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Essential oils (EOs) are considered a new class of ecological products aimed at the control of insects for industrial and domestic use; however, there still is a lack of studies involving the control of fleas. Ctenocephalides felis felis, the most observed parasite in dogs and cats, is associated with several diseases. The aim of this study was to evaluate the in vitro activity, the establishment of LC50 and toxicity of EOs from Alpinia zerumbet (Pers.) B. L. Burtt & R. M. Sm, Cinnamomum spp., Laurus nobilis L., Mentha spicata L., Ocimum gratissimum L. and Cymbopogon nardus (L.) Rendle against immature stages and adults of C. felis felis. Bioassay results suggest that the method of evaluation was able to perform a pre-screening of the activity of several EOs, including the discriminatory evaluation of flea stages by their LC50. Ocimum gratissimum EO was the most effective in the in vitro assays against all flea stages, presenting adulticide (LC50 = 5.85 μg cm−2), ovicidal (LC50 = 1.79 μg cm−2) and larvicidal (LC50 = 1.21 μg cm−2) mortality at low doses. It also presented an excellent profile in a toxicological eukaryotic model. These findings may support studies involving the development of non-toxic products for the control of fleas in dogs and cats.
The purpose of this paper is to explore the connection between expressivism and disagreement. More in particular, the aim is to defend that one of the desiderata that can be derived from the study of disagreement, the explanation of ‘crossed disagreements’, can only be accommodated within a semantic theory that respects, at the meta-semantic level, certain expressivistic restrictions. We will compare contemporary dynamic expressivism with three different varieties of contextualist strategies to accommodate the specificities of evaluative language –indexical contextualism – truth-conditional pragmatics –, pragmatic strategies using implicatures, and presuppositional accounts. Our conclusion will be that certain assumptions of expressivism are necessary in order to provide a semantic account of evaluative uses of language that can allow us to detect and prevent crossed disagreements.
Cancer during pregnancy has an incidence of 1/1,000, and when diagnosed, the most common ones are breast cancer (1/10,000), Hodgkin’s lymphoma (1/6,000), and head and neck cancer (1/10,000). If a diagnosis is made during pregnancy, the treatment cannot wait until delivery, and there is concern about the effects that radiotherapy may have on the foetus. The multidisciplinary group has to assess and ethically make decisions with regard to the mother and foetus.
A 35-year-old female, a carrier of Behcet’s disease, underwent 5 years of treatment with hydroxychloroquine, prednisone and low-molecular-weight heparin (the patient being a carrier of Behcet’s disease, there is a high risk for cancer of the oral cavity and oropharynx with an HR of 2·11, so the cancer could be related to the tonsil). The patient’s oncological situation started on December 2017 with a volume increase in preauricular, parotid and right mandibular angle, with a progressive growth. At this time, the foetus was of 17·5 weeks of gestation. An oral cavity tumour that invaded the right retromolar triangle was observed, and upon biopsy, a basaloid squamous cell carcinoma was diagnosed.
Radiotherapy treatment was started at 22 weeks of gestation; intensity-modulated radiation therapy (IMRT) was planned with a dose of 69·96 Gy to the primary tumour and 59·4 Gy to ganglion levels II, III and IV, bilaterally in 33 fractions. At fraction 27 a significant decrease in tumour volume was noted, so adaptive radiotherapy was performed to complete the treatment. Currently the patient has no clinical evidence of tumour pathology.
The risk of radiation exposure in pregnant women (after 20 weeks of gestation), being treated for cancers of the tonsil, reaching the foetus is minimal, with a reduced risk of a few or no effects.
Radiotherapy in tonsil cancer has been shown to be effective in combination with chemotherapy for local control of the disease. In the case of this pregnant patient, radiotherapy, as the only modality, provided local control and little exposure of radiation to the foetus.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Pharmaceutical services for public health emergencies, such as the Zika virus (ZIKV) epidemic, are relevant for service effectiveness in the Brazilian health system. Pharmacists can act strategically in risk reduction. However, official guidelines do not consider pharmaceutical services when approaching health emergencies.
To identify and understand primary healthcare pharmacist interventions in risk reduction for the recent ZIKV epidemic in Brazil.
The study took place in Campo Grande, Mato Grosso do Sul, in November 2017. A semi-structured questionnaire was developed, including general issues related to knowledge of Zika, risk communication, and the pharmacist's role in patient care for ZIKV disease. The instrument was pre-tested. Primary healthcare center (PHC) pharmacists were subsequently interviewed. Aspects related to knowledge, risk reduction measures, and role were categorized and analyzed. The project received approval from the Institutional Review Board (IRB) at the Sergio Arouca National School of Public Health.
Forty-two of the 48 PHC pharmacists in Campo Grande were interviewed. Risk reduction measures were cited by most interviewees. Among these strategies, 92% were collective measures, such as making information available for the population (30%) and for the health workers (8%), and vector control strategies (43%). Use of mosquito nets was the most cited individual risk-reduction strategy. Only one pharmacist cited risk for pregnant women and suggested birth control as a strategy. Another pharmacist pointed to ZIKV “treatment.” No interviewee mentioned measures related to preparedness of pharmaceutical services.
PHC pharmacists do not place themselves at the frontline of risk reduction for the ZIKV epidemic. In the face of potential hazards and consequences of this disease, action by pharmacists is deemed critical. This study highlights pharmacist's misconceptions and lack of focused knowledge, pointing to the need for training and capacity-building in order to increase quality of care and positive management of future epidemics.
In Brazil, poverty-stricken population groups were the most affected by Zika virus (ZIKV). Women and children are fragile links that need focused attention, especially in relation to health care.
To investigate vulnerable, at-risk women in relation to their awareness of the ZIKV infection knowledge about the disease.
With evidence-based risk communication literature and consequences of ZIKV infection, a data collection instrument with open-ended questions was developed. Women from a small municipality in west-central Brazil, most from a rural setting, were interviewed at primary health care centers in April 2018. Interviews were recorded and transcribed. A preliminary analysis ensued.
Forty women were interviewed. The average age was 42.3 (21-74 yrs) and 39 women had at least one child. The average number of people living in the same home was 3.8 (1-18) and 24 homes (60%) had one to four children. Fourteen women (54%) were beneficiaries of income supplementation programs. Two interviewees mentioned they had never heard of Zika and eight (20%) had no actual knowledge to convey. Other groups had some knowledge about ZIKV. Fifteen (37.5%) associated ZIKV with mosquito bites and another 15 with pregnancy or birth defects. Ten women (25%) mentioned dengue or chikungunya, but only 7 (17.5%) were aware of symptoms. Only eleven women (27.5%) declared public health workers as information sources.
Positive aspects of awareness and knowledge were the tentative relationship some women made between pregnancy risk and exposure to mosquitoes, and with dengue or chikungunya. However, given ample media coverage and the severity of the epidemic, it is noteworthy to point out that all aspects were mentioned by fewer than half of the women. Health workers were not represented as relevant sources of information. Future in-depth content analysis of interviews may reveal important issues for risk communication strategies for this population.
The Zika virus (ZIKV) infection outbreak in Brazil surged in late 2014, peaking in 2015. The most affected region was the northeast, but Rio de Janeiro was especially affected in poor, vulnerable, low-income communities with inadequate sanitation and water. Most cases of the ZIKV-related neurologic syndrome, microcephaly, were detected among newborns coming from this environment.
To identify risk perception and consequences of ZIKV infection for pregnant women in a vulnerable community in Rio de Janeiro.
Forty women who frequented a primary health care center (PHC) in a ZIKV-prone area of Rio de Janeiro were interviewed based on an open-ended questionnaire on ZIKV infection and risk. No censorship regarding age or other demographic characteristics was applied. Interviews were transcribed and analyzed according to analytical categories stemming from the literature and prior work. Preliminary analysis focused on risks for pregnant women and other groups.
Absolute number of responses reflect density of issues within all responses. Age range was 15-60 years. Several women identified microcephaly as a consequence of ZIKV infection for newborns, but many respondents did not cite any health problem associated with ZIKA in pregnancy. Although some cited pregnant women and children as most vulnerable, people living in or near insalubrious environments, such as the elderly, and those with low immunity were more cited. Information was mostly obtained from health professionals and television. Many confused origin and symptoms of ZIKV infection with other arbovirus infections.
This vulnerable group of women, who continuously attend a PHC in the area, have had community experience with the disease and its consequences, showed surprisingly little knowledge as to the risks of ZIKV infection for pregnant women. Results may indicate that the health system has still not achieved adequate risk communication for at-risk women for ZIKV infection in Rio de Janeiro.
The research reported in this Research Communication evaluates the effect of milk acidification on the physicochemical and sensory properties of Licor de Oro (or Gold Liqueur; LO), a traditional alcoholic beverage produced in Chiloé island, Chile, which is made by mixing milk acidified with lemon juice and alcohol at a ratio of 1.0:1.0, along with sugar and other spices. The mixture is stored for a couple of weeks and then filtered to obtain a product with a yellowish-transparent appearance, sweetness and acidic taste, milky and alcoholic notes. The lack of information regarding LO processing, mainly in the amount of acid added to the mixture, leads to products of highly variable quality. Thus, the objective of this study was to evaluate the effect of milk acidification on the physicochemical and sensory properties of LO. Raw milk was acidified using citric acid to six different pH values: 6.7 (control), 6.0, 5.3, 4.6, 3.9 and 3.2. These milk treatments were then used to make LO. A decrease of milk pH led to LO with higher levels of sensorial and titratable acidity. LO obtained at pH 6.7 and 6.0 had higher levels of total protein than other treatments, leading to excessive turbidity. In contrast, treatments made at pH ≤5.3 had a typical transparent appearance of LO. These results suggest that a minimum level of milk acidification is required to obtain LO with desired appearance and composition.
Our purpose was to determine the effectiveness and harms of vaccination in patients with any sexual history to prevent the prevalence of papillomavirus infection. A search strategy was conducted in the MEDLINE, CENTRAL, EMBASE and LILACS databases. Searches were also conducted in other databases and unpublished literature. The risk of bias was evaluated with the Cochrane Collaboration's tool. Analysis of fixed effects was conducted. The primary outcome was the infection by any and each human papillomavirus (HPV) genotype, serious adverse effects and short-term adverse effects. The measure of the effect was the risk difference (RD) with a 95% confidence interval (CI). The planned interventions were bivalent vaccine/tetravalent/nonavalent vs. placebo/no intervention/other vaccines. We included 29 studies described in 35 publications. Bivalent HPV vaccine offers protection against HPV16 (RD −0.05, 95% CI −0.098 to −0.0032), HPV18 (RD −0.03, 95% CI −0.062 to −0.0004) and HPV16/18 genotypes (RD of −0.1, 95% CI −0.16 to −0.04). On the other side, tetravalent HPV vaccine offered protection against HPV6 (RD of −0.0500, 95% CI −0.0963 to −0.0230), HPV11 (RD −0.0198, 95% CI −0.0310 to −0.0085). Also, against HPV16 (RD of −0.0608, 95% CI −0.1126 to −0.0091) and HPV18 (RD of −0.0200, 95% CI −0.0408 to −0.0123). There was a reduction in the prevalence of HPV16, 18 and 16/18 genotypes when applying the bivalent vaccine, with no increase in adverse effects. Regarding the tetravalent vaccine, we found a reduction in the prevalence of HPV6, 11, 16 and 18 genotypes, with no increase in adverse effects.
Our objective was to determine the frequency of zika (ZIKV), chikungunya (CHIKV) and dengue (DENV) virus coinfection and describe the mortality cases that occurred during the epidemiologic surveillance of the ZIKV epidemic in Colombia. We analysed all cases of suspected ZIKV infection that were reported to the National Institute of Health (October 2015–December 2016). DENV, CHIKV and ZIKV RNA were detected in serum or tissue samples using polymerase chain reaction assay. Medical records of the fatal cases were reviewed. We identified that 23 871 samples were processed. The frequency of viral agents was 439 (1.84%) for DENV, 257 (1.07%) for CHIKV and 10118 (42.38%) for ZIKV. Thirty-four (0.14%) cases of coinfection were identified. The CHIKV–ZIKV coinfection was present in 28 cases (82.3%), DENV–CHIKV in three (8.8%) and DENV–ZIKV in three (8.8%). Seven (20.6%) coinfection cases were fatal (two DENV–CHIKV cases and five CHIKV–ZIKV cases). Two cases were foetal deaths and the others were related to neurological syndrome and sepsis. In conclusion, the frequency of arbovirus coinfection during epidemic of ZIKV was low, and CHIKV–ZIKV coinfection was the most common. Mortality was high among coinfection patients. The role of each virus in the mortality cases of coinfection warrants further studies.
The current study aims to evaluate the effects of increasing levels of xylanase enzyme (XYL) on sugarcane silage fermentation, fermentative losses, chemical composition, dry matter (DM), neutral detergent fibre (NDF) degradation and aerobic stability. A completely randomized design trial was performed with five treatments and 50 experimental silos. Treatments were: 0, 100, 200, 300 and 400 mg of XYL per kg of DM. XYL contained 10 000 U/g. There was a quadratic effect of XYL on silage pH and acetic acid concentration: lower pH and higher acetic acid concentrations were found at intermediary levels of the enzyme. XYL decreased lactic acid concentration linearly. Furthermore, the enzyme had a quadratic effect on effluent and total losses, with higher losses at intermediary XYL levels. There was a quadratic effect of XYL on organic matter (OM), non-fibre carbohydrates (NFC) and crude protein (CP) content. In addition, a quadratic effect of XYL was observed on NDF content and degradation. Intermediary levels of XYL showed higher concentration of OM and NFC. The addition of XYL had no effect on silage temperature and pH after aerobic exposure. Thus, intermediate levels of XYL increased acetic acid and decreased silage pH. Besides positive effects on silage composition, intermediary XYL levels decreased NDF degradation.
Many molluscs may be infected with angiostrongylid larvae. Following the histopathological diagnosis of abdominal angiostrongyliasis in a grape farmer from southern Brazil, molluscs in the area were investigated. During a nocturnal search, 245 specimens of slugs were collected and identified as the invasive Chinese slug Meghimatium pictum. Angiostrongylus costaricensis worms were recovered from mice that were experimentally infected with larvae obtained from 11 (4.5%) of the molluscs. This study presents the first report of M. pictum being identified as an intermediate host for A. costaricensis. Most of the slugs were collected from grape plants, which suggests that transmission may be associated with grape consumption.
Tourists approaching wild animals can potentially cause disturbance as a result of the perceived predation risk. Risk effects arise when prey alter their behaviour in response to predators. This response may carry costs through its impact on fitness-related activities such as foraging. We recorded behavioural responses of whale sharks Rhincodon typus to experimental vessel and swimmer approaches. We simulated the disturbance caused by ecotourism in the foraging site of this planktivorous fish in Bahia de Los Angeles, Gulf of Baja California, Mexico. Stress-related behaviours (vigilance, change of direction, diving and acceleration) were more common directly after both types of disturbance than before, in particular after approach by a swimmer. Individuals were more likely to be vigilant when they were new to the bay, but we did not find evidence of within-season behavioural habituation. Sharks were 24% more likely to forage before human stimuli than after. Our study highlights negative effects of vessel and swimmer approaches on whale shark behaviour, with a short-term increase in stress-related behaviours potentially carrying energetic costs, combined with a decrease in food intake following the disturbance. Our results indicate concerns about the impact of ecotourism on large fish species. An important next step would be to determine whether these short-term behavioural responses to the perception of predation risk negatively affect fitness. Among other guidelines, we recommend preventing swimmers from approaching if whale sharks stop feeding when a vessel approaches.
The hypothesis of the study was that inhibition of PPARβ/δ increases glucose uptake and lactose synthesis in bovine mammary epithelial cells by reducing the expression of the glucose transporter mRNA destabiliser calreticulin. Three experiments were conducted to test the hypothesis using immortalised bovine mammary alveolar (MACT) and primary bovine mammary (PBMC) cells. In Experiment 1, the most effective dose to inhibit PPARβ/δ activity among two synthetic antagonists (GSK-3787 and PT-s58) was assessed using a gene reporter assay. In Experiment 2, the effect on glucose uptake and lactose synthesis was evaluated by measuring glucose and lactose in the media and expression of related key genes upon modulation of PPARβ/δ using GSK-3787, the synthetic PPARβ/δ agonist GW-501516, or a combination of the two in cells cultivated in plastic. In Experiment 3, the same treatments were applied to cells cultivated in Matrigel and glucose and lactose in media were measured. In Experiment 1 it was determined that a significant inhibition of PPARβ/δ in the presence or absence of fetal bovine serum was achieved with ≥ 1000 nm GSK-3787 but no significant inhibition was observed with PT-s58. In Experiment 2, inhibition of PPARβ/δ had no effect on glucose uptake and lactose synthesis but they were both increased by GW-501516 in PBMC. The mRNA abundance of PPARβ/δ target gene pyruvate dehydrogenase kinase 4 was increased but transcription of calreticulin was decreased (only in MACT cells) by GW-501516. Treatment with GSK-3787 did not affect the transcription of measured genes. No effects on glucose uptake or lactose synthesis were detected by modulation of PPARβ/δ activity on cells cultivated in Matrigel. The above data do not provide support for the original hypothesis and suggest that PPARβ/δ does not play a major role in glucose uptake and lactose synthesis in bovine mammary epithelial cells.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.