Three monthly administration of erenumab 70 mg subcutaneously.

RNA concentration was determined by absorbance at 230 and 280 nm using the NanoDrop Spectrophotometer (Euroclone Milano). Synthesis of cDNA was performed by using MirXMirna First strand Synthesis (Takara-Diatech, Jesi-An Italy) and TB Green q-Rt PCR is used (Takara-Diatech, Jesi-An Italy) to determine expression levels of miRNA-34a-5p and miRNA-382-5p. The denaturation was performed at 95°C and the amplification was performed through two-step cycling (95-60°C) for 40 cycles with a Light Cycler 480 Instrument RT-PCR Detection System (Roche, Milan, Italy). Target gene expression levels was normalized with U6 (a type of small nuclear RNA), used as housekeeping gene. Gene expression levels were calculated according to 2−∆Ct = 2 − (Ct gene − Ct housekeeping gene) formula by using Ct values.

Chronic Migraine

First injection of erenumab 70 mg subcutaneously was administered in hospital. The second injection of erenumab 70 mg was administered in hospital after 28 days, while the third and last dose of erenumab 70 mg was self-administered at home by the patients themselves after an additional 28-day interval.

Erenumab

IRCCS Mondino Foundation

Neurophysiological, Biomolecular and Psychological Aspects of Erenumab Treatment in Chronic Migraine

Neurophysiological, Biomolecular and Psychological Aspects of Erenumab Treatment in Chronic Migraine: an Open Label, Hypothesis Generator Study

Measured by the temporal summation threshold (TST) of the nociceptive withdrawal reflex

Measured by the single stimulus reflex threshold (RTh) of the nociceptive withdrawal reflex.

Migraine-related disability as measured by MIDAS test: 0-5 (grade I): minimal disability, 6-10 (grade II): mild disability, 11-20 (grade III): moderate disability, 21-40 (grade IVa): severe disability, 41 and higher (grade IVb): very severe disability.

Migraine-related disability as measured by HIT-6 test: 49 or less: no impact, 50-55: some impact, 56-59: substantial impact, 60-78 severe impact.

Migraine-related disability as measured by ASC-12 test: 0-2: none; 3-5: mild; 6-8: moderate; 9 or more: severe.

Quality of life measured by MSQ. 14-item assessment, with each item rated on a 6-point scale (ranging from "none of the time" to "all of the time"). We evaluated 3 scores, namely Role Function-Restrictive (RR), Role Function- Preventive (RP), and Emotional Function (EF). Raw scores have been transformed to a 100-point scale, with higher scores indicating better quality of life.

Quality of life measured by SF-36. 36-item assessment that gives us information about 8 different domains: physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items)

Psychological state as measured by HADS. a 14-items questionnaire on a 4-point (0-3) Likert scale assessing symptoms of anxiety and depression. A score of 8 or higher in the two different domains is considered significant for anxiety and/or depression;

Psychological state measured by LDQ. It is a self-completion 10-item instrument to measure dependence upon a variety of substances. No cut-off score indicative of dependence has been established

Psychological state measured by TAS-20. It is a 20-item questionnaire on a 5-point (1-5). Likert scale assessing alexithymia traits, i.e., individuals' difficulty in expressing their own feelings in words. A score of 61 or higher was considered significant for the presence of alexithymia.

Measured by percentage of patients with a reduction in migraine days of a least 30% (30% Responder).

Measured by percentage of patients with a reduction in migraine days of a least 50% (50% Responder).

IRCCS National Neurological Institute "C. Mondino" Foundation

Since PBMCs contain the full complement of epigenetic enzymes found in most tissues, the investigators evaluated the role of DNA methylation in the regulation of ES gene transcription in all the enrolled subjects. DNA was extracted from whole blood using QIAmp DNA Blood Mini Kit and its concentration was determined by NanoDrop quantification. Arrays preparation and data analysis were performed by Genomix4Life srl. High-quality DNA (500 ng) was bisulfite converted using EZ DNA methylation kit. Bisulfite converted DNA (200ng) was used for analysis of whole-genome methylation, using the HumanMethylation 450 K BeadChip, which contains 485 577 probes covering 21 231 (99%) RefSeq genes.

Ircss Mondino Foundation

Gene Expression of Endocannabinoid System in Episodic and Chronic Migraine Patients

Peripheral Gene Expression of Endocannabinoid System Components in Episodic and Chronic Migraine Patients: a Pilot Study

CB1 protein expression in the peripheral blood mononuclear cells (PBMCs)

CB2 protein expression in the peripheral blood mononuclear cells (PBMCs)

Gene expression of the endocannabinoid receptors in the peripheral blood mononuclear cells ( PBMCs)

Gene expression of the FAAH in the peripheral blood mononuclear cells ( PBMCs)

Gene expression of the NAPE-PLD in the peripheral blood mononuclear cells ( PBMCs)

Gene expression of the DAGL in the peripheral blood mononuclear cells ( PBMCs)

Gene expression of the MAGL in the peripheral blood mononuclear cells ( PBMCs)

DNA methylation in the regulation of ES gene transcription

Ministry of Health, Italy

60 day oral administration of sugar placebo twice per day before lunch and supper.

60 day oral administration of active study drug (methylphenidate) twice per day before lunch and supper.

Obesity

60 days on oral methylphenidate administered 2 times daily before lunch and supper.

60 days on oral placebo administered 2 times daily before lunch and supper

Placebo

Children's Hospital Of Eastern Ontario Research Institute

University of Ottawa

The Effects of Methylphenidate on Energy Intake and Energy Expenditure

The Effects of Methylphenidate on the Reduction of Food Energy Intake and on the Augmentation of Energy Expenditure

Participant will be offered a lunch buffet that includes items they indicate are preferred. They will be able to eat as much or as little as they choose.

Indirect calorimetry measure: participant lies supine on a bed while a neoprene mask is attached to their face. Expired breath is captured by the metabolic cart to assess resting energy expenditure and the thermic effect of feeding.

Participant stands next to a stadiometer; height will be used to determine BMI at baseline.

This measure is a conglomerate of body weight (kg) divided by height (meters squared)

A "go/no-go"computer task that measures reaction time to food and non-food cues with simple button-presses on a keyboard.

Odourized pens, called Sniffin Sticks, are used to measure odour detection threshold for a non-toxic odourant called n-butanol.

We have not made a plan to make IPD available. We do plan on publishing the findings, but as per normal scientific reporting, with deidentified data.

Phillippe Robaey

Qualified Investigator, MD, PhD, FRCPC

Children's Hospital of Eastern Ontario

Preinduction with isosorbide dinitrate gel solution (80 mg/1.5 mL) were administered in the posterior fornix every 3 hours. Once a Bishop score of over 7 was reached, oxytocin was infused in a balanced electrolyte solution beginning with an infusion rate of 2 milli-International Units per minute (mIU/min) and doubling the dose every 15 minutes.
If the cervical conditions (<7 Bishop Score) did not change after the treatment application, a new dose, without exceeding 4 doses, to facilitate cervical ripening.

Preinduction with misoprostol gel solution (100 mcg/1.5 mL) were administered in the posterior fornix every 3 hours. Once a Bishop score of over 7 was reached, oxytocin was infused in a balanced electrolyte solution beginning with an infusion rate of 2 milli-International Units per minute (mIU/min) and doubling the dose every 15 minutes.
If the cervical conditions (<7 Bishop score) did not change after the treatment application, participants received a new dose, without exceeding 4 doses, to facilitate cervical ripening.

Cervical Pregnancy

Maternal Care for Late Fetal Death

Isosorbide Dinitrate

Misoprostol

Oxytocin was infused in a balanced electrolyte solution beginning with an infusion rate of 2 milli-International Units per minute (mIU/min) and doubling the dose every 15 minutes.

acetic acid/huvudvärk

Neurophysiological, Biomolecular and Psychological Aspects of Erenumab Treatment in Chronic Migraine

Gene Expression of Endocannabinoid System in Episodic and Chronic Migraine Patients

The Effects of Methylphenidate on Energy Intake and Energy Expenditure

Medical Management of Late Intrauterine Death.

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