A study of differential microRNA expression profile in migraine: the microMIG exploratory study.

BACKGROUND: Several studies have described potential microRNA (miRNA) biomarkers associated with migraine, but studies are scarcely reproducible primarily due to the heterogeneous variability of participants. Increasing evidence shows that disease-related intrinsic factors together with lifestyle (environmental factors), influence epigenetic mechanisms and in turn, diseases. Hence, the main objective of this exploratory study was to find differentially expressed miRNAs (DE miRNA) in peripheral blood mononuclear cells (PBMC) of patients with migraine compared to healthy controls in a well-controlled homogeneous cohort of non-menopausal women. METHODS: Patients diagnosed with migraine according to the International Classification of Headache Disorders (ICHD-3) and healthy controls without familial history of headache disorders were recruited. All participants completed a very thorough questionnaire and structured-interview in order to control for environmental factors. RNA was extracted from PBMC and a microarray system (GeneChip miRNA 4.1 Array chip, Affymetrix) was used to determine the miRNA profiles between study groups. Principal components analysis and hierarchical clustering analysis were performed to study samples distribution and random forest (RF) algorithms were computed for the classification task. To evaluate the stability of the results and the prediction error rate, a bootstrap (.632 + rule) was run through all the procedure. Finally, a functional enrichment analysis of selected targets was computed through protein-protein interaction networks. RESULTS: After RF classification, three DE miRNA distinguished study groups in a very homogeneous female cohort, controlled by factors such as demographics (age and BMI), life-habits (physical activity, caffeine and alcohol consumptions), comorbidities and clinical features associated to the disease: miR-342-3p, miR-532-3p and miR-758-5p. Sixty-eight target genes were predicted which were linked mainly to enriched ion channels and signaling pathways, neurotransmitter and hormone homeostasis, infectious diseases and circadian entrainment. CONCLUSIONS: A 3-miRNA (miR-342-3p, miR-532-3p and miR-758-5p) novel signature has been found differentially expressed between controls and patients with migraine. Enrichment analysis showed that these pathways are closely associated with known migraine pathophysiology, which could lead to the first reliable epigenetic biomarker set. Further studies should be performed to validate these findings in a larger and more heterogeneous sample.

[Cervicocranial arterial dissection. Experience in 57 patients]. / Caracterización clínica e imagenológica de una serie de pacientes con disección de arterias cervicales e intracraneales.

BACKGROUND: Cervicocranial arterial dissection (CIAD) is an important cause of stroke. AIM: To describe the clinical and imaging characteristics of patients with CIAD. MATERIAL AND METHODS: An anonymous registry was made including all patients admitted to a private hospital with a diagnosis of CIAD. Patients were subdivided as having an anterior or posterior circulation dissection (ACD or PCD, respectively). RESULTS: Fifty-seven patients aged 40 ± 8 years (60% women) were included in the study, 39 with PCD and 18 with ACD. Cervical pain was the most common symptom. CIAD was diagnosed with no clinical or imaging signs of stroke in 49% of patients. Fifty one percent of patients had focal neurological deficits and 72% had a NIH stroke score below five. No significant differences between patients with ACD or PCD were found. Fifty patients received antiplatelet therapy (simple or dual), seven patients were anticoagulated and 13 were subjected to stenting due to progression of stenosis with hemodynamic involvement or bilateral dissection with scarce collaterals. The lesion was located in V3 segment in 27 patients and cervical segment of the internal carotid in 16 cases. A favorable Modified Rankin Scale (0-2) was achieved in 85.9%, with a trend towards achieving better functional prognosis in PCD. CONCLUSIONS: Due to the greater availability of non-invasive imaging methods, 50% of these patients with CIAD did not have a stroke. Thus, an earlier and more timely management is feasible.

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers.

BACKGROUND: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. METHODS: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. RESULTS: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. CONCLUSIONS: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.

Evaluation of the concomitant use of oral preventive treatments and onabotulinumtoxinA in chronic migraine: the PREVENBOX study.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA is an effective preventive treatment for chronic migraine (CM). In CM, in addition to a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumtoxinA in patients with CM. METHODS: This was a retrospective, multicentric, cross-sectional study. Patients with CM (International Classification of Headache Disorders-3beta) that had been treated with onabotulinumtoxinA were enrolled consecutively. We collected parameters related to each patient's pre-treatment situation, as well as their current situation, focusing on frequency and intensity of migraine, number of oral prophylactics and the respective cycle of onabotulinumtoxinA. Univariate and logistic regression analyses were performed. RESULTS: We included 542 patients, 90.0% of whom were taking oral preventive treatments. During treatment with onabotulinumtoxinA, 47.8% withdrew at least one prophylactic and 41.6% stopped using oral prophylactics altogether. Factors associated with a reduction or cessation of oral prophylactics were >50% improvement in frequency and intensity, remission to episodic migraine, use of topiramate as an initial treatment, increased number of infiltrations and shorter chronification period (P < 0.05). The multivariate analysis showed that a chronification period <20 months, more than five cycles of onabotulinumtoxinA, >50% improvement in pain intensity and topiramate as an initial treatment were predictors of a reduction in oral prophylactics (area under the curve, 70.3%; P < 0.001). CONCLUSIONS: Our study demonstrated the efficacy and safety of onabotulinumtoxinA. This treatment reduced the use of oral prophylactics. Withdrawal of oral prophylactics was most likely to occur after five cycles of treatment.

Early efficacy and late gain in chronic and high-frequency episodic migraine with onabotulinumtoxinA.

BACKGROUND AND PURPOSE: The aim was to analyse the clinical characteristics of a long-term follow-up of patients with chronic and high-frequency episodic migraine in treatment with onabotulinumtoxinA. METHODS: Patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) according to the International Classification of Headache Disorders 3 beta were included. A comparative analysis was carried out at each study time point identifying outcome measures according to initial diagnosis and treatment duration. RESULTS: In all, 578 patients were recruited and after 24 months outcome data were collected from 100 patients: 84.0% CM and 16.0% HFEM. After 24 months, headache frequency was significantly reduced by 10.5 days from baseline, 64.0% reported a ≥50% reduction in pain intensity and 70.0% of patients had ≥50% reduction in analgesic use. Comparing baseline diagnoses, at month 6 CM patients presented higher mean reduction in frequency (CM 44.3% ± 32.6% vs. HFEM 34.6% ± 24.8%) and analgesic use (CM 53.6% ± 35.4% vs. HFEM 39.3% ± 33.2%). At month 12, the mean reduction in frequency was similar in CM and HFEM patients (CM 44.7% ± 33.4% vs. HFEM 41.2% ± 28.2%). Improvement in pain intensity, analgesic use and Migraine Disability Assessment were proportional in both diagnoses. CONCLUSIONS: OnabotulinumtoxinA efficacy is significant at 6 months in frequency and analgesic intake and remains stable during follow-up, whilst the intensity of pain decreases in a stepwise manner at each time point of the analysis. The improvement in CM and HFEM patients is proportional and significant after 1 year of treatment.

Oral health in Alzheimer's disease: a multicenter case-control study.

OBJECTIVES: The aim of this case-control study was to carry out an oral health assessment on a group of Alzheimer's patients and to establish a hypothesis regarding the implication of the characteristics of the disease and the treatment of oral health. MATERIALS AND METHODS: A total of 70 Alzheimer's patients, residents at the Alzheimer Center Reina Sofia Foundation (Madrid, Spain) and at the Alzheimer State Reference Center (Salamanca, Spain), and 36 controls (companions/acquaintances), were studied by oral examination and saliva sampling. The oral health indices DMFT/DMFS, CPI, the prosthetic condition, oral hygiene, saliva volume, and pH, as well as the specific microbiological parameters governing the risk of developing caries were assessed. RESULTS: Alzheimer's patients exhibited, as compared to the control group, (1) fewer teeth (10.9 ± 10.5 vs 23.7 ± 6.5), (2) fewer obturations (2.2 ± 3.4 vs 6.6 ± 5.6), (3) fewer periodontally healthy sextants (0.1 ± 0.4 vs 1.4 ± 2.2), (4) worse oral hygiene (43.1 vs 72.2% brushed), (5) greater use of removable prostheses (47.8 vs 8.4%), (6) higher incidence of candida infection (11.8 vs 0.0%) and cheilitis (15.9 vs 0.0%), (7) lower salivary flow (0.6 ± 0.6 vs 1.1 ± 0.6), and (8) lower buffering capacity (46 vs 80%). CONCLUSIONS: After taking into account the influence of age, Alzheimer's patients had worse oral health (caries and periodontal disease), more mucosal lesions (cheilitis and candidiasis), and worse saliva quantity and quality. CLINICAL RELEVANCE: Clinicians should be aware of the implications of Alzheimer's disease in oral health, in order to stablish the effective preventive measures and the optimal treatment plan.

[Myasthenia gravis and its association with lymphoproliferative disorders: a case series]. / Miastenia gravis y su asociación con trastornos linfoproliferativos: casos clínicos.

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. It is characterized by variable weakness and excessive fatigability of skeletal muscles. In the last few years, numerous reports have been published showing the association between autoimmune diseases, such as systemic erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The association between MG and lymphoid neoplasia seems to be less frequent. To analyze this association we reviewed the MG patients in the Department of Neurology, Hospital Salvador of Santiago, Chile. During a three-year period we identified four patients who developed different lymphoproliferative disorders: two with B-cell lymphoma, one with chronic lymphocytic leukaemia and one plasmacytoma with an associated amyloidosis. The MG was generalized but mild, all cases classified as type IIa according to the definition proposed by the MG Foundation of America. The neoplasia appeared two to 36 years after the onset of MG. These cases provide additional evidence of the association between MG and lymphoproliferative disorders.

[Toxic encephalopathy caused by liquefied gas exposure: Report of one case]. / Encefalopatía tóxica por isopropanol: Sobre-exposición accidental a gas propano.

Liquefied hydrocarbon gas, such as propane is considered safe. However there are reports that voluntary exposure to liquefied gas at least could originate hallucinatory states. We report a 20 years old woman who was found in a coma with extensor muscle hypertonia, brisk tendon reflexes and extensor plantar (Babinski) responses after being exposed to propane gas. The brain magnetic resonance imaging (MRI) showed lesions in both hippocampi and white matter in the oval center. The patient had a normal oxygen saturation of 98%, a carboxyhemoglobin of 1.6% and a metabolic acidosis with a pH of 7.01 with an anion gap of 16 mEq/l. This pattern suggested that it was a consequence of the intermediary metabolism of isopropanol. The recovery of the patient was slow and four months later she still had lesions on MRI and limitations in her cognitive sphere, memory and executive functions. Thus, liquefied gas exposure can cause a toxic encephalopathy with a persistent damage of the central nervous system.

Impact of functional mandibular advancement appliances on the temporomandibular joint - a systematic review.

BACKGROUND: Although many orthodontists have no doubts about the effectiveness of functional appliances for mandibular advancement, the impact on the temporomandibular joint (TMJ) is still in dispute. The objective of this systematic review is to examine the main effects on the TMJ of using functional appliances, both in healthy patients and in patients with a pre-existing disorder. MATERIAL AND METHODS: A systematic review of the literature was conducted in accordance with the PRISMA guidelines. Only systematic reviews, meta-analyses, randomized clinical trials (RCTs), case-control studies and cohort studies were included. A detailed language-independent electronic search was conducted in the Pubmed, Scopus, Cochrane Library and Embase databases. All studies published between 2000 and 2015 were included. RESULTS: A total of 401 articles were identified. Of these, 159 were duplicates and were excluded. On reading the title and abstract, 213 articles were excluded because they did not answer the research question, leaving a total of 29 articles. These articles were read and assessed. Following critical reading of the full text, eight articles were excluded: seven because they were considered of low quality and one because it published redundant data. As a result, 21 articles were included. CONCLUSIONS: After treatment with functional appliances, the condyle was found to be in a more advanced position, with remodelling of the condyle and adaptation of the morphology of the glenoid fossa. No significant adverse effects on the TMJ were observed in healthy patients and the appliances could improve joints that initially presented forward dislocation of the disk.

Estimating influenza vaccine effectiveness in Spain using sentinel surveillance data.

We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case­control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0­14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.

Estimation of the density of veins from susceptibility-weighted imaging by using Mamdani fuzzy-type rule-based system. Investigating the neurovascular coupling in migraine.

BACKGROUND AND PURPOSE: An impaired neurovascular coupling has been described as a possible player in neurodegeneration and cognitive decline. Migraine is a recurrent and incapacitating disorder that starts early in life and has shown neurovascular coupling abnormalities. Despite its high prevalence, the physiology and underlying mechanisms are poorly understood. In this context, new biomarkers from magnetic resonance imaging (MRI) are needed to bring new knowledge into the field. The aim of this study was to determine the vein density from Susceptibility-Weighted Imaging (SWI) MRI, in subjects with migraine and healthy controls; and to assess whether it relates to Resting-State functional MRI (RS-fMRI). MATERIALS AND METHODS: The cohort included 30 healthy controls and 70 subjects with migraine (26 episodic, 44 chronic) who underwent a brain 3.0 T MRI. Clinical characteristics were also collected. Maps of density of veins were generated based on a Mamdani Fuzzy-Type Rule-Based System from the SWI MRI. Mean values of vein density were obtained in grey (GM) and white matter (WM) Freesurfer lobar parcellations. The Amplitude of Low-Frequency Fluctuations (ALFF) image was calculated for the RS-fMRI, and the mean values over the parcellated GM lobes were estimated. Differences between groups were assessed through and analysis of variance (age, sex, education and anxiety as covariates; p < 0.05), followed by post-hoc comparisons. Associations were run between clinical and MRI-derived variables. RESULTS: When comparing the density of veins in GM, no differences between groups were found, neither associations with clinical variables. The density of veins was significantly higher in the WM of the occipital lobe for subjects with chronic migraine compared to controls (30%, p < 0.05). WM vein density in either frontal, temporal or cingulate regions was associated with clinical variables such as headache days, disability scores, and cognitive impairment (r between 0.25 and 0.41; p < 0.05). Mean values of ALFF did not differ significantly between controls and subjects with migraine. Strong significant associations between vein density and ALFF measures were obtained in most GM lobes for healthy subjects (r between 0.50 and 0.67; p < 0.05), instead, vein density in WM was significantly associated with ALFF for subjects with migraine (r between 0.32 and 0.58; p < 0.05). CONCLUSIONS: Results point towards an increase in vein density in subjects with migraine, when compared to healthy controls. In addition, the association between GM vein density and ALFF found in healthy subjects was lost in migraine. Taken together, these results support the idea of abnormalities in the neurovascular coupling in migraine. Quantitative SWI MRI indicators in migraine might be an interesting target that may contribute to its comprehension.

The MIGREX study: Prevalence and risk factors of sexual dysfunction among migraine patients.

BACKGROUND: Migraine attacks have a high impact on daily activities. There is limited research on the burden of migraine on sexual functioning. OBJECTIVE: To determine the prevalence of sexual dysfunction in patients with migraine and its relationship with migraine features and comorbidities. METHOD: This is a cross-sectional study. We included migraine patients between 18 and 60 years-old from 8 Headache Clinics in Spain. We recorded demographic data and migraine features. Patients fulfilled a survey including comorbidities, Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale and a questionnaire about migraine impact on sexual activity. A K-nearest neighbor supervised learning algorithm was used to identify differences between migraine patients with and without sexual dysfunction. RESULTS: We included 306 patients (85.6% women, mean age 42.3±11.1 years). A 41.8% of participants had sexual dysfunction. Sexual dysfunction was associated with being female (OR [95% CI]: 2.42 [1.17-5.00]; p<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.

Genomic Characterization of Mycoplasma arginini Isolated from a Housefly on a Dairy Farm and Comparison with Isolates from Bovine Milk and Lung Tissue.

Mycoplasma mastitis can be highly contagious, unresponsive to treatment, and cause severe economic problems in affected herds. Notable routes of Mycoplasma spp. transmissions are contaminated milking equipment and animal contact through respiratory secretions. Only a few studies report the environment as a possible source of infection. Our group studied the presence of pathogens in houseflies (Musca domestica) in a New York State dairy in the United States. Among others, a Mycoplasma spp. was found in the gut of a housefly captured in the sick pen and identified as M. arginini. Here, we characterized its genome and investigated its relatedness with eight isolates from milk, one isolate from lung tissue collected in the same dairy, and five other dairies in New York State. We applied whole-genome sequencing and phylogenetic analysis based on the sequences of the 16S rRNA gene and 76 conserved proteins. We also assessed an in silico virulence profile by considering a panel of 94 putative virulence genes. As a result of the genome analysis, the housefly M. arginini isolate was highly similar to the milk isolates; interestingly, the similarity was highest with M. arginini isolated from milk on the same dairy farm where the housefly was captured. The housefly and milk M. arginini isolates possessed 54 of the 94 pathogenicity genes considered. Our data support the hypothesis that houseflies are carriers of Mycoplasma spp. and can be considered within the possible roots of environmental transmission of infection in dairy cows. Nevertheless, M. arginini pathogenicity will need to be investigated with dedicated studies. IMPORTANCE It is critical to control the spread of bovine mastitis caused by Mycoplasma spp., as this disease can be highly contagious and have a severe economic impact on affected dairies. A better understanding of possible transmission routes is crucial for infection control and prevention. Based on our data, the composite milk isolates are genetically similar to the housefly isolate. This provides evidence that the same Mycoplasma species found in milk and associated with mastitis can also be isolated from houseflies captured in the dairy environment.

Early estimates of the effectiveness of the 2011/12 influenza vaccine in the population targeted for vaccination in Spain, 25 December 2011 to 19 February 2012.

We present early estimates of influenza vaccine effectiveness (VE) in the population targeted for vaccination, during 25 December 2011 to 19 February 2012. The adjusted VE was 55% (95% CI: 3 to 79) against any type of influenza virus and 54% (95% CI: 1 to 79) against influenza A(H3N2) virus. This suggests a moderate protective effect of the vaccine in the targeted population in a late influenza epidemic with limited match between vaccine and circulating strains.

The use of occlusal indices in high-impact literature.

UNLABELLED: Malocclusion is difficult to define because individuals and cultures vary widely in their perceptions of what constitutes an occlusal problem. A number of occlusal indices have been devised but, probably because of this perceptual problem, none has ever emerged as a standard. OBJECTIVE: The main objective was to review the use of the principal occlusal indices. BASIC RESEARCH DESIGN: The PUBMED database was searched for the main occlusal indices employed, journals with an impact in dentistry and specialist orthodontics journals. RESULTS: The occlusal indices most frequently employed were IOTN (163 studies), PAR (132 studies), DAI (68 studies) and ICON (32 studies). The journals publishing the greatest number of studies using these occlusal indices are those specialising in orthodontics. CONCLUSIONS: In the high-impact scientific literature, the indices in greatest use are IOTN, followed by PAR, DAI and ICON. DAI and IOTN are mainly used in epidemiological or prevalence studies, while PAR is generally used for longitudinal studies. IOTN is used more in Europe. DAI is used worldwide; though least in Europe.

Pathogens associated with houseflies from different areas within a New York State dairy.

Houseflies (Musca domestica) are nonbiting muscoids of importance because they can be mechanical vectors of many kinds of pathogens such as bacteria, protozoa, viruses, and helminth eggs. This study aimed to evaluate the bacterial communities associated with houseflies captured in 3 different areas on a dairy farm located in New York State. Variations in the bacterial community were also evaluated based on the flies' sex and external or internal location where the bacteria were isolated. A total of 101 flies were collected: 27 flies from the sick pen, 42 from calf hutches, and 32 from the milking parlor. A total of 485 organisms were isolated, 233 (48.0%) from 53 female flies and 252 (52.0%) from 48 male flies. Most (74%) bacteria were found in the internal parts of the flies, with only 26% isolated from the external surfaces. The number of isolates detected per fly ranged between 1 and 11. A total of 392 bacteria were identified at the species level. We isolated 26 species reported to be bovine contagious or environmental mastitis pathogens. Within the group of organisms considered contagious, we isolated Staphylococcus aureus and Mycoplasma arginini. This was the first time that a Mycoplasma species was isolated from houseflies. We identified 5 organisms considered foodborne pathogens that affect human health: Salmonella spp., Escherichia coli, Staph. aureus, Bacillus cereus, and Bacillus subtilis. Four of the organisms isolated in this study were also linked with milk spoilage, including Pseudomonas aeruginosa, Bacillus cereus, Bacillus licheniformis, and Paenibacillus lactis. This study confirmed that houseflies carry a high bacterial diversity, including organisms associated with animal infections, organisms that could be a concern for public health, or organisms that could negatively affect milk quality.

Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.

Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated doses at short intervals. The use of biocompatible polymers such as ethylcellulose has made it possible to develop microencapsulated formulations which facilitate liquid, sustained-release pharmaceutical formulas for oral administration. We developed a stable final formulation of morphine with an acceptable release profile by comparing the rheological properties and stability of formulations with different thickeners (xanthan gum, Carbopol, and carboxymethylcellulose with microcrystalline cellulose) at different concentrations from 0.25% to 1.0%. Release assays in a Franz-type cell were done to determine the most suitable release profile for the formulation.

Elaboration, characterization, and stability study of a sunscreen emulsion for use as a towelette application in pediatric photoprotection.

The World Health Organization (WHO) estimates that as much as 80% of the solar radiation that an adult receives throughout his/her life is received during the first 18 years (1). Skin protection against harmful solar radiation during this early stage of life is therefore a highly important factor in the prevention of future skin-related diseases. In this respect, recent developments in pediatric dermatology and cosmetic technology have led to remarkable improvements in child skin protection products. However, in spite of these scientific breakthroughs, many currently available commercial sunscreen formulations have not been well received by the general public, due to inadequate sensory properties, chemical instability, undesirable side effects, and low effectiveness. These disadvantages are not only attributable to the formulations themselves, active principle, and excipients, but also, to a large extent, galenic aspects. The objective of this work was to develop and characterize a sunscreen emulsion for pediatric use, using a towelette as vehicle, to overcome problems of ineffectiveness and formulation instability, and to improve skin-sensory properties. The composition of the towelette, the emulsion, and the presentation format were selected on the basis of the differences between children's and adult skin. In order to evaluate the chemical stability of the formulation, a study of the organoleptic, physicochemical, microbiological, and rheological characteristics was carried out at 4°, 25°, and 40°C over a period of 30 days. Tests were performed on both the sunscreen emulsion only and the same formulation impregnated within a towel, to test the influence the towel may have on the stability of the emulsion.

Potential applications of CRISPR/Cas for next-generation biomonitoring of harmful algae blooms: A review.

Research on harmful algal and cyanobacterial blooms (HABs and CHABs) has risen dramatically due to their increasing global distribution, frequency, and intensity. These blooms jeopardize public health, ecosystem function, sustainability and can have negative economic impacts. Numerous monitoring programs have been established using light microscopy, liquid chromatography coupled to mass spectrometry (LC-MS), ELISA, and spectrophotometry to monitor HABs/CHABs outbreaks. Recently, DNA/RNA-based molecular methods have been integrated into these programs to replace or complement traditional methods through analyzing environmental DNA and RNA (eDNA/eRNA) with techniques such as quantitative polymerase chain reaction (qPCR), fluorescent in situ hybridization (FISH), sandwich hybridization assay (SHA), isothermal amplification methods, and microarrays. These have enabled the detection of rare or cryptic species, enhanced sample throughput, and reduced costs and the need for visual taxonomic expertise. However, these methods have limitations, such as the need for high capital investment in equipment or detection uncertainties, including determining whether organisms are viable. In this review, we discuss the potential of newly developed molecular diagnosis technology based on Clustered Regularly Interspaced Short Palindromic Repeats/Cas proteins (CRISPR/Cas), which utilizes the prokaryotic adaptative immune systems of bacteria and archaea. Cas12 and Cas13-based platforms can detect both DNA and RNA with attomolar sensitivity within an hour. CRISPR/Cas diagnostic is a rapid, inexpensive, specific, and ultrasensitive technology that, with some further development, will provide many new platforms that can be used for HABs/CHABs biomonitoring and research.

Safety of anti-CGRP monoclonal antibodies in patients with migraine during the COVID-19 pandemic: Present and future implications.

BACKGROUND AND OBJECTIVE: CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. METHODS: This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. RESULTS: We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P=.320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. CONCLUSION: Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.