Berberine-fluconazole microparticle-based combination therapy to treat candidiasis infections.

AIM: This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. METHODS AND RESULTS: Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time-kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 µg ml-1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time-kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. CONCLUSION: Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR-FLU microparticles in formulations have potential as antifungal therapy.

Economic costs related to coronavirus disease 2019 pandemic: A systematic literature review.

Due to the COVID-19 pandemic, the pressure on healthcare systems has been tremendous and it is having a huge economic impact. The objective of this paper is to carry out a systematic literature review of the publications that have analysed the costs derived from COVID-19 from the patient's perspective. Not only is this study aimed at measuring the impact of COVID-19 in economic terms, but also in qualitative terms, analysing, for instance, the types of costs (direct and indirect) and their variations depending on the geographical area under study. Searches were conducted in PubMed, Cochrane Library, Web of Science and Scopus. The time frame for the analysis was from the start of the pandemic until 9th December 2021. A total of 322 papers were found. The number of articles assessed for eligibility was 32, and after applying the exclusion criteria, 13 papers were included in the qualitative synthesis. Most of the studies analysed only direct costs (69.23%) and were focused on Asia (61.54%), where the larger indirect costs, as well as the greater total costs, were found. However, the higher costs per patient and year were shown for the United States. This investigation showed the importance of COVID-19 in national, regional and local budgets. More studies are to be developed in Europe due to both the existing differences in the health care systems and financing by country and the difference in the incidence of COVID-19 by country and wave.

The associations between suicides, economic conditions and social isolation: Insights from Spain.

Suicide is among the main challenges that need to be addressed in developed countries. In this paper, we analyse suicides across the 17 Spanish regions over the period 2014-2019. More precisely, our objective is to re-study the determinants of suicides focusing on the latest economic expansion period. We use count panel data models and sex stratification. A range of aggregate socioeconomic regional-level factors have been identified. Our empirical results show that: (1) a socioeconomic urban-rural suicide gaps exist; (2) there are significant gender differences, for the women a Mediterranean suicide pattern appears whereas unemployment levels have a significant importance for men, (3) social isolation factors, when significant, they show an (a priori) surprisingly positive result. We provide new highlights for suicide prevention in Spain. Precisely, it is highlighted that jointly policies by gender and attending to vulnerable groups are both necessary.

Coronavirus fear of contagion and compliance with social distancing measures: evidence for a sample of a Spanish university community.

Background: Social distancing measures have been one of the core pillars of the strategy against COVID-19 in all the countries. This study aims at understanding what motivates behaviours and compliance with social distancing measures among students and workers from a Spanish public university. Methods: We carry out two logistics models considering two different dependent variables: not maintaining social relation with non-cohabiting people and not to leave home except for emergencies (n = 507, sample is formed by students and workers from the University of Cantabria in the North of Spain). Results: Being very concerned about getting ill suggests higher risk of not maintaining social relation with non-cohabiting people. Getting older increase the probability of not leaving home except for emergencies as happens with those who are very concerned about getting ill. Young people often living with vulnerable older relatives may affect students' behaviour. Conclusions: Our findings suggest that compliance with social distancing measures depends on several factors related to age, the number or kind of cohabiting people and level of concern about getting ill. Policies should address all these factors through a multidisciplinary perspective.

[Impact of digital pathology implementation in Reunion Island]. / Intérêt de la pathologie numérique à La Réunion.

In recent decades, the major scientific advances in oncology have complexified anatomic pathology practice. Collaboration with local and national pathologists is essential for ensuring a high-quality diagnosis. Anatomic pathology is undergoing a digital revolution that implements whole slide imaging in routine pathologic diagnosis. Digital pathology improves diagnostic efficiency, allows remote peer review and consultations (telepathology), and enables the use of artificial intelligence. The implementation of digital pathology is of particular interest in isolated territories, facilitating access to expertise and therefore to specialized diagnosis. This review discusses the impact of digital pathology implementation in French overseas territories, particularly in Reunion Island.

A systematic review on suicide because of social isolation/and loneliness: does COVID-19 make a difference?

BACKGROUND: Suicide is a significant cause of death worldwide. Various purposes can explain why people choose to attempt or commit suicide such as mental-health disorders, income-related-factors, quality of life or issues related to social context. This study aims to identify an updated association between 'isolation' and suicides. METHODS: In this regard, we had made a systematic review of the most recent papers, published from January 2016 to March 2022, thought the most acknowledged databases. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. To the best of our knowledge, this issue is very important due to the indirect relationship between COVID-19 and suicides. RESULTS: Our analysis demonstrates that suicide and -social isolation and loneliness- have a positive and direct relationship although these findings varied slightly by areas. Moreover, most of the attention is focused on the youth during the most recent period and this is a real problem because economies cannot afford losing (young) population. CONCLUSIONS: In order to prevent suicides, public policies should prevent suicidal thoughts that it could induce to terminate the lives of individuals in their most productive years and harmful outcomes to their families and friends.

Change in eating habits during the Spanish COVID-19 pandemic lockdown: evidence for a sample of university community.

Background: The stress and anxiety caused by COVID-19 lockdown may have changed the eating habits of the population. Our aim is to assess the eating changes that have taken place due to the pandemic. Methods: Data were collected through an electronic survey created by the Health Economics Research Group of the University of Cantabria and IDIVAL and conducted between 14/01/2021 and 19/02/2021. A total of 1,417 responses were recorded, but only 507 complete observations were considered. We carried out a cross-sectional analysis through ordered probit regressions. Results: The improvement in post-confinement eating habits is associated with higher income level, better self-assessed health status and more physical activity. The worsening of eating habits is associated with having a certain level of nomophobia or the fear of contagion. Conclusions: Our analysis can be used for designing and implementing new strategies to overcome the negative spill overs of the COVID-19 pandemic and improve the dietary patterns.

Serum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility.

OBJECTIVE: Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomarkers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored. METHODS: Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale-Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis. RESULTS: A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome. CONCLUSIONS: UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome.

Acute macular neuroretinopathy in a patient with birdshot chorioretinopathy after intravitreal triamcinolone suspension injection.

PURPOSE: To report a case of acute macular neuroretinopathy (AMN) after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema secondary to birdshot chorioretinopathy. METHOD: A case report. PATIENT: A 62-year-old female. RESULTS: The patient presented with acutely decreased vision and a ring scotoma around her central vision three days after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema in her right eye (OD) secondary to birdshot chorioretinopathy. She had undergone pars plana vitrectomy, cataract extraction, and secondary intraocular lens implantation OD three months prior to the recent injection. Best-corrected visual acuity (BCVA) was 20/1000 OD and 20/50 OS. Intraocular pressure was 21 mmHg OD and 12 mmHg OS. Fluorescein angiography demonstrated a hypofluorescent area in the perifoveal zone OD. Optical coherence tomography OD depicted hyperreflective areas in the outer nuclear layer, outer plexiform layer, and retinal pigment epithelium. We diagnosed her with AMN OD and started her on brimonidine three times a day OD. She came back a week later with resolved scotoma and her vision improved to 20/60 OD. Five weeks later, BCVA was 20/40 and Intraocular pressures (IOP) was 12 mmHg OD. CONCLUSIONS AND IMPORTANCE: Intravitreal triamcinolone injection may be a cause of AMN with cystoid macular edema (CME) and borderline-high intraocular pressure. Brimonidine may be an effective treatment for these patients in the early course of the disease.

Potential of Tetradenia riparia leaf essential oil and its fractions in controlling Aedes aegypti and Rhipicephalus microplus larvae

Tetradenia riparia (Hochst.) Codd (Lamiaceae) is a shrub, commonly known as ginger bush or false myrrh, and several studies have shown that T. riparia exhibits a variety of biological properties. This study aimed to determine the chemical composition of T. riparia essential oil and its fractions, investigate their anticholinesterase activity, and assess their larvicidal activity against the cattle tick Rhipicephalus microplus and the mosquito Aedes aegypti. Eleven essential oil fractions were obtained by fractionation and analyzed by gas chromatography/mass spectrometry. Larvicidal activity against R. microplus and third-instar A. aegypti was assessed using a larval packet test and a larval immersion test, respectively. Anticholinesterase activity was determined by a bioautographic method. Forty-nine compounds were identified in the essential oil, of which the major classes were oxygenated sesquiterpenes (45.95%) and sesquiterpene hydrocarbons (35.20%) and the major components were isospathulenol (17.40%), ß-caryophyllene (15.61%), 14-hydroxy-9-epi-caryophyllene (10.07%), 14-hydroxy-α-muurolene (8.32%), and 9ß,13ß-epoxy-7-abietene (5.53%). Bioassays showed that T. riparia essential oil (LC50 = 1.56 µg/mL) and FR3 (LC50 = 0.30 µg/mL) were the most active against R. microplus and A. aegypti larvae, respectively. The essential oil and FR1, FR2, and FR3 exhibited acetylcholinesterase inhibitory activity. These results indicate that T. riparia essential oil and its fractions hold promise in the development of novel, environmentally safe agents for the control of R. microplus and A. aegypti larvae.

Y-chromosome target enrichment reveals rapid expansion of haplogroup R1b-DF27 in Iberia during the Bronze Age transition.

The Y chromosome can yield a unique perspective into the study of human demographic history. However, due to the repetitive nature of part of its sequence, only a small set of regions are suitable for variant calling and discovery from short-read sequencing data. These regions combined represent 8.9 Mbp or 0.14% of a diploid human genome. Consequently, investing in whole-genome sequencing to resolve Y-chromosome questions is poorly efficient. Here we use, as an alternative, target enrichment technology to greatly increase sequencing effectiveness, validating and applying the technique to 181 males, for 162 of whom we obtained a positive result. Additionally, 75 samples sequenced for the whole genome were also included, for a total sample size of 237. These samples were chosen for their Y chromosome haplogroup: R1b-DF27. In the context of European populations, and particularly in Iberia, this haplogroup stands out for its high frequency and its demographic history. Current evidence indicates that the diffusion of this haplogroup is related to the population movements that mark the cultural Bronze Age transition, making it remarkably interesting for population geneticists. The results of this study show the effects of the rapid radiation of the haplogroup in Spain, as even with the higher discriminating power of whole sequences, most haplotypes still fall within the R1b-DF27* paragroup rather than in the main derived branches. However, we were able to refine the ISOGG 2019-2020 phylogeny, and its two main subbranches, namely L176.2 and Z272, which present geographical differentiation between the Atlantic and Mediterranean coasts of Iberia.

Sequence diversity of the uniparentally transmitted portions of the genome in the resident population of Catalonia.

Genomic reference databases of residing populations are available in different countries and regions. Since they represent the whole genetic diversity of a geographical region, they have wide applications, from biomedical studies to forensic identifications. Uniparentally transmitted portions of the genome specifically are highly suitable for kinship analyses, mixed DNA cases and geographical ancestry inferences. We have sampled 808 individuals currently residing in Catalonia within the GCAT cohort, from which we have generated 808 high-quality whole mitochondrial DNA (mtDNA) genomes and 399 sequences of the male-specific part of the Y chromosome (MSY). We observe higher genetic diversity than in classical population genetics datasets. We test the robustness of whole sequences for unequivocal identifications, and we found that they have higher resolution than mitochondrial control region and Y chromosome short tandem repeats (Y-STRs), and that most of the variants they present are at low frequencies, increasing the discrimination capacity between individuals. These results confirm the forensic applicability of whole uniparental sequences and provide one of the largest high-quality reference datasets ever published.

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Intracranial Pressure Monitoring in Patients With Severe Traumatic Brain Injury: Extension of the Recommendations and the Effect on Outcome by Propensity Score Matching.

BACKGROUND: Intracranial pressure (ICP) monitoring is recommended for patients with traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) <9 on admission and revealing space-occupying lesions or swelling on computed tomography. However, previous studies that have evaluated its effect on outcome have shown conflicting results. OBJECTIVE: To study the effect of ICP monitoring on outcome after adjustment of patient's characteristics imbalance and determine the potential benefit on patients with higher GCS that deteriorates early or in the absence of computed tomography results suggesting high ICP. METHODS: We searched for adult patients with TBI admitted between 1996 and 2020 with a GCS <9 on admission or deterioration from higher scores within 24 hours after TBI. Patients were divided into groups if they fulfilled strict (Brain Trauma Foundation guidelines) or extended criteria (patients who worsened after admission or without space-occupying lesions) for ICP monitoring. Propensity score analyses based on nearest neighbor matching was performed. RESULTS: After matching, we analyzed data from 454 patients and 184 patients who fulfilled strict criteria or extended criteria for ICP monitoring, respectively. A decreased on in-hospital mortality was detected in monitored patients following strict and extended criteria . Those patients with a higher baseline risk of poor outcome showed higher odds of favorable outcome if they were monitored. CONCLUSION: ICP monitoring in patients with severe TBI within 24 hours after injury following strict and extended criteria was associated with a decreased in-hospital mortality. The identification of patients with a higher risk of an unfavorable outcome might be useful to better select cases that would benefit more from ICP monitoring.

Larvicidal activity of Brunfelsia uniflora extracts on Aedes aegypti larvae.

The aim of this study was to evaluate the chemical composition and the larvicidal activity of Brunfelsia uniflora leaf and flower extracts against Aedes aegypti larvae. Twenty-four compounds were found in the leaf extract, and the major compounds were phytol (23.1%), 9,12,15-octadecatrienoic acid, ethyl ester (21.3%), and hexadecanoic acid, ethyl ester (12.8%). In the flower extract, twenty-four compounds were also identified and the major compounds were α-amyrin (35.7%), ß-amyrin (16.4%), and (EE)-geranyl linalool (9.6%) by gas chromatography coupled to mass spectrometry. The larvicidal activity was evaluated by larval immersion test. The lethal concentrations (LC) obtained from leaf extract were LC50 = 4.89 and LC99.9 = 11.14 mg/mL and from flower extract were LC50 = 3.82 and LC99.9 = 11.03 mg/mL, and the positive control presented LC50 = 0.40 and LC99.9 = 1.14 mg/mL. Thus, B. uniflora extracts are promising alternatives to control A. aegypti larvae.

Chemical composition of Tradescantia pallida (Rose) D.R. Hunt var. purpurea Boom (Commelinaceae) essential oil.

Tradescantia pallida is a herbaceous plant with promising compounds in its composition that can be applied in several areas such as agronomic, pharmaceutical and chemical. However, further studies on this plant are needed in order to characterise it phytochemically, pharmacologically and toxicologically. In this sense, the present study aimed to verify the unprecedented identification of its essential oil (EO) components. The EO extraction of T. pallida aerial parts was performed by hydrodistillation in a Clevenger apparatus (5 h), and the chemical analysis by gas chromatography coupled to mass spectrometry. The oxygenated sesquiterpene was the dominant class in EO composition and spathulenol (19.56%) was the principal identified compound, followed by caryophyllene oxide (18.84%), ß-caryophyllene (13.65%) and α-copaene (6.08%). The chemical identification of sesquiterpene compounds (oxygenated and hydrocarbons) in EO contributes to the understanding of the biological activities evidenced by T. pallida reported by literature.