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Objective: To evaluate the long-term effectiveness, safety, and tolerability of erenumab in a real-world migraine population, looking for putative predictors of responsiveness. Background: Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long-term extension studies of double-blind, placebo-controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. Methods: A 48-week, multicenter, longitudinal cohort real-life study was conducted at 15headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high-frequency episodic migraine (HFEM) or CM aged 18–65years. Each patient was treated with erenumab 70mg, administered monthly. The dose was switched to 140mg in nonresponders and in responders who had become nonresponders for at least 4weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test-6 scores (HIT-6) during the same time interval. Results: A total of 242 patients with migraine received at least one dose of erenumab 70mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3migraine-preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3±5.3(mean±SD) in patients with HFEM, and MHD by 12.8±8.9 (mean±SD) in subjects with CM. VAS and HIT-6scores were decreased by 1.8±1.9 (mean±SD) and 12.3±11 (mean±SD) in HFEM, and by 3.0±2.2 (mean±SD) and 13.1±11.2 (mean±SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p=0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p=0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p=0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p=0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p=0.004). Conclusions: Long-term (48-week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real-life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.

Objective: This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work-related disability in migraine patients and the steps devoted to this aim. Background: Episodic and chronic migraine (EM and CM) constitute an enormous economic burden to societies, and the vast majority of this burden is attributable to indirect costs, ie those associated with productivity loss. A measure of work-related disability is therefore needed to quantify the impact of EM and CM on patients' ability to carry out work tasks. Methods: We briefly present the advantages and disadvantages of the disability measures that have been most commonly used for this purpose and the rationale for developing a new measure. Results: The entire process of development of HEADWORK, a questionnaire designed to assess work-related disability, is presented together with short-term sensitivity to change. Conclusions: Current headache disability measures need improvement. HEADWORK is a valid, reliable, and sensitive questionnaire to address the amount and severity of work-related difficulties and of the factors contributing to such difficulties. HEADWORK is suitable for daily clinical practice, epidemiological research and for clinical trials, and potentially to define work-related disability weights for the calculation of migraine indirect costs.

Fungi are ecologically ubiquitous organisms on earth and regarded as one of the prolific sources of natural products. Fungal endophytes may provide essential prerequisite molecules to plant biochem...

Objective The Bologna motor and non-motor prospective study on parkinsonism at onset (BoProPark) was designed to prospectively characterize motor and non-motor features in patients with a progressive neurodegenerative disease starting with parkinsonism since early disease stage and to investigate their diagnostic and prognostic role in the differential diagnosis of Parkinson’s disease from atypical parkinsonisms. The aim of this paper is to describe the method and population of the BoProPark study. Methods Patients referred to our Department with parkinsonism within 3 years from motor onset were recruited. Secondary causes of parkinsonism were excluded. Each patient underwent a comprehensive evaluation of motor and non-motor symptoms, assessed by means of quantitative, objective instrumental tests in addition to scales and questionnaires. The evaluations were performed at enrolment (T0), after 16 months (T1) and after 5 years (T2). Diagnoses were made according to consensus criteria. Results We recruited 150 patients, with mean age 61.5 ± 9.8 years and mean disease duration 20 ± 9 months. H&Y stage was 1 in 47.3% and 2 in 46.7% of cases. Mean UPDRS-III was 17.7 ± 9.2. Fifty-four patients were on dopaminergic treatment with median levodopa equivalent daily dose (LEDD) of 200 mg. Conclusions We expect that the prospective nature of the BoProPark study as well as the comprehensive, instrumental evaluation of motor and non-motor symptoms in patients with parkinsonism will provide important new insights for both clinical practice and research. Our data could be used for comparison with other cohorts and shared with national and international collaborators to develop new innovative projects.

Microalgae-based biofuel is considered as one of the most promising sources of alternative energy because it is sustainable and does not pose threats to the environment and food security. However, attempts in improving microalgal strains to attain the ideal characteristics for biofuel application are yet to unravel. In this study, random UV-C mutagenesis was employed to generate starch-deficient mutants of indigenous Chlorella vulgaris to enhance its productivity. Out of 872 colonies, two isolated mutants (cvm5 and cvm6) were isolated and showed significant increase in cell concentrations by > 1.47-fold and > 1.04-fold, respectively. However, mutant cells exhibited smaller in size which might contributed to the significant decrease in their biomass. Moreover, gathered data revealed that the total lipid content of cvm5 was enhanced significantly (75%, > 1.3-fold increase). Additionally, triacylglycerol (TAG) content of the said mutant constitutes 48% of the dry cell weight (DCW) while cvm6 consist of 41% of the DCW. These promising and novel findings suggest that the two generated and isolated mutants are good candidates for future commercial biofuel production, especially in the Philippines. In addition, these findings may contribute on the prior knowledge of the usage of UV-C for microalgal strain development.

A wide range of probiotic products is available on the market and can be easily purchased over the counter and unlike pharmaceutical drugs, their commercial distribution is not strictly regulated. In this study, ten probiotic preparations commercially available for children&rsquo, s consumption in the Republic of the Philippines (PH) and the Republic of Korea (SK) have been investigated. The analyses included determination of viable counts and taxonomic identification of the bacterial species present in each formulation. The status of each product was assessed by comparing the results with information and claims provided on the label. In addition to their molecular identification, safety assessment of the isolated strains was conducted by testing for hemolysis, biogenic amine production and antibiotic resistance. One out of the ten products contained lower viable numbers of recovered microorganisms than claimed on the label. Enterococcus strains, although not mentioned on the label, were isolated from four products. Some of these isolates produced biogenic amines and were resistant to one or several antibiotics. Metagenomic analyses of two products revealed that one product did not contain most of the microorganisms declared in its specification. The study demonstrated that some commercial probiotic products for children did not match their label claims. Infants and young children belong to the most vulnerable members of society, and food supplements including probiotics destined for this consumer group require careful checking and strict regulation before commercial distribution.

Background The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration ClinicalTrials.gov identifier: NCT02686034.

Fungi are ecologically ubiquitous organisms on earth and regarded as one of the prolific sources of natural products. Fungal endophytes may provide essential prerequisite molecules to plant biochemical pathways which allow the efficient synthesis of primary and secondary metabolites. This study characterized the influences of various combinations of process parameters namely, carbohydrate, nitrogen, and phosphorus sources on citric acid (CA) production by the isolated fungal endophyte

A wide-range investigation of the microbiological quality of fresh produce from different open air markets and supermarkets in Luzon, Philippines was performed. Different vegetables which are usually consumed raw (bell pepper, carrot, lettuce, mung bean sprout, and tomato) had been screened for the presence and amount of contamination of enteric microorganisms, namely Escherichia coli, Salmonella spp., and somatic bacteriophages (or viruses). Phenotypic characterization was employed using selective and differential media such as eosin methylene blue agar and xylose lysine deoxycholate agar. Viable plate count (colony-forming units or CFU) and most probable number (MPN) methods were used to estimate the cell numbers of E. coli and Salmonella spp., respectively. Double agar assay was used to detect and quantify somatic phages as plaque-forming units (PFU). Polymerase chain reaction was also done to confirm the identity of the isolates using species-specific primers. From a total of 410 vegetable samples collected, 44 bacterial (prevalence of 5.85% E. coli and 5.12% of Salmonella spp.) and 21 (prevalence of 5.12%) viral isolates were obtained. It is alarming to note that samples contaminated with Salmonella spp. were significantly higher in counts (3.751 ± 0.60 log MPN/g) as compared to E. coli (1.472 ± 0.25 log CFU/g), while samples with coliphage (0.316 ± 0.12 log PFU/g) were the least in numbers. The degree of contamination in the samples can cause great risks on the health of individuals especially in developing countries such as the Philippines. Thus, monitoring on the handling of different produce is important to improve the country’s food quality and safety.

Contaminated irrigation water may greatly affect not only the quality of produce but also the people exposed to it. In this study, agricultural irrigation waters in Bulacan, Philippines were assessed and found to be contaminated with Escherichia coli (E. coli) ranging from 0.58 to 4.51 log10 CFU/mL. A total of 79 isolates of E. coli were confirmed through polymerase chain reaction (PCR) amplifying the uidA gene and were tested for phenotypic resistance using 10 antimicrobials through the Kirby-Bauer disc diffusion method. Forty-six isolates (58.22%) were noted to be multidrug resistant (MDR) with high resistance rate to cephalothin, tetracycline, streptomycin, ampicillin, trimethoprim, nalidixic acid, and chloramphenicol. Moreover, this study also examined the prevalence of Class I and II integrons accounting to 67.39% and 17.39%, respectively, of the MDR E. coli strains using multiplex PCR. The results imply that the agricultural water used in Bulacan is contaminated with the fecal material of man or other animals present in the area, and the presence of MDR bacteria, which pose a potential threat to individuals in these areas, is alarming. In addition, detection of integrons could be a good marker for the identification of MDR isolates. Lastly, this study could develop strategies for the proper management of farming sites leading to the detection of food-borne pathogens and prevention of infectious diseases.