Poliovirus outbreak in New York State, August 2022: qualitative assessment of immediate public health responses and priorities for improving vaccine coverage.

In 2022, a case of paralysis was reported in an unvaccinated adult in Rockland County (RC), New York. Genetically linked detections of vaccine-derived poliovirus type 2 (VDPV2) were reported in multiple New York counties, England, Israel, and Canada. The aims of this qualitative study were to: i) review immediate public health responses in New York to assess the challenges in addressing gaps in vaccination coverage; ii) inform a longer-term strategy to improving vaccination coverage in under-vaccinated communities, and iii) collect data to support comparative evaluations of transnational poliovirus outbreaks. Twenty-three semi-structured interviews were conducted with public health professionals, healthcare professionals, and community partners. Results indicate that i) addressing suboptimal vaccination coverage in RC remains a significant challenge after recent disease outbreaks; ii) the poliovirus outbreak was not unexpected and effort should be invested to engage mothers, the key decision-makers on childhood vaccination; iii) healthcare providers (especially paediatricians) received technical support during the outbreak, and may require resources and guidance to effectively contribute to longer-term vaccine engagement strategies; vi) data systems strengthening is required to help track under-vaccinated children. Public health departments should prioritize long-term investments in appropriate communication strategies, countering misinformation, and promoting the importance of the routine immunization schedule.

Rapid Screening of Polyol Polyketides from Marine Dinoflagellates.

Dinoflagellate-derived polyketides are typically large molecules (>1000 Da) with complex structures, potent bioactivities, and high toxicities. Their discovery suffers three major bottlenecks: insufficient bioavailability, low-yield cultivation of producer organisms, and production of multiple highly related analogues by a single strain. Consequently, the biotechnological production of therapeutics or toxicological standards of dinoflagellate-derived polyketides is also hampered. Strategies based on sensitive and selective techniques for chemical prospection of dinoflagellate extracts could aid in overcoming these limitations, as it allows selecting the most interesting candidates for discovery and exploitation programs according to the biosynthetic potential. In this work, we assess the combination of data-dependent liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS2) and molecular networking to screen polyol polyketides. To demonstrate the power of this approach, we selected dinoflagellate Amphidinium carterae since it is commonly used as a biotechnological model and produces amphidinols, a family of polyol-polyene compounds with antifungal and antimycoplasmal activity. First, we screened families of compounds with multiple hydroxyl groups by examining MS2 profiles that contain sequential neutral losses of water. Then, we clustered MS2 spectra by molecular networking to facilitate the dereplication and discovery of amphidinols. Finally, we used the MS2 fragmentation behavior of well-characterized luteophanol D as a model to propose a structural hypothesis of nine novel amphidinols. We envision that this strategy is a valuable approach to rapidly monitoring toxin production of known and unknown polyol polyketides in dinoflagellates, even in small culture volumes, and distinguishing strains according to their toxin profiles.

Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater - New York, June-August 2022.

On July 18, 2022, the New York State Department of Health (NYSDOH) notified CDC of detection of poliovirus type 2 in stool specimens from an unvaccinated immunocompetent young adult from Rockland County, New York, who was experiencing acute flaccid weakness. The patient initially experienced fever, neck stiffness, gastrointestinal symptoms, and limb weakness. The patient was hospitalized with possible acute flaccid myelitis (AFM). Vaccine-derived poliovirus type 2 (VDPV2) was detected in stool specimens obtained on days 11 and 12 after initial symptom onset. To date, related Sabin-like type 2 polioviruses have been detected in wastewater* in the patient's county of residence and in neighboring Orange County up to 25 days before (from samples originally collected for SARS-CoV-2 wastewater monitoring) and 41 days after the patient's symptom onset. The last U.S. case of polio caused by wild poliovirus occurred in 1979, and the World Health Organization Region of the Americas was declared polio-free in 1994. This report describes the second identification of community transmission of poliovirus in the United States since 1979; the previous instance, in 2005, was a type 1 VDPV (1). The occurrence of this case, combined with the identification of poliovirus in wastewater in neighboring Orange County, underscores the importance of maintaining high vaccination coverage to prevent paralytic polio in persons of all ages.

Adverse events of metronidazole and amoxicillin: Retrospective analysis of a large data set of five randomized clinical trials.

AIM: To evaluate the frequency of side effects associated with intake of metronidazole (MTZ) + amoxicillin (AMX) in periodontal treatment, and to explore associations between these events and patients' features. MATERIALS AND METHODS: Data of five randomized clinical trials testing MTZ + AMX adjunctive to mechanical therapy were evaluated. Volunteers answered an adverse event questionnaire. RESULTS: Information from 656 subjects was assessed. The frequency of side effects in the antibiotic- and placebo-treated groups ranged from 1.0% to 17.7% and 0.9% to 13.7%, respectively. The events more frequently observed in the antibiotic than in the placebo group were diarrhoea and metallic taste (p < .05). Diabetes significantly raised the odds of a patient reporting discomfort (odds ratio [OR] = 2.6), diarrhoea (OR = 4.0), weakness (OR = 6.0) and excessive sleepiness (OR = 2.9). In systemically healthy volunteers, using antibiotics 3 months post-mechanical treatment (healing phase) (OR = 3.0), being a woman (OR = 3.9) and aged ≤49 (OR = 4.5) significantly increased the chances of reporting adverse events. CONCLUSIONS: The occurrence of side effects during MTZ + AMX treatment ranged from uncommon (1%) to very common (17.7%). The main factors raising the chances of a patient reporting adverse events were diabetes and taking antibiotics in the healing phase, instead of in the active phase of treatment. Patients ≤ 49 years old and females also tend to report more side effects.

Pacemaker lead-related macroreentrant atrial tachycardia.

Macroreentrant atrial circuits are frequently associated with scarring. Previous reports have shown the possible development of scar tissue that is adjacent to pacemaker (PM) leads. However, reports of PM lead-related reentrant tachycardia are scarce. We report the case of a 63-year-old woman who presented with macroreentrant atrial tachycardia (MAT), related to the atrial trajectory of an old single-lead ventricular PM, that was successfully treated with radiofrequency ablation after a conventional electrophysiological study ruled out isthmus-dependent atrial flutter and provided sufficient data to confirm this diagnosis. This report presents a case of MAT originating around the trajectory of a PM lead, probably because of scar tissue that developed adjacent to the lead. Experimental studies have already shown that interstitial atrial fibrosis may develop adjacent to a ventricular single-lead. This finding suggests that MAT develops in patients with this specific condition. Recognizing this condition is important for managing these arrhythmias and performing safe ablation with the preservation of PM lead integrity.

Antiamoebic effects of sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata.

Opportunistic parasitic protozoa of genus Acanthamoeba are responsible to cause severe infections in humans such as Acanthamoeba Keratitis or Amoebic Granulomatous Encephalitis. Current treatments are usually toxic and inefficient and there is a need to access new therapeutic agents. The antiamoebic effects of nephthediol (1) and fourteen germacranolide and eudesmanolide sesquiterpene lactones (2-5, 7-12) isolated from the indigenous zoanthid Palythoa aff. clavata collected at the coast of Lanzarote, Canary Islands were studied against Acanthamoeba castellanii Neff, and the clinical strains A. polyphaga and A. griffini. 4-epi-arbusculin A (11) presented the lowest IC50 value (26,47 ± 1,69 µM) against A. castellanii Neff and low cytotoxicity against murine macrophages, followed by isobadgerin (2), which also showed to be active against A. castellanii Neff cysts. The studies on the mode of action of compounds 2 and 11 revealed these sesquiterpene lactones induce mechanisms of PDC on A. castellanii Neff.

Isolation and Structural Elucidation of New Amphidinol Analogues from Amphidinium carterae Cultivated in a Pilot-Scale Photobioreactor.

The demand for valuable products from dinoflagellate biotechnology has increased remarkably in recent years due to their many prospective applications. However, there remain many challenges that need to be addressed in order to make dinoflagellate bioactives a commercial reality. In this article, we describe the technical feasibility of producing and recovering amphidinol analogues (AMs) excreted into a culture broth of Amphidinium carterae ACRN03, successfully cultured in an LED-illuminated pilot-scale (80 L) bubble column photobioreactor operated in fed-batch mode with a pulse feeding strategy. We report on the isolation of new structurally related AMs, amphidinol 24 (1, AM24), amphidinol 25 (2, AM25) and amphidinol 26 (3, AM26), from a singular fraction resulting from the downstream processing. Their planar structures were elucidated by extensive NMR and HRMS analysis, whereas the relative configuration of the C-32→C-47 bis-tetrahydropyran core was confirmed to be antipodal in accord with the recently revised configuration of AM3. The hemolytic activities of the new metabolites and other related derivatives were evaluated, and structure-activity conclusions were established. Their isolation was based on a straightforward and high-performance bioprocess that could be suitable for the commercial development of AMs or other high-value compounds from shear sensitive dinoflagellates.

Smoking Cessation therapy is a cost-effective intervention to avoid tooth loss in Brazilian subjects with periodontitis: an economic evaluation.

BACKGROUND: Smokers present a higher prevalence and severity of periodontitis and, consequently, higher prevalence of tooth loss. Smoking cessation improves the response to periodontal treatment and reduces tooth loss. So, the aim of this study was to evaluate the efficiency in resources allocation when implementing smoking cessation therapy vs. its non-implementation in smokers with periodontitis. METHODS: We adopted the Brazilian public system perspective to determine the incremental cost-effectiveness (cost per tooth loss avoided) and cost-utility (cost per oral-related quality-adjusted life-year ([QALY] gained) of implementing smoking cessation therapy. Base-case was defined as a 48 years-old male subject and horizon of 30 years. Effects and costs were combined in a decision analytic modeling framework to permit a quantitative approach aiming to estimate the value of the consequences of smoking cessation therapy adjusted for their probability of occurrence. Markov models were carried over annual cycles. Sensitivity analysis tested methodological assumptions. RESULTS: Implementing the therapy saved approximately US$ 100 over the time horizon accompanied by a slightly better effect, both in CEA and CUA. Considering uncertainties, the therapy could be cost-effective in the most part of simulated cases, even being cheaper and more effective in 35% of cases in which the oral-health related outcome is used as effect. Considering a willingness-to-pay of US$100 per health effect, smoking cessation therapy was cost-effective, respectively, in 72% and 99% of cases in cost-utility and cost-effectiveness analyses. CONCLUSIONS: Implementation of smoking cessation therapy may be cost-effective, considering the avoidance of tooth loss and oral health-related consequences to patients.

Ultrasound-guided continuous block of median and ulnar nerves in horses: development of the technique.

OBJECTIVE: To develop a technique for ultrasound-guided continuous median and ulnar peripheral nerve block in horses. STUDY DESIGN: Anatomical and prospective experimental study. ANIMALS: A total of 16 thoracic limbs from horse cadavers and 18 adult horses. METHOD: This study was conducted in three phases. Phase 1: Dissection of median and ulnar nerves in the antebrachial region of two cadaver limbs to identify localizing landmarks. Description of sonoanatomy in 14 cadaver limbs using ultrasound-guided perineural infiltration of a combination of cellulose gel (5 mL), contrast medium (4 mL) and methylene blue (1 mL). Catheters were inserted between the perineural sheath and epineurium in six limbs, followed by computed tomography. Phase 2: Ultrasonographic images of the limbs of 18 healthy horses of different breeds were used to define an acoustic window and optimize the approach to nerves. Phase 3: Two case reports of horses with chronic pain of different etiologies. Catheters were inserted between the epineurium and paraneural sheath of the median and/or ulnar nerves guided by ultrasound, followed by continuous infusion of 0.4% ropivacaine. RESULTS: Information from phase 1 was used to direct needle insertion, solution dispersion and catheter implantation in phase 2, which resulted in 100% technique accuracy. In response to the peripheral nerve block, pain reduction was apparent in the two clinical cases by increased weight bearing in affected limbs and decreased requirement for systemic analgesic medications. No local reactions were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrasound technique allowed real-time visualization of needle, catheter and drug dispersion and resulted in a high success rate for nerve blocks. The horses administered a median and ulnar nerve block exhibited no discomfort or signs of infection at the catheter insertion site. Further studies are warranted to validate the efficacy of this technique.

Antiprotozoal activities of marine polyether triterpenoids.

Chagas disease and leishmaniasis are tropical neglected diseases caused by kinetoplastids protozoan parasites of Trypanosoma and Leishmania genera, and a public health burden with high morbidity and mortality rates in developing countries. Among difficulties with their epidemiological control, a major problem is their limited and toxic treatments to attend the affected populations; therefore, new therapies are needed in order to find new active molecules. In this work, sixteen Laurencia oxasqualenoid metabolites, natural compounds 1-11 and semisynthetic derivatives 12-16, were tested against Leishmania amazonensis, Leishmania donovani and Trypanosoma cruzi. The results obtained point out that eight substances possess potent activities, with IC50 values in the range of 5.40-46.45 µM. The antikinetoplastid action mode of the main metabolite dehydrothyrsiferol (1) was developed, also supported by AFM images. The semi-synthetic active compound 28-iodosaiyacenol B (15) showed an IC50 5.40 µM against Leishmania amazonensis, turned to be non-toxic against the murine macrophage cell line J774A.1 (CC50 > 100). These values are comparable with the reference compound miltefosine IC50 6.48 ±â€¯0.24 and CC50 72.19 ±â€¯3.06 µM, suggesting that this substance could be scaffold for development of new antikinetoplastid drugs.

Evaluation of Oxasqualenoids from the Red Alga Laurencia viridis against Acanthamoeba.

Acanthamoeba genus is a widely distributed and opportunistic parasite with increasing importance worldwide as an emerging pathogen in the past decades. This protozoan has an active trophozoite stage, a cyst stage, and is dormant and very resistant. It can cause Acanthamoeba keratitis, an ocular sight-threatening disease, and granulomatous amoebic encephalitis, a chronic, very fatal brain pathology. In this study, the amoebicidal activity of sixteen Laurencia oxasqualenoid metabolites and semisynthetic derivatives were tested against Acanthamoeba castellanii Neff. The results obtained point out that iubol (3) and dehydrothyrsiferol (1) possess potent activities, with IC50 values of 5.30 and 12.83 µM, respectively. The hydroxylated congeners thyrsiferol (2) and 22-hydroxydehydrothyrsiferol (4), active in the same value range at IC50 13.97 and 17.00 µM, are not toxic against murine macrophages; thus, they are solid candidates for the development of new amoebicidal therapies.

Effect of smoking cessation on tooth loss: a systematic review with meta-analysis.

BACKGROUND: Smoking is a major risk factor for periodontitis and tooth loss. Smoking cessation has a positive impact in periodontal treatment. However, so far, no systematic review has evaluated the effect of smoking cessation on tooth loss. Therefore, this review aimed to evaluate if smoking cessation reduces the risk of tooth loss. METHODS: Observational (cross-sectional and longitudinal) studies that investigated the association between smoking cessation and tooth loss were included. MEDLINE, EMBASE and LILACS databases were searched for articles published up to November 2018. Pooled results for subgroups of current and former smokers were compared in meta-analysis. Meta-regression was used to test the influence of smoking status on estimates and explore the heterogeneity. RESULTS: Of 230 potentially relevant publications, 21 studies were included in the qualitative review and 12 in the quantitative analysis. Meta-analysis of cross-sectional studies did not show any differences between former and current smokers in the chance of losing 1 or more teeth (OR = 1.00; 95% CI = 0.80 to 1.24, I2 = 80%), losing more than 8 teeth (OR = 1.02; 95% CI = 0.78 to 1.32, I2 = 0%) or being edentulous (OR = 1.37; 95% CI = 0.94 to 1.99, I2 = 98%). Meta-analysis from longitudinal studies showed that, when compared to never smokers, former smokers presented no increased risk of tooth loss (RR = 1.15; 95% CI = 0.98 to 1.35, I2 = 76%), while current smokers presented an increased risk of tooth loss (RR = 2.60; 95% CI = 2.29 to 2.96, I2 = 61%). Meta-regression showed that, among former smokers, the time of cessation was the variable that better explained heterogeneity (approximately 60%). CONCLUSIONS: Risk for tooth loss in former smokers is comparable to that of never smokers. Moreover, former smokers have a reduced risk of tooth loss, when compared to current smokers.

Catheter entrapment in Chiari network: Extraction with radiofrequency.

We report a challenging case of a duodecapolar mapping catheter entrapment in Chiari network and its release by radiofrequency energy application with an ablation catheter.

Marine Longilenes, Oxasqualenoids with Ser-Thr Protein Phosphatase 2A Inhibition Activity.

The red seaweed Laurencia viridis is a rich source of oxygenated secondary metabolites that were derived from squalene. We report here the structures of three novel compounds, (+)-longilene peroxide (1), longilene (2), and (+)-prelongilene (3) that were isolated from this alga, in addition to other substances, 4 and 5, resulting from their acid-mediated degradation. The effect of compounds 1 and 3 against Ser-Thr protein phosphatase type 2A (PP2A) was evaluated, showing that (+)-longilene peroxide (1) inhibited PP2A (IC50 11.3 μM). In order to explain the interaction between PP2A and compounds 1 and 3, molecular docking simulations onto the PP2A enzyme-binding region were used.

Marine Microalgae: Promising Source for New Bioactive Compounds.

The study of marine natural products for their bioactive potential has gained strength in recent years. Oceans harbor a vast variety of organisms that offer a biological and chemical diversity with metabolic abilities unrivalled in terrestrial systems, which makes them an attractive target for bioprospecting as an almost untapped resource of biotechnological applications. Among them, there is no doubt that microalgae could become genuine "cell factories" for the biological synthesis of bioactive substances. Thus, in the course of inter-laboratory collaboration sponsored by the European Union (7th FP) into the MAREX Project focused on the discovery of novel bioactive compounds of marine origin for the European industry, a bioprospecting study on 33 microalgae strains was carried out. The strains were cultured at laboratory scale. Two extracts were prepared for each one (biomass and cell free culture medium) and, thus, screened to provide information on the antimicrobial, the anti-proliferative, and the apoptotic potential of the studied extracts. The outcome of this study provides additional scientific data for the selection of Alexadrium tamarensis WE, Gambierdiscus australes, Prorocentrum arenarium, Prorocentrum hoffmannianum, and Prorocentrum reticulatum (Pr-3) for further investigation and offers support for the continued research of new potential drugs for human therapeutics from cultured microalgae.

Orthodontic treatment in patients with aggressive periodontitis.

INTRODUCTION: Aggressive periodontitis (AP) is a condition that promotes breakdown of the periodontal tissues in a short time. In severe cases, pathologic migration of teeth and tooth loss can occur, producing esthetic and functional problems for the patient. Orthodontic treatment may be recommended to restore esthetics and masticatory function. We assessed the effects of orthodontic movement in the periodontal tissues of treated patients with AP. METHODS: Ten subjects (ages 25.0 ± 5.22 years) with AP received periodontal treatment followed by orthodontic treatment. Maintenance sessions were performed monthly under a strict dental biofilm control. They were compared with 10 periodontally healthy subjects (ages 22.9 ± 5.23 years) who received orthodontic treatment. Probing pocket depth, clinical attachment level, bleeding on probing, and dental plaque index were measured at baseline, after orthodontic treatment, and after 4 months. RESULTS: Statistical analysis showed improvement in all clinical parameters between baseline and 4 months after orthodontic treatment: probing pocket depth (0.29 mm), clinical attachment level (0.38 mm), bleeding on probing (4.0%), and dental plaque index (11%). CONCLUSIONS: The periodontal parameters of the AP patients remained stable during orthodontic treatment under strict biofilm control.

Pinnatifidenyne-Derived Ethynyl Oxirane Acetogenins from Laurencia viridis.

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C15 acetogenin medium-ring ethers. Here, we described the isolation of three new C15 acetogenins (3-5), and one truncated derivative (6) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives (3-4). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J-based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated.

Additional Insights into the Obtusallene Family: Components of Laurencia marilzae.

The obtusallenes are a significant subset of C15-halogenated acetogenins that incorporate 12-membered cyclic ethers. We have recently reported the isolation from Laurencia marilzae of 12-epoxyobtusallene IV (1) and its related α,ß-unsaturated carboxylate ester (2), both of special biogenetic relevance. Here we describe the final step of our study, the isolation of three new analogues (3-5), among these, the first bromopropargylic derivative (3) of this class of macrocyclic C15-acetogenins. The structures were elucidated by analysis of NMR and X-ray data. 12-Epoxyobtusallene IV (1), its new isomer 4, and known obtusallene IV (6) were evaluated for their apoptosis-inducing activities in a human hepatocarcinoma cell line.