Analysis of the changes in the management of preterm newborns born in a Spanish third-level hospital in the past 10 years.

BACKGROUND: Preterm newborns require the use of the best and most current strategies to treat and prevent both acute pathology and associated sequelae. This study aimed to compare the differences in the management of preterm newborns over 10 years in a tertiary hospital in Spain and its impact on height, weight, and neurological development in the medium term. METHODS: We conducted a retrospective, observational, and analytical study examining the management and clinical variables in preterm newborns under 32 weeks of gestational age who were born in our hospital in 2011 and 2021. RESULTS: Twenty-six newborns were included in the study. Significant differences in magnesium sulfate use, continuous positive airway pressure immediately after birth, and non-invasive mechanical ventilation during hospitalization were observed. Differences were found in the use of parenteral nutrition and the timing of initiation of enteral feeding. We did not observe differences in the neurological or weight evolution in the medium term. CONCLUSIONS: Significant differences in managing preterm newborns in these 10 years were observed. Lower mortality and alterations in central nervous system ultrasound and, significantly, less growth retardation during admission in 2021 have been observed; however, it does not manifest with improvement in long-term somatometrics or neurological prognosis.

INTRODUCCIÓN: La inmadurez de los recién nacidos pretérmino (RNP) requiere el empleo de las mejores y más actuales estrategias para tratar la patología aguda y prevenir sus eventuales secuelas asociadas. El objetivo planteado es comparar las diferencias en el manejo de RNP a lo largo de diez años en un hospital de tercer nivel en España y su impacto en el desarrollo neurológico y póndero-estatural a medio plazo. MÉTODOS: Estudio retrospectivo, observacional y analítico examinando variables del manejo y clínicas de todos los RNP menores de 32 semanas de edad gestacional nacidos en nuestro hospital (nivel III-A) en 2011 y en 2021. RESULTADOS: Se incluyeron 26 infantes (2011: 10 niños, 2021: 16 niños). Observamos diferencias significativas en el uso prenatal de sulfato de magnesio, mayor uso de presión positiva continua en la vía aérea (CPAP) al ingreso y ventilación mecánica no invasiva durante el ingreso, retraso en el uso de surfactante, empleo de alimentación intravenosa e inicio precoz de la alimentación enteral. Existe una menor tasa de mortalidad y desnutrición postnatal en 2021. No observamos diferencias en la evolución neurológica o ponderal a medio plazo. CONCLUSIONES: Existen diferencias en el manejo de los prematuros en estos 10 años con mayor ajuste a las guías nacionales e internacionales vigentes. Esto se relaciona con menor mortalidad y alteraciones en la ecografía del sistema nervioso central y, significativamente, con un menor retraso en el crecimiento durante el ingreso en 2021; no se demostró mejoría del pronóstico somatométrico o neurológico a largo plazo.

2022 Polio outbreak, Rockland County, NY: Cost evaluation of strategies to prevent future outbreaks of vaccine-preventable diseases.

In 1994, the World Health Organization Region of the Americas was declared polio-free. In July 2022, a confirmed case of paralytic polio in an unvaccinated adult resident of Rockland County, New York was reported by the New York State Department of Health (NYSDOH) and Rockland County Department of Health (RCDOH). While only one case was identified, a single case of paralytic polio represents a public health emergency in the United States. The patient's county of residence was identified to have low vaccination coverage indicating that the community was at risk for additional cases. Disease outbreaks are resource-intensive and incur high costs to the patient, local health departments, and to society. These costs are potentially avoidable for vaccine-preventable diseases and thus, highlight the urgency to not only interrupt transmission but to prevent future vaccine-preventable disease outbreaks by improving vaccination coverage. Following case confirmation, an investigation and response was initiated by NYSDOH, along with local health departments and the Centers for Disease Control and Prevention (CDC). After the initial investigation and response, collaborative efforts to mitigate risk and strengthen routine immunization continued, which included provider outreach and immunization record assessments of Head Start and licensed childcare facilities (primarily those with missing or incomplete required vaccination coverage reports from the previous year) in Rockland County. We estimated the costs of (1) provider outreach and (2) childcare and pre-kindergarten immunization record assessments of select licensed childcare and Head Start facilities in Rockland County. The total labor cost incurred for these activities was $138,514 with a total of 2,555 h incurred. Often there are unique opportunities in the midst of an outbreak for public health to implement activities to proactively address low vaccination and strengthen vaccination coverage and possibly prevent future outbreaks. Understanding the cost of these activities might help inform future outbreak planning.

Perfil das infecções relacionadas à assistência à saúde na unidade de terapia intensiva de um hospital de referência na mesorregião oeste do Rio Grande do Norte / Profile of health care-related infections in the intensive care unit of a reference hospital in the west mesoregion of Rio Grande do Norte / Perfil de las infecciones relacionadas con la atención a la salud en la unidad de cuidados intensivos de un hospital de referencia en la mesoregión oeste del Rio Grande del Norte

As Infecções Relacionadas à Assistência à Saúde (IRAS) ocorrem com mais frequência em Unidade de Terapia Intensiva (UTI) devido a exposição maior dos pacientes a procedimentos e dispositivos invasivos, quadro clínico debilitado e sua manipulação pela equipe assistencial exigindo uso elevado de antimicrobianos, o que pode promover um risco de desenvolvimento de resistência bacteriana a estes, cujas consequências podem ser a dificuldade de tratamento, internamento prolongado, risco de óbito e maior custo associado. Tem como objetivo descrever as IRAs relacionando os agentes etiológicos e o tratamento antimicrobiano em uma UTI de um hospital de referência da mesorregião do Rio Grande do Norte. Trata-se de um estudo descritivo, retrospectivo e transversal de abordagem quantitativa. Foram inseridos 1.682 pacientes internados na UTI geral do hospital estudado entre 2017-2020. Os dados foram coletados a partir de fichas de registro que foram tabuladas e analisadas nos softwares Microsoft Office Excel® e Statistical Package for the Social Sciences utilizando estatística descritiva simples com apresentação de frequências, tendências e dispersão. A análise dos resultados revelou mediana de idade de 57 anos, prevalência do sexo masculino e existência de comorbidades em 57,9% dos casos, especialmente infecção prévia a admissão na UTI. O tempo médio de permanência na UTI foi 11,4 dias e taxa de mortalidade de 52%. Quanto aos dispositivos invasivos, observou-se uso de sonda vesical de demora (96,8%), ventilação mecânica (79,4%) e cateter venoso central (83,7%). Constatou-se 790 IRAS da UTI com crescimento bacteriano em 48,2%. As principais densidades de incidência (DI) de IRAS/1.000 pacientes-dia foram: IPCSL-CVC 1,8; PAV 27 e ITU-AC 22,3. Quanto aos antibióticos, observou-se Lenght of therapy de 872,5/1.000 pacientes-dia, sendo os mais prescritos: vancomicina (N=633), meropenem (N=625), ceftriaxona (N=479), amicacina (N=463) e polimixina B (N=448). Os valores destaques de Days of therapy/1.000 pacientes-dia: meropenem (N=305,7), amicacina (N=260,4), polimixina B (N=256,4), vancomicina (N=229,3) e imipenem (N=165,3). As bactérias mais isoladas nas culturas foram: Acinetobacter spp., Pseudomonas spp. e Klebsiella spp., as quais apresentaram resistência, principalmente, a: ceftazidima (51,5% - 87,3%); cefepima (61,6% - 85,3%); ciprofloxacino (56% - 84,6%) e meropenem (31,7% - 80,3%). Identificou-se não conformidades no tratamento com antibióticos em 455 pacientes, que envolvem principalmente polimixina B, vancomicina, meropenem e ceftriaxona. Conclui-se que há elevados níveis de tempo de permanência na UTI e uso de dispositivos invasivos, assim como DI de IRAS alta com identificação microbiológica de bactérias importantes, especialmente por seu perfil de resistência acentuado com destaque para antibióticos da classe dos carbapenêmicos e cefalosporinas de 3a e 4a geração. Destaca-se também a presença de não conformidades na administração de antibióticos que podem contribuir para a seleção de bactérias multirresistentes.

Health Care-Related Infections (HAI) occur more frequently in the Intensive Care Unit (ICU) due to the greater exposure of patients to invasive procedures and devices, weakened clinical status and their handling by the care team, requiring high use of antimicrobials, which can promote a risk of developing bacterial resistance to these, whose consequences may be difficult treatment, prolonged hospitalization, risk of death and higher associated costs. It aims to describe the IRAS relating the etiological agents and antimicrobial treatment in an ICU of a reference hospital in the mesoregion of Rio Grande do Norte. This is a descriptive, retrospective and cross-sectional study with a quantitative approach. A total of 1,682 patients admitted to the general ICU of the hospital studied between 2017-2020 were included. Data were collected from registration forms that were tabulated and analyzed in Microsoft Office Excel® and Statistical Package for the Social Sciences software using simple descriptive statistics with presentation of frequencies, trends and dispersion. The analysis of the results revealed a median age of 57 years, prevalence of males and the existence of comorbidities in 57.9% of cases, especially infection prior to admission to the ICU. The average length of stay in the ICU was 11.4 days and the mortality rate was 52%. As for invasive devices, the use of an indwelling urinary catheter (96.8%), mechanical ventilation (79.4%) and central venous catheter (83.7%) was observed. There were 790 IRAS in the ICU with bacterial growth in 21.67%. The main HAI incidence densities (DI)/1,000 patient-days were: IPCSL-CVC 1.8; PAV 27 and UTI-AC 22.3. As for antibiotics, a Length of therapy of 872.5/1,000 patient-days was observed, with the most prescribed being: vancomycin (N=633), meropenem (N=625), ceftriaxone (N=479), amikacin (N= 463) and polymyxin B (N=448). The highlighted values of Days of therapy/1000 patient-days: meropenem (N=305.7), amikacin (N=260.4), polymyxin B (N=256.4), vancomycin (N=229.3) and imipenem (N=165.3). The most isolated bacteria in cultures were: Acinetobacter spp., Pseudomonas spp. and Klebsiella spp., which showed resistance mainly to: Ceftazidime (51.5% - 87.3%); cefepime (61.6% - 85.3%); ciprofloxacin (56% - 84.6%) and meropenem (31.7% - 80.3%). Non-compliance was identified in the treatment with antibiotics in 455 patients, which mainly involve polymyxin B, vancomycin, meropenem and ceftriaxone. It is concluded that there are high levels of ICU length of stay and use of invasive devices, as well as high IRAS ID with microbiological identification of important bacteria, especially due to their accentuated resistance profile, with emphasis on antibiotics from the carbapenem class and cephalosporins from 3rd and 4th generation. Also noteworthy is the presence of non-compliance in the administration of antibiotics that may contribute to the selection of multidrug-resistant bacteria.

Las Infecciones Relacionadas con la Atención de la Salud (IRAS) ocurren con mayor frecuencia en la Unidad de Cuidados Intensivos (UCI) debido a la mayor exposición de los pacientes a procedimientos y dispositivos invasivos, el debilitamiento del estado clínico y su manejo por parte del equipo asistencial, requiriendo un alto uso de antimicrobianos , lo que puede promover un riesgo de desarrollar resistencia bacteriana a estos, cuyas consecuencias pueden ser un tratamiento difícil, hospitalización prolongada, riesgo de muerte y mayores costos asociados. Tiene como objetivo describir las IRAs que relacionan los agentes etiológicos y el tratamiento antimicrobiano en una UTI de un hospital de referencia en la mesorregión de Rio Grande do Norte. Se trata de un estudio descriptivo, retrospectivo y transversal con enfoque cuantitativo. Se incluyeron un total de 1.682 pacientes ingresados en la UCI general del hospital estudiado entre 2017-2020. Los datos fueron recolectados a partir de formularios de registro que fueron tabulados y analizados en el software Microsoft Office Excel® y Statistical Package for the Social Sciences utilizando estadística descriptiva simple con presentación de frecuencias, tendencias y dispersión. El análisis de los resultados reveló una mediana de edad de 57 años, predominio del sexo masculino y la existencia de comorbilidades en el 57,9% de los casos, especialmente infección previa al ingreso en UCI. La estancia media en la UCI fue de 11,4 días y la tasa de mortalidad fue del 52%. En cuanto a los dispositivos invasivos, se observó el uso de catéter urinario permanente (96,8%), ventilación mecánica (79,4%) y catéter venoso central (83,7%). Había 790 IRAS en la UCI con crecimiento bacteriano en el 48,2%. Las principales densidades de incidencia (DI) de IRAS/1.000 pacientes-día fueron: IPCSL-CVC 1,8; PAV 27 y UTI-AC 22.3. En cuanto a los antibióticos, se observó una Duración de la terapia de 872,5/1.000 días-paciente, siendo los más prescritos: vancomicina (N=633), meropenem (N=625), ceftriaxona (N=479), amikacina (N= 463) y polimixina B (N=448). Los valores destacados de Días de terapia/1.000 pacientes-día: meropenem (N=305,7), amikacina (N=260,4), polimixina B (N=256,4), vancomicina (N=229,3) e imipenem (N=165,3). Las bacterias más aisladas en cultivos fueron: Acinetobacter spp., Pseudomonas spp. y Klebsiella spp., que mostraron resistencia principalmente a: ceftazidima (51,5% - 87,3%); cefepima (61,6% - 85,3%); ciprofloxacino (56% - 84,6%) y meropenem (31,7% - 80,3%). Se identificó incumplimiento en el tratamiento con antibióticos en 455 pacientes, los cuales involucran principalmente polimixina B, vancomicina, meropenem y ceftriaxona. Se concluye que existen altos índices de estancia en UCI y uso de dispositivos invasivos, así como elevado IRAS ID con identificación microbiológica de bacterias importantes, especialmente por su acentuado perfil de resistencia, con énfasis en antibióticos de la clase carbapenémicos y cefalosporinas de 3ra y 4ta generación. También es destacable la presencia de incumplimiento en la administración de antibióticos que pueden contribuir a la selección de bacterias multirresistentes.

Antiparasitic Activity of Compounds Isolated from Ganoderma tuberculosum (Agaricomycetes) from Mexico.

The genus Ganoderma has a long history of use in traditional Asiatic medicine due to its different nutritional and medicinal properties. In Mexico, the species G. tuberculosum is used in indigenous communities, for example, the Wixaritari and mestizos of Villa Guerrero Jalisco for the treatment of diseases that may be related to parasitic infections; however, few chemical studies corroborate its traditional medicinal potential. Thereby, the objective of this study was to isolate and identify anti-parasitic activity compounds from a strain of G. tuberculosum native to Mexico. From the fruiting bodies of G. tuberculosum (GVL-21) a hexane extract was obtained which was subjected to guided fractioning to isolate pure compounds. The in vitro anti-parasitic activity of the pure compound (IC50) was assayed against Leishmania amazonensis, Trypanosoma cruzi, Acanthamoeba castellanii Neff, and Naegleria fowleri. Furthermore, the cytotoxicity (CC50) of the isolated compounds was determined against murine macrophages. The guided fractioning produced 5 compounds: ergosterol (1), ergosta-4,6,8(14),22-tetraen-3-one (2), ergosta-7,22-dien-3ß-ol (3), 3,5-dihydroxy-ergosta-7,22-dien-6-one (4), and ganoderic acid DM (5). Compounds 2 and 5 showed the best anti-parasitic activity in an IC50 range of 54.34 ± 8.02 to 12.38 ± 2.72 µM against all the parasites assayed and low cytotoxicity against murine macrophages. The present study showed for the first time the in vitro anti-parasitic activity of compounds 1-5 against L. amazonensis, T. cruzi, A. castellanii Neff, and N. fowleri, corroborating the medicinal potential of Ganoderma and its traditional applications.

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.

Efficacy of mouthrinses in reducing oral SARS-COV-2 load: a review.

Accumulated evidence has shown that the oral cavity may be an important reservoir for SARS-CoV-2. Some authors have suggested that the use of mouthrinses could reduce SARS-CoV-2 viral load in the saliva. Thus, the aim of this review was to synthesize evidence about the efficacy of mouthrinses in reducing the salivary viral load of SARS-CoV-2. 2. Nine randomized controlled trials (RCTs) have investigated the efficacy of different mouthrinses in reducing salivary SARS-CoV-2 loads. Various active ingredients have been tested in these trials: 0.5%,1% and 2% povidone-iodine, 0.2% and 0.12% chlorhexidine (CHX), 0.075% cetylpyridinium chloride (CPC), 0.075% CPC with Zinc lactate, 1% and 1.5% hydrogen peroxide (HP), 1.5% HP + 0.12% CHX and ß-cyclodextrin and citrox. The studies reported an intra-group reduction in the salivary levels of the virus, when compared with the baseline. However, the majority of these trials failed to demonstrate a significant inter-group difference between active groups and the control group relative to the decrease in salivary SARS-CoV-2 loads. Although promising, these results should be confirmed by larger trials.

Efficacy of mouthrinses in reducing oral SARS-COV-2 load: a review

Abstract Accumulated evidence has shown that the oral cavity may be an important reservoir for SARS-CoV-2. Some authors have suggested that the use of mouthrinses could reduce SARS-CoV-2 viral load in the saliva. Thus, the aim of this review was to synthesize evidence about the efficacy of mouthrinses in reducing the salivary viral load of SARS-CoV-2. 2. Nine randomized controlled trials (RCTs) have investigated the efficacy of different mouthrinses in reducing salivary SARS-CoV-2 loads. Various active ingredients have been tested in these trials: 0.5%,1% and 2% povidone-iodine, 0.2% and 0.12% chlorhexidine (CHX), 0.075% cetylpyridinium chloride (CPC), 0.075% CPC with Zinc lactate, 1% and 1.5% hydrogen peroxide (HP), 1.5% HP + 0.12% CHX and ß-cyclodextrin and citrox. The studies reported an intra-group reduction in the salivary levels of the virus, when compared with the baseline. However, the majority of these trials failed to demonstrate a significant inter-group difference between active groups and the control group relative to the decrease in salivary SARS-CoV-2 loads. Although promising, these results should be confirmed by larger trials.

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.

Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri.

Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future.

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.

Antikinetoplastid Activity of Sesquiterpenes Isolated from the Zoanthid Palythoa aff. clavata.

Leishmaniasis and Chagas disease are neglected tropical diseases that cause problems in developing countries. The causative agents, Leishmania spp. and Trypanosoma cruzi, produce a clinical picture that can be fatal for the patient, such as Chagas heart disease, visceral leishmaniasis and megacolon, among others. Current treatments for these diseases are not very effective and highly toxic, since they require very prolonged treatments. The development of innovative, effective and safe drugs to fight infections caused by these parasites remains a challenge. For this reason, in recent years, there has been an increase in the search for new therapies. In this study, the antikinetoplastid activity of 13 sesquiterpene lactones obtained from Palythoa aff. clavata was screened against L. amazonensis, L. donovani and T. cruzi. The results revealed that the sesquiterpene lactones anhydroartemorin (2), cis,trans-costunolide-14-acetate (3) and 4-hydroxyarbusculin A (11) were the most selective against the kinetoplastid species studied. These molecules seem to induce the mechanisms involved in an apoptotic-like death or programmed cell death (PCD) in the kinetoplastids, and since they do not cause necrosis, the inflammatory events associated with this type of cell death will not be triggered.

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.

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.

Contribuições de Agentes Comunitários de Saúde para a construção do perfil de usuários da Atenção Básica com necessidades de saúde mental / Community Health Agents contributions to set up the profile of Primary Care Services users with mental health demands

Resumo Introdução A Atenção Básica à Saúde, que integra a Rede de Atenção Psicossocial (RAPS), deve apresentar papel fundamental para a identificação de casos, acompanhamento e promoção da saúde mental, ações com as quais os Agentes Comunitários de Saúde (ACS) podem contribuir. Objetivo Analisar a situação de saúde mental do município de Itabuna-BA, comparando informações fornecidas por ACS e pelo Sistema de Informação em Saúde para a Atenção Básica (SISAB). Método Trata-se de pesquisa exploratória, descritiva, documental, que recuperou informações do SISAB e de Fichas de Cadastro da Coordenação de Saúde Mental, preenchidas por ACS. Resultados A participação dos ACS elevou em mais de seis vezes o número de pessoas com transtornos mentais identificadas, mas o número de usuários de álcool e outras substâncias foi inferior ao registrado no SISAB. Foram constatadas evidências de desarticulação da RAPS e modelo de atenção biologizante e hospitalocêntrico. Conclusão As fontes de informação se complementaram, evidenciando subnotificação dos casos de saúde mental e bom potencial dos ACS para auxiliar na busca ativa de usuários com transtorno mental, mas não de usuários de substâncias. Problemas de saúde mental relacionaram-se com aspectos de vulnerabilidade socioeconômica, indicando a necessidade de articulação intersetorial para oferecer atenção integral à saúde.

ABSTRACT Background Primary Care Services is part of the Brazilian Psychosocial Care Network (PCN) and is expected to play a fundamental role in the identification of cases, monitoring and promotion of mental health, to which Community Health Agents (CHA) can contribute. Objective Analyze the mental health situation of the municipality of Itabuna - BA, compare information provided by CHAs and the Health Information System for Primary Care (SISAB). Method This was an exploratory, descriptive, documentary research that retrieved information from the SISAB and from Mental Health Coordination registry files, completed by CHAs. Results The participation of CHAs increased by more than six times the number of people with mental disorders identified, but the number of users of alcohol and other drugs was lower than that registered in SISAB. Conclusion There was evidence of PCN disarticulation and a model of biological and hospital-centered care. The sources of information complemented each other, evidencing underreport of mental health cases and good potential for CHAs assistance in the active search of users with mental disorders, but not of drug users. Mental health problems were related to aspects of socioeconomic vulnerability, indicating the need for intersectoral articulation to provide comprehensive health care.