (control survival is approximately 14 months with surgery and adjuvant chemoradiotherapy). Adverse event ratio using Gliadel wafersin control group. Complication rate was 42.7%. Gliadel wafers may marginally increase survival and local control in newly diagnosed GBM patients but are associated with a high complication rate; therefore, we do not recommend using Gliadel wafers in patients with GBM. Further research may be warranted once a safer alternative to Gliadel wafers has been introduced.