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Tregs that lacks exon 2, also failed to induce the development of suppressor T cells. Moreover, when FOXP3 and FOXP3∆2 were simultaneously overexpressed, although the expression of several Treg-associated cell surface markers was significantly increased, only a modest suppressive activity was induced. These data indicate that in humans, overexpression of FOXP3 alone or together with FOXP3∆2 is not an effective method to generate potent suppressor T cells in vitro and suggest that factors in addition to FOXP3 are required during the process of activation and/or differentiation for the development of bona fide Tregs.

The mal de debarquement syndrome (MdDS), a continuous feeling of swaying, rocking, and/or bobbing, generally follows travel on the sea. The associated symptoms cause considerable distress. The underlying neural mechanisms are unknown, and to date there have been no effective treatments for this condition. Results in monkeys and humans suggested that MdDS was caused by maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation. We studied 24 subjects with persistent MdDS (3 males, 21 females; 19.1 ± 33 months). Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test. We posited that the maladapted rocking and the physical symptoms could be diminished or extinguished by readapting the VOR. Subjects were treated by rolling the head from side-to-side while watching a rotating full-field visual stimulus. Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year. Six were initially better, but the symptoms recurred. One subject did not respond to treatment. Thus, readaptation of the VOR has led to a cure or substantial improvement in 70% of the subjects with MdDS. We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS, and that the symptoms can be reduced or resolved by readapting the VOR.

His research interests include molecular epidemiologic studies on viral and bacterial diseases. References 1. World Health Organization. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV) [cited 2020 Feb 18]. https://www.who.int/news-room/detail/30-01-2020statement-on-the-second-meeting-of-the-internationalhealth-regulations-(2005)-emergency-committee-regardingthe-outbreak-of-novel-coronavirus-(2019-ncov) 2. Zhu N,

The mal de debarquement syndrome (MdDS) is a movement disorder, occurring predominantly in women, is most often induced by passive transport on water or in the air (classic MdDS), or can occur spontaneously. MdDS likely originates in the vestibular system and is unfamiliar to many physicians. The first successful treatment was devised by Dai et al. (1), and over 330 MdDS patients have now been treated. Here, we report the outcomes of 141 patients (122 females and 19 males) treated 1 year or more ago. We examine the patient’s rocking frequency, body drifting, and nystagmus. The patients are then treated according to these findings for 4–5 days. During treatment, patients’ heads were rolled while watching a rotating full-field visual surround (1). Their symptom severity after the initial treatment and at the follow-up was assessed using a subjective 10-point scale. Objective measures, taken before and at the end of the week of treatment, included static posturography. Significant improvement was a reduction in symptom severity by more than 50%. Objective measures were not possible during the follow-up because of the wide geographic distribution of the patients. The treatment group consisted of 120 classic and 21 spontaneous MdDS patients. The initial rate of significant improvement after a week of treatment was 78% in classic and 48% in spontaneous patients. One year later, significant improvement was maintained in 52% of classic and 48% of spontaneous subjects. There was complete remission of symptoms in 27% (32) of classic and 19% (4) of spontaneous patients. Although about half of them did not achieve a 50% improvement, most reported fewer and milder symptoms than before. The success of the treatment was generally inversely correlated with the duration of the MdDS symptoms and with the patients’ ages. Prolonged travel by air or car on the way home most likely contributed to the symptomatic reversion from the initial successful treatment. Our results indicate that early diagnosis and treatment can significantly improve results, and the prevention of symptomatic reversion will increase the long-term benefit in this disabling disorder.

1. Monkeys received optokinetic stimulation at 60 degrees/s about their yaw (animal vertical) and pitch (animal horizontal) axes, as well as about other head-centered axes in the coronal plane. The animals were upright or tilted in right-side-down positions with regard to gravity. The stimuli induced horizontal, vertical, and oblique optokinetic nystagmus (OKN). OKN was followed by optokinetic after-nystagmus (OKAN), which was recorded in darkness. 2. When monkeys were tilted, stimulation that generated horizontal or yaw axis eye velocity during OKN induced a vertical or pitch component of slow phase velocity during OKAN. This has been designated as "cross-coupling" of OKAN. Eigenvalues and eigenvectors associated with the system generating OKAN were found as a function of tilt. They were determined by use of the Levenberg-Marquardt algorithm to minimize the mean square error between the output of a model of OKAN and the data. 3. The eigenvector associated with yaw OKAN (yaw axis eigenvector) was maintained close to the spatial vertical regardless of the angle of tilt. The eigenvector associated with pitch OKAN (pitch axis eigenvector) was always aligned with the body axis. The data indicate that velocity storage can be modeled by a piecewise linear system, the structure of which is dependent on gravity and the yaw axis eigenvector, which tends to align with gravity. 4. Yaw axis eigenvectors were also determined by giving optokinetic stimulation about head-centered axes in the coronal plane with the animal in various angles of tilt. A technique using a spectral analysis of residuals was developed to estimate whether yaw and pitch OKAN slow phase velocities decayed concurrently at the same relative rate and over the same time course. The eigenvectors determined by this method were in agreement with those obtained by analyzing OKAN elicited by yaw OKN. 5. During yaw OKN with the animal in tilted positions, the mean vector of the ensuing nystagmus was closer to the body axis than to the spatial vertical. This suggests that there is suppression of the cross-coupled pitch component during OKN. The direction of the stimulus may be utilized to suppress components of velocity storage not coincident with the direction of stimulus motion. 6. There were similarities between the monkey eigenvectors and human perception of the spatial vertical, and the mean of eigenvectors for upward and downward eye velocities overlay human 1-g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS)

The static ocular torsional position of both eyes of 23 patients was measured by means of fundus photographs one day before and one week after unilateral vestibular neurectomy for the treatment of acoustic neuroma, Ménière's disease or paroxysmal vertigo. The results showed that in all patients the vestibular neurectomy caused both eyes to tort (i.e. to roll around the visual axis) toward the side of the neurectomy when measured one week after operation. The extent of this torsion was an average of 9.5 degrees one week after operation and there was no statistically significant difference in the average magnitude of the torsion in the two eyes. In 8 of these patients, additional measurements were made at intervals up to one year after operation and it was found that in these patients there is a significant reduction in torsion over time from an average of 10.2 degrees one week after operation to an average of 2.8 degrees by 16 weeks after operation. The change in torsional eye position following the neurectomy was accompanied by a change in the perceived visual orientation of a small (9.5 degrees visual angle) illuminated horizontal line at a straight ahead eye level position in an otherwise completely darkened room. One week after operation when asked to adjust the line to the perceived gravitational horizontal by rotating it in roll (i.e. around an X axis), patients who had had a right vestibular neurectomy consistently set the line so that the right side of the line (from the patient's point of view) was below the true gravitational horizontal. Similarly patients after a left neurectomy consistently set the line so that the left side of the line was below the true gravitational horizontal. There is a high correlation (r = 0.95) between the direction and magnitude of the change in torsional eye position and the direction and magnitude of the change in the perceived visual horizontal one week after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

IntroductionMal de Debarquement Syndrome (MdDS) is a neurological condition typically characterized by a sensation of motion, that persists longer than a month following exposure to passive motion (e.g., cruise, flight, etc.). The most common form of MdDS is motion triggered (MT). However, recently it has been acknowledged that some patients develop typical MdDS symptoms without an apparent motion trigger. These cases are identified here as spontaneous or other onset (SO) MdDS. This study aimed to address similarities and differences between the MdDS subtypes. Diagnostic procedures were compared and extensive diagnostic guidelines were proposed. Second, potential triggers and associated psychological components of MdDS were revealed.MethodsThis was a retrospective online survey study for MT and SO MdDS patients. Participants were required to respond to a set of comprehensive questions regarding epidemiological details, as well as the diagnostic procedures and onset triggers.ResultsThere were 370 patients who participated in the surveys. It is indicated that MdDS is often misdiagnosed; more so for the SO group. In addition to the apparent self-motion, both groups reported associated levels of stress, anxiety and depression.DiscussionIt appears at present that both MdDS subtypes are still poorly recognised. This was the first attempt to evaluate the diagnostic differences between MdDS subtypes and to propose a set of comprehensive diagnostic guidelines for both MdDS subtypes. In addition, the current research addressed that associated symptoms such as stress, anxiety and depression should also be considered when treating patients. We hope this study will help the medical community to broaden their awareness and diagnostic knowledge of this condition.Electronic supplementary materialThe online version of this article (10.1007/s00415-017-8725-3) contains supplementary material, which is available to authorized users.