Background: Acupuncture can be used in clinical practice to promote motor recovery in patients with acute ischemic stroke and paralysis. It is an economical, safe, and effective method that can be easily implemented in clinical settings. However, although scalp acupuncture is an easy-to-perform micro-needle therapy, its efficacy in the treatment of hemiplegia resulting from acute ischemic stroke remains disputed. Methods/Design: This is a randomized parallel-controlled single-blind trial. It will be performed at the Department of Neurology, Second Hospital, Lanzhou University, China. Seventy-two patients suffering from acute ischemic stroke with paralysis will be randomly assigned to undergo 14 days of either conventional drug treatment (control group) or conventional drug treatment combined with scalp acupuncture that uses the twirling-needle method (once a day, 6 consecutive days followed by 1 day off per week). The primary outcome is the difference in National Institutes of Health Stroke Scale (NIHSS) scores between just after the stroke and 14 days after treatment. Secondary outcomes include motor recovery (assessed by the Fugl-Meyer Motor Scale) and activities of daily living (assessed by the Barthel index). Discussion: Objectively evaluating the efficacy of twirling-needle scalp acupuncture in the treatment of hemiplegia after acute ischemic stroke will provide evidence for assessing whether this method can improve motor recovery from hemiplegia resulting from acute ischemic stroke. Trial registration: This trial has been registered on 11 March 2016 in the Chinese Clinical Trial Registry (registration number: ChiCTR-IOR-16008083). Ethics: This trial has been approved by Ethics Committee, Second Hospital, Lanzhou University of China (approval number: 2016A-003) and will be performed in accordance with the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Written informed consent will be obtained from the patients and their relatives.

Background: Migraine is a global disease with a high morbidity rate, and while there is medication for migraine prevention, it has many side effects. Thus there is a need to find a non-drug therapy to prevent migraine in patients with frequent attacks of migraine, severe pain, and poor drug control. Cortical spreading depression (CSD) is an important pathological mechanism behind migraine. Electrical fastigial nucleus stimulation (FNS) can reportedly inhibit the occurrence and propagation of CSD, and therefore can be used to prevent migraine. Methods/Design: This is a prospective, multi-center, randomized, double-blind, sham-controlled trial. It will be performed at Chengdu Second People's Hospital, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Fourth People's Hospital, the First Affiliated Hospital of Chongqing Medical University, and Chongqing People's Hospital, China. The approach is to randomly allocate 80 eligible migraine patients to undergo 3 months of either noninvasive electrical FNS (pulse width 90 μs, frequency 1.8 kHz, and output current 10 mA) or ineffective sham-stimulation (using the same stimulation equipment; pulse width 90 μs, frequency 10 kHz, and output current 0.18 mA). The primary outcomes are: change in monthly migraine days between the run-in month and 3 ^rd month of treatment, and percentage of patients having at least a 50% reduction of monthly migraine days in the 3 ^rd month of treatment. The secondary outcomes are: change between average monthly migraine days across 3 months of treatment and monthly migraine days in the 3 ^rd month of treatment, Visual Analogue Scale score in the 3 ^rd month of treatment, change in monthly anti-migraine drug use between the run-in month and 3 ^rd month of treatment, migraine disability assessment questionnaire score, accompanying symptoms, and adverse reactions. Discussion: In previous studies on electrical FNS for the treatment of various brain injuries, sample sizes have been small with inclusion of only a small number of institutions and non-rigorous trial protocols. Accordingly, the data obtained were not very reliable. In this study, we will validate the efficacy of electrical FNS in migraine prevention using a multi-center, randomized, double-blinded, controlled trial. Our findings will provide evidence for clinical application of this method. Trial registration: The trial protocol was registered at Chinese Clinical Trial Registry (www.chictr.org.cn) (registration number: ChiCTR-ICR-15006273) on 5 April 2015. Ethics: This trial was approved by the Ethics Committee of Chengdu Second People's Hospital, China on 9 April 2015 (approval number: 2015010), and will be performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Written informed consent will be obtained from participants or their guardians.

Background: Short-duration cognitive behavioral therapy is an effective method for the treatment of obsessive-compulsive disorder. It alters the functions of multiple brain regions or tissues, and improves symptoms. Imaging studies show changes in the microstructure of white matter fiber bundles of patients with obsessive-compulsive disorder. Methods/Design: We will conduct a single-blind, parallel, controlled trial in the Beijing Anding Hospital, Capital Medical University, China. A cohort of 60 patients with obsessive-compulsive disorder will undergo 12 weeks of cognitive behavioral therapy. An additional 60 healthy controls will comprise the control group. All participants will be evaluated before and after 12 weeks of treatment. The primary outcome will be fractional anisotropy values in the frontal-striatal-thalamic circuits assessed by diffusion tensor imaging. The secondary outcomes will be Yale-Brown Obsessive-Compulsive Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Scale scores. Discussion: This trial will assess the changes in white matter fibers of patients with obsessive-compulsive disorder after treatment with cognitive behavioral therapy using diffusion tensor imaging. This will hopefully reveal the neural mechanisms underlying the treatment of obsessive-compulsive disorder by cognitive behavioral therapy. It will also provide objective clinical evidence of its effectiveness, and for the development of individual treatment strategies. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) (ChiCTR-IOR-14005436) on 29 October 2014. Ethics: The study protocol was approved by the Ethics Committee of Beijing Anding Hospital of Capital Medical University of China on 17 June 2013, approval number (2013)Keyan(7). Informed consent: Written informed consent will be provided by participants and their guardians.

Background: Conventional mechanical ventilation often leads to lung inflammatory responses and oxidative stress, influencing a patient's prognosis. Lung protective ventilation has been widely used during one-lung ventilation and abdominal surgeries as it can reduce lung tissue injury and improve systemic oxygenation. However, there are few reports on its use during craniotomy. Methods/Design: This multi-center, randomized, parallel, controlled trial will be performed at Anhui Provincial Hospital (Southern District), and the Renmin Hospital of Wuhan University, China. Sixty patients scheduled to undergo craniotomy and meeting our eligibility criteria will be randomly allocated to undergo either lung protective ventilation (6 mL/kg tidal volume, 10 cmH ₂ O positive end-expiratory pressure, respiratory frequency 15 breaths/min; n = 30) or conventional mechanical ventilation (10 mL/kg tidal volume, respiratory frequency 12 breaths/min; n = 30). All patients will be evaluated from just prior to surgery (at changing of the ventilation mode) to immediately after extubation. The primary outcome measure will be dynamic lung compliance. The secondary outcome measures will be respiratory index, mean airway pressure, plateau pressure, alveolar and plasma markers of inflammation, and oxidative stress. Discussion: The outcomes will reveal the effects of a protective ventilation strategy using low tidal volumes and the use of positive end-expiratory pressure on respiratory status, postoperative pulmonary and systemic inflammation, and oxidative stress in patients undergoing craniotomy. This will provide objective evidence for the safety of protective ventilation during craniotomy. Trial registration: This trial was registered at Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-16008029) on 1 March 2016. Ethics: The study protocol was approved by the Ethics Committee of Anhui Provincial Hospital, China (approval number: 2014-59) on 27 November 2014 and will be performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Written informed consent will be obtained from participants or their guardians.

Background: Scalp block is a selective nerve block technique to inhibit the afferent input from nerves that innervate the scalp, including supratrochlear, supraorbital, zygomaticofacial, and zygomaticotemporal nerves for the anterior scalp. The greater and lesser occipital nerves innervate the posterior scalp. Methods/Design: This study is a prospective, randomized, double-blind, placebo-controlled trial, which will be performed to examine the benefits of a pre-incisional anterior scalp block with 0.5% bupivacaine in adult patients who are scheduled for supratentorial craniotomy to remove tumor. Primary outcome will be the difference of intraoperative fentanyl consumption between patients who receive anterior scalp block with 0.5% bupivacaine and those who receive normal saline solution administration. Secondary outcomes will be the hemodynamic changes from preoperative baseline at a skull pin insertion and the time from the end of surgery to successful extubation. Discussion: Skull pin insertion is known as the strongest stimulus prior to craniotomy. The results from previous studies are inconclusive regarding the advantage of scalp block as a pre-emptive analgesic technique. This study will fill this knowledge gap, and examine whether this technique is worth performing as a standard technique. Trial registration: ClinicalTrials.gov identifier: NCT02057367; registered in February 2014. Ethics: This study protocol was approved by the Ethics Committee of Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University, Thailand (approval number: ANE-2556-01510) and will be performed in accordance with the Declaration of Helsinki. Informed consent: Written informed consent will be obtained from participants prior to inclusion in this study.

Background: Studies have demonstrated the efficacy of laughter in contributing to a better quality of life. Strategies can be optimized to elevate tolerance to pain and to combat stress, thereby reducing the impacts of stress, such as the increase in arterial tension, reduction in perfusion of the non-motor organs, an increase in cellular metabolism, and a greater risk of infections. Despite the increased interest in this topic, there is still a need for more research, because many of such studies are limited by diverse methodological problems, such as lack of objective evaluations, clear distinction between laughter and humor, and establishment of dosage of the therapies (frequency and time). The objective of the current study is to determine the efficacy of spontaneous laughter in improving the post-operative prognosis for pediatric patients after minor surgery. Post-operative pain will be evaluated by the Visual Analog Scale, and urinary cortisol levels, duration of hospital stay, and anxiety by the State-Trait Anxiety Inventory for Children. Methods/Design: The study will be an open, randomized controlled trial, having three parallel arms: conventional post-operative management with analgesics; a second control group consisting of conventional treatment with an accompaniment that does not induce laughter; and an experimental group based on conventional treatment plus laughter therapy. Pediatric patients (6-14 years of age; n = 70 per group), hospitalized for minor surgery in a Mexico City hospital, will be randomly assigned to one of the three groups. Generalized linear models will be constructed to determine the adjusted effects of laughter therapy on the intensity of pain, anxiety, and duration of hospital stay. Discussion: To the best of our knowledge, no clinical trial to determine the effect of laughter therapy exists in which the effect of the vehicle is controlled. Here, we controlled this potential confounding factor by establishing a control group "accompaniment without laughter". As a secondary outcome variable, measurement of urinary cortisol levels will provide objective evidence to complement the subjective measurement of the pain as perceived by the patient. As a co-variable, the duration of effective laughter will provide greater robustness to this study. Trial registration: This trial was registered at ClinicalTrials.gov (identifier: NCT02563587) on 28 September 2015. Informed consent: The research protocol of this study has been approved by the Ethics Committee of the Hospital General Naval de Alta Especialidad de la Secretaría de Marina de la Armada de México (approval number: 076). This research adheres to the guidelines set forth in the NORMA Oficial Mexicana NOM-012-SSA3-2012 and in the Declaration of Helsinki.

Most of studies on leprosy mainly focus on its somatic symptoms. There are few reports on evaluation of cardiac autonomic status by QTc interval. We performed a cross-sectional, case-control study to investigate the QTc (QT corrected for heart rate) interval difference between leprosy patients and healthy controls. Thirty leprosy patients and 30 age- and sex-matched healthy controls were included in this study. These leprosy patients, aged 41 years on average, suffered from leprosy for an average of 4 years. 55% of these patients had more than 10 skin patches, 66% of them had somatic neuropathy, and 33% of them had cardiac autonomic neuropathy. Electrocardiogram recording from lead II showed that QTc interval was significantly longer in patients with leprosy than in healthy controls (OR: 6, 95% CI: 1.17-30.72, P = 0.03). QTc interval was unrelated to age and duration of disease and it would not be influenced by the type of neuropathies and skin symptoms. QTc results revealed that patients with leprosy had a significantly higher risk for cardiac autonomic neuropathy than healthy controls.

The pharmaceutical industry has been facing tremendous challenges in recent years. Its Research & Development activities for innovation and drug development have significantly slowed down. Researchers in academic institutions often collaborate with pharmaceutical companies by providing them with new innovative products. However, the type of funding that they normally have access to does not ease drug development beyond discovery level. Here is a list of seven alternative opportunities that may help scientists, in North America, Europe and Asia, developing further their products and overcoming the so-called "Valley of Death". This may contribute bridging the gap between them and what Big Pharma is looking for, especially for the development of central nervous system products.