Analysis of spontaneous speech in Parkinson's disease by natural language processing.

INTRODUCTION: Patients with Parkinson's disease (PD) encounter a variety of speech-related problems, including dysarthria and language disorders. To elucidate the pathophysiological mechanisms for linguistic alteration in PD, we compared the utterance of patients and that of healthy controls (HC) using automated morphological analysis tools. METHODS: We enrolled 53 PD patients with normal cognitive function and 53 HC, and assessed their spontaneous speech using natural language processing. Machine learning algorithms were used to identify the characteristics of spontaneous conversation in each group. Thirty-seven features focused on part-of-speech and syntactic complexity were used in this analysis. A support-vector machine (SVM) model was trained with ten-fold cross-validation. RESULTS: PD patients were found to speak less morphemes on one sentence than the HC group. Compared to HC, the speech of PD patients had a higher rate of verbs, case particles (dispersion), and verb utterances, and a lower rate of common noun utterances, proper noun utterances, and filler utterances. Using these conversational changes, the respective discrimination rates for PD or HC were more than 80%. CONCLUSIONS: Our results demonstrate the potential of natural language processing for linguistic analysis and diagnosis of PD.

Clinico-imaging features of subjects at risk of Lewy body disease in NaT-PROBE baseline analysis.

Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients with Parkinson's disease and dementia with Lewy bodies. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥2 prodromal symptoms (dysautonomia, hyposmia, and probable RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

Effects of MAO-B inhibitors on non-motor symptoms and quality of life in Parkinson's disease: A systematic review.

Non-motor symptoms (NMS) are common among patients with Parkinson's disease and reduce patients' quality of life (QOL). However, there remain considerable unmet needs for NMS management. Three monoamine oxidase B inhibitors (MAO-BIs), selegiline, rasagiline, and safinamide, have become commercially available in many countries. Although an increasing number of studies have reported potential beneficial effects of MAO-BIs on QOL and NMS, there has been no consensus. Thus, the primary objective of this study was to provide an up-to-date systematic review of the QOL and NMS outcomes from the available clinical studies of MAO-BIs. We conducted a literature search using the PubMed, Scopus, and Cochrane Library databases in November 2021. We identified 60 publications relevant to this topic. Overall, rasagiline and safinamide had more published evidence on QOL and NMS changes compared with selegiline. This was likely impacted by selegiline being introduced many years prior to the field embarking on the study of NMS. The impact of MAO-BIs on QOL was inconsistent across studies, and this was unlikely to be clinically meaningful. MAO-BIs may potentially improve depression, sleep disturbances, and pain. In contrast, cognitive and olfactory dysfunctions are likely unresponsive to MAO-BIs. Given the paucity of evidence and controlled, long-term studies, the effects of MAO-BIs on fatigue, autonomic dysfunctions, apathy, and ICD remain unclear. The effects of MAO-BIs on static and fluctuating NMS have never been investigated systematically. More high-quality studies will be needed and should enable clinicians to provide personalized medicine based on a non-motor symptom profile.

On workdays, earlier sleep for morningness and later wakeup for eveningness are associated with better work productivity.

INTRODUCTION: Misalignment of chronotype and social schedules result in sleep and health impairments. Presenteeism, the work productivity loss caused by health problems, has much more social costs than absenteeism and is associated with sleep disturbance. However, little is known about the link between chronotype and presenteeism. In this study, the associations between chronotype, sleep schedules, presenteeism, and the mediating role of sleep disturbance were examined. METHODS: A cross-sectional survey was conducted on 8155 office workers from 42 companies in Japan, from 2017 to 2019. The participants answered self-administered questionnaires asking about presenteeism (Work Limitations Questionnaire [WLQ]), sleep disturbance (Pittsburgh Sleep Quality Index [PSQI]), and habitual sleep schedules which enable to calculate the midpoint of sleep on free days, sleep corrected (MSFsc). The mediating effect was examined by using structural equation modeling (SEM). RESULTS: The participants comprised 4462 males and 3677 females (mean age: 36.7 years), and their mean productivity loss was 5.97%. A later sleep onset (+0.29%/h), early wakeup (+0.14%/h), and eveningness (+0.27%/h, MSFsc) were associated with presenteeism in all participants; however, the effect size and significance differed depending on their chronotype. SEM demonstrated a complete mediation model between chronotype and presenteeism, mediated by sleep disturbance and adjusted by age. CONCLUSIONS: Chronotype did not directly, but indirectly affected presenteeism through sleep disturbance. Eveningness leads to sleep disturbance, which then causes presenteeism. On workdays, early sleep times for morningness people, and late wakeup times for eveningness people may improve their work productivity.

Too much is too little: Estimating the optimal physical activity level for a healthy mental state.

Introduction: Although physical activity and exercise are generally thought to have favorable effects on mental health, excessive physical activity may have unfavorable effects. In this study, the associations between physical activity and the states of mental health with U-shaped dose-response curves were hypothesized, and the ranges of physical activity resulting in optimal effects on mental health were investigated. Methods: A cross-sectional survey was conducted on 1,237 adult volunteers in 2017 and 2018. Of these volunteers, 526 participants validly answered the self-administered questionnaires asking about physical activity, depression, anxiety, resilience, insomnia vulnerability, and life events. A comparison of mental health measures by physical activity levels and quadratic equation model regressions were performed. Results: No significant linear associations between physical activity levels and mental health measurements were observed; however, the U-shaped, quadratic equation models indicated a significance. The following levels of physical activity per week optimized the mental health measurements values of the participants: 6,953 MET-minutes and 25.70 h for depression, 5,277 MET-minutes and 21.60 h for state anxiety, 5,678 MET-minutes and 22.58 h for trait anxiety, 25.41 h for resilience, and 9,152 MET-minutes and 31.17 h for insomnia vulnerability. Conclusion: Physical activities in the optimal range were associated with more favorable mental health measurements. Physical activities that were too much or too long and outside of the optimal range were associated with less favorable mental health measurements.

Instability of speech in Parkinson disease patients with subthalamic nucleus deep brain stimulation.

INTRODUCTION: The impact of deep brain stimulation (DBS) on speech rhythm and its mechanism remains unclear. We investigated speech rhythm characteristics of patients with Parkinson's disease (PD) treated with subthalamic nucleus (STN) DBS to understand the underlying pathophysiology better. METHODS: We enrolled a total of 105 participants and evaluated speech rhythm performances among patients with PD who had undergone STN-DBS (the PD-DBS group), patients with PD treated only with medication (the PD-Med group), patients with cerebellar ataxia (the CA group), and healthy controls (the HC group). Each participant was asked to repeat the syllable/pa/at a comfortable self-chosen steady pace. A widely-used software (the Motor Speech Profile) program performed an acoustic analysis. RESULTS: Compared to the PD-Med and HC groups, speech rate instability (DDKjit) was significantly higher in the PD-DBS and CA groups (p < 0.01). However, after DBS was turned off, the DDKjit of the PD-DBS group improved to a level comparable to that of the PD-Med and HC groups. In contrast to the significantly higher variability of speech volume (DDKcvi) in the CA group, the PD-DBS group showed similar DDKcvi to the PD-Med and HC groups. CONCLUSIONS: STN-DBS affects the speech rate stability of patients with PD. Speech rhythm disorders caused by STN-DBS were phenotypically similar to that in CA in terms of interval variability but different regarding amplitude variability. Further studies are warranted to elucidate the underlying pathophysiology of speech rhythm disorders in PD patients treated with DBS.

Remote Work Decreases Psychological and Physical Stress Responses, but Full-Remote Work Increases Presenteeism.

Introduction: Remote work was widely promoted in 2020, as a result of the COVID-19 pandemic. However, the effects of remote work on psychological and physical stress responses and presenteeism of workers remain unclear. This research aims to provide empirical evidence of the implications for people and organizations of this new scenario of working from home. Methods: A two-wave panel survey of before and after the pandemic was performed to investigate the effects of remote work on these aspects among office workers. A total of 3,123 office workers from 23 tertiary industries responded to a questionnaire. Participants were surveyed about their job stress conditions and sleep practices in both 2019 and 2020, who had not done remote work as of 2019 were included in the study. The effects of remote work on psychological and physical stress responses and presenteeism were analyzed by multivariate analysis, with the adjustment of age, gender, overtime, job stressors, social support, and sleep status. Results: The multivariate logistic regression analysis demonstrated that remote work was associated with the reduction of psychological and physical stress responses independently of changes of job stressors, social support, sleep disturbance, and total sleep time on workdays. On the other hand, remote work of 5 days a week (full-remote) was associated with the reduction of work productivity. Conclusion: Promoting remote work can reduce psychological and physical stress responses, however, full-remote work has the risk of worsening presenteeism. From the viewpoint of mental health, the review of working styles is expected to have positive effects, even after the end of the COVID-19 pandemic.

Longitudinal analysis of premotor anthropometric and serological markers of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder in which nonmotor symptoms, such as constipation and hyposmia, precede the onset of motor symptoms by 20 years. The aim of this study was to identify biomarkers at the premotor stage of PD. We assessed the differences in longitudinal changes in anthropometric and serological indices obtained from health check-up data before and after the onset of motor symptoms between male and female PD patients and healthy subjects. We enrolled 22 male and 23 female PD patients and 60 male and 60 female healthy controls. A mixed-effects model was used to estimate the trajectory of each clinical marker over the years before and after motor symptoms onset in the PD subjects, which were then compared with the trajectories of the healthy controls. The results showed a premotor blood pressure increase in female PD patients and premotor decreases in haematocrit, total cholesterol and low-density lipoprotein cholesterol in the male patients. Our results indicated that blood pressure, haematocrit and serum cholesterol levels are potential premotor markers of PD. Additionally, the changes in anthropometric and serological indices before PD motor symptoms onset were sex specific.

Which sleep hygiene factors are important? comprehensive assessment of lifestyle habits and job environment on sleep among office workers.

BACKGROUND: Although several lifestyle habits are associated with sleep, it is unclear which factors are important. Among office workers, the effect of job environment should also be considered. The multivariate analyses on the effects of lifestyle habits and job environment on sleep among office workers was conducted. METHODS: A cross-sectional survey of 6,342 employees from 29 companies was conducted in 2017-2019. Complete responses and informed consent were provided by 5,640 participants. The survey examined demographic variables, sleep schedules, Pittsburgh Sleep Quality Index (PSQI), Brief Job Stress Questionnaire (BJSQ), and lifestyle habits. RESULTS: Mean values were as follows: age, 36.9 years (±10.2); PSQI, 6.52 (±2.83); and total sleep time, 6h06m (±1h40m) on work days and 7h39m (±1h58m) on free days. After adjusting for job environment and demographic variables, irregular meal time (1.45-2.86), not eating vegetables every day (1.35), nightcap (2.74-3.55), weight gain (1.20-1.42), lack of sunlight in the morning in the bedroom (1.48-1.60), waking up before dawn (2.18), electronic display use in bed (1.50), and daily caffeine intake (1.27) were significantly associated with sleep disturbance. Irregular meal time (1.51-2.37), lack of morning breakfast (1.74-2.95), having dinner within 2 hours before bed time (0.49-0.64), not eating vegetables every day (1.52), lack of sunlight exposure in the morning (1.43-2.01), and caffeine use every day (1.42) were also associated with eveningness (p<.01). CONCLUSION: Each sleep hygiene factor had a different effect size. Sleep hygiene interventions to promote worker sleep health should prioritize factors in accordance with effect size.

Subjects at risk of Parkinson's disease in health checkup examinees: cross-sectional analysis of baseline data of the NaT-PROBE study.

INTRODUCTION: The present study aimed to survey the prevalence of prodromal symptoms of Parkinson's disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. METHODS: We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. RESULTS: Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p < 0.001) and ESS (9.6 ± 5.0 vs. 6.3 ± 3.2, p < 0.001), in addition to SCOPA-AUT, SAOQ, and RBDSQ. Male at-risk subjects showed lower values of hemoglobin (14.8 ± 1.3 vs. 15.0 ± 1.1, p = 0.032) and low density lipoprotein cholesterol (114.5 ± 30.3 vs. 123.0 ± 28.9, p = 0.004) than the examinees reporting no prodromal symptoms. CONCLUSION: Approximately 6% of the population aged 50 years or older was at risk for PD. Male at-risk subjects had mild hematological and metabolic changes relevant to PD.

Intraoperative Adjunctive Mitomycin C and Cryotherapy for Recurrent Conjunctival Papillary Sebaceous Carcinoma.

PURPOSE: To report a case of recurrent conjunctival papillary sebaceous carcinoma that was successfully treated by a combination of surgical resection, intraoperative topical mitomycin C application, and cryotherapy. OBSERVATIONS: A woman in her 80s developed a yellowish papillary tumor pedunculated from the surface of the upper palpebral tarsal conjunctiva in her left eye. She was histopathologically diagnosed as having sebaceous carcinoma by an excisional biopsy. We performed en bloc resection of the lateral one-third of the posterior lamella including the cutaneous margin of the upper eyelid as well as reconstruction of the defected portion by a switch-flap from the ipsilateral lower eyelid. Histopathologically, because the tumor was restricted to the epithelial region with minimal invasion into the tarsus, we diagnosed the patient to have conjunctival papillary sebaceous carcinoma. Nine months after the surgery, the tumor recurred and was resected and treated by intraoperative mitomycin C. Four months later, the tumor regrew at the resected margins and was treated by resection combined with mitomycin C and cryotherapy. After these combination treatments, the tumor did not recur for at least 1 year postoperatively. CONCLUSION AND IMPORTANCE: Although sebaceous carcinoma usually originates from the meibomian gland cells or less frequently from the Zeis or Moll gland cells, it rarely occurs from bulbar or palpebral conjunctival cells. Because sebaceous carcinoma sometimes shows a pagetoid growth pattern, it can recur even after en bloc resection with a negative study for tumor cells at the surgical margins. The recurrent sebaceous carcinoma cells showed an intraepithelial growth pattern. Considering this superficial growth property, it may be effective to apply intraoperative mitomycin C and cryotherapy treatment combined with surgical resection to reduce the possibility of recurrence of presumed conjunctival papillary sebaceous carcinoma, although mitomycin C alone seems to be insufficient as an adjunctive treatment.

[Case of posterior reversible encephalopathy syndrome caused by Fisher syndrome].

This report presents a case of a 71-year-old woman with Fisher syndrome who had posterior reversible encephalopathy syndrome (PRES) before the initiation of intravenous immunoglobulin (IVIg) treatment. She had symptoms of common cold 2 weeks before the onset of PRES. On the day of the onset, she began to stagger while walking. On day 2, she developed hypertension, vision impairment, and limb weakness and was admitted to the hospital. On day 3, she was provided steroid pulse therapy. On day 4, she developed convulsions and right imperfection single paralysis and was transferred to the our hospital. During the transfer, the patient was conscious. Her blood pressure was high at 198/107 mmHg. She had mild weakness in her limbs and face, light perception in both eyes, dilation of both pupils, total external ophthalmoplegia, no tendon reflexes, and limb and trunk ataxia. We diagnosed PRES because of the high signal intensities observed on T2-weighted MRI on both sides of the parietal and occipital lobes. We also diagnosed Fisher syndrome because of a positive anti-GQ1b immunoglobulin G antibody test and albuminocytologic dissociation in the cerebrospinal fluid. PRES showed prompt improvement with antihypertensive therapy, whereas Fisher syndrome slowly improved over a course of 2 months. This case is the first report of PRES without IVIg suggesting that Fisher syndrome induces hypertension and causes PRES.

[Treatment for paroxysmal sympathetic hyperactivity in amyotrophic lateral sclerosis patient].

We report a case of an 80-year-old man who contracted amyotrophic lateral sclerosis (ALS) 15 years ago, was put on a ventilator 8 years ago, and became locked in 3 years ago. Two years ago, he began to suffer from sudden symptoms of paroxysmal sympathetic hyperactivity (PSH) attacks (hot flushes, abnormal sweating, tachycardia, and increased blood pressure). One day, he developed multiple-organ failure. This failure healed in a few days, but PSH attacks remained. His catecholamine levels were abnormal: adrenaline, 215 pg/ml; noradrenaline, 5,960 pg/ml; and dopamine, 606 pg/ml. Diazepam was administered, which decreased both the number of PSH attacks and the catecholamine levels. When the dose was increased to 3 mg, the attacks stopped, whereas when the dose was reduced to 2 mg, the attacks relapsed. When the dose of 3 mg was continued, there was no relapse of the attacks and no re-rise in the catecholamine levels. These results show that diazepam alone has an effect on PSH attacks in ALS.

Effectiveness of levodopa treatment for diabetic chorea with reduced striatal accumulation in dopamine transporter SPECT: a case report.

We report the case of a 77-year-old woman with diabetic chorea, which presented as hemiballism of the right limbs. Initial blood examination revealed that sugar and hemoglobin A1c levels were 732 mg/dl and 12.2%, respectively. Thus, a diagnosis of hyperglycemic hyperosmolar syndrome was made at a previous hospital. Ballism of the right limbs developed after 10 days and progressively worsened. After a month, the patient was admitted to our hospital. Brain MRI (axial T1-weighted imaging) revealed a high-signal-intensity area in the left striatum. Dopamine transporter SPECT demonstrated reduced 123I-ioflupane binding in the bilateral striatum with left side predominance. Although haloperidol and risperidone were ineffective for her involuntary movement, chlorpromazine had a little effect. Levodopa and gabapentin combination treatments were effective in decreasing the symptoms. It was considered that dopamine antagonist was the medical treatment for diabetic chorea and that levodopa could worsen neurological symptoms such as chorea-ballism. However, in our case, levodopa treatment was effective.

Insights from the ganglionic acetylcholine receptor autoantibodies in patients with Sjögren's syndrome.

OBJECTIVE: It is not known whether autonomic neuropathy is a feature of Sjögren's syndrome (SS) or whether it is related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal of the present study was to investigate the autonomic dysfunction in patients with SS and the associations between autonomic dysfunction, anti-gAChR antibodies, and clinical features of SS. METHODS: (1) The first observational study tested for the presence of gAChR antibodies in the serum samples from 39 patients with SS (absent information regarding autonomic symptoms) and healthy volunteers. (2) In the second study, serological and clinical data from 10 Japanese patients diagnosed with SS were reviewed. These patients showed autonomic dysfunction, and luciferase immunoprecipitation systems (LIPS) test was conducted to detect anti-α3 and anti-ß4 gAChR antibodies. (3) In the final analysis, we combined the data of seropositive SS patients with autonomic symptom from the first study with all of the patients from the second study, and analyzed the clinical features. RESULTS: (1) The LIPS assay revealed that anti-gAChRα3 and anti-gAChRß4 antibodies were detected in the sera from patients with SS (23.1%, 9/39). Five of nine SS patients had autonomic symptoms. (2) Anti-α3 and anti-ß4 gAChR antibodies were also detected in 80.0% (8/10) of patients with SS with autonomic symptoms. Six of the ten patients were diagnosed as having SS after neurological symptoms developed. These seropositive patients had predominant and severe autonomic symptoms and were diagnosed with autonomic neuropathy. (3) Thirteen of fifteen SS patients with autonomic symptoms (86.7%) were seropositive for anti-gAChR antibodies, and we confirmed sicca complex, orthostatic hypotension, upper and lower gastrointestinal (GI) symptoms, and bladder dysfunction at high rates. CONCLUSION: The present results suggest the possibility of anti-gAChR antibodies aiding the diagnostics of SS with autonomic dysfunction.

[Cryptococcal meningoencephalitis presenting with treatable cognitive impairment and involuntary movement].

The patient is a 72-year-old Japanese woman. Seven years prior to admission, multiple nodules in her left lung were found. Bronchoscopic biopsy of the nodules did not provide a confirmative diagnosis, and probable diagnosis of cryptococcosis was made. Follow-up CT scan of the chest revealed reduction in size of the lung nodules. She was admitted to our hospital due to progressive cognitive impairment and difficulty in walking that lasted for 5 months. On admission, athetotic involuntary movement was observed in her lower extremities, predominantly in the right side. Blood and cerebrospinal fluid culture of the patient were positive for Cryptococcus neoformans. Antifungal drugs resolved the cognitive impairment, the difficulty in walking, and the involuntary movement. We assessed the cognitive impairment and observed the clinical improvement of the patient, with the use of neuropsychological examinations. To our knowledge, there has been only a few reported case of cryptococcal meningoencephalitis presenting with treatable cognitive impairment and involuntary movement.

Nose and upper lip reconstruction for purpura fulminans.

BACKGROUND: Purpura fulminans (PF) is a rare syndrome of intravascular thrombosis and haemorrhagic infarction of the skin. The initial symptom of PF is peripheral purpura which progresses to necrosis very rapidly. The prognosis of PF is poor, and the mortality is reported to be around 40%. Even if the patient survives, the patient may require amputation or reconstruction for limbs and facial necrosis. CASE REPORT: A 48-year-old male suffered from PF following a left cerebellopontine angle tumour excision. His nose and upper lip fell into necrosis afterwards. We performed nose and upper lip reconstruction at 8 months after the onset. We used a forehead flap for the nasal reconstruction and a free forearm flap for the lining. His upper lip was reconstructed with bilateral nasolabial orbicularis oris myocutaneous flaps. RESULTS: The colour and texture match of the reconstructed nose and lip is good. He could open his mouth wide enough and close completely. CONCLUSIONS: Facial reconstruction after PF is very difficult, because the patient has extensive scarring around the defect and there is little intact facial tissue. However, we performed a facial reconstruction using local flaps as much as possible, and obtained good results.

New way to raise the V-Y advancement flap for reconstruction of the lower lip: bipedicled orbicularis oris musculocutaneous flap technique.

We describe a new way to raise the V-Y advancement flap, which is useful for reconstruction of the lower lip. Various other methods have been reported in the past, but it has been necessary to choose the most suitable method for each particular case. A V-Y advancement flap from the submandibular region is one of the useful techniques to reconstruct the lower lip, and it is suitable for a wide horizontal defect. However, the conventional V-Y flap is insufficiently mobile and the reconstructed vermilion is thin because of the limitation of the pedicle. In such a case, the reconstructed lip may sag or cause an embarrassing defect. We developed a new way to raise the flap to obviate these problems. We use the V-Y advancement flap from the inferior margin of the defect in a conventional way after excision of the tumour, and use a mucosal flap to reconstruct the vermilion border. The skin side of the V-Y flap is undermined, and the orbicularis oris muscles are preserved on both sides as pedicles. The flap is then raised as a bipedicled musculocutaneous flap, which has adequate movement. After the flap has been sutured, the superior margin of the flap is de-epithelialised, and used to create the volume of the vermilion border. Functionally and cosmetically good results were achieved.

Midkine as a factor to counteract the deposition of amyloid ß-peptide plaques: in vitro analysis and examination in knockout mice.

BACKGROUND: Midkine is a heparin-binding cytokine involved in cell survival and various inflammatory processes. Midkine accumulates in senile plaques of patients with Alzheimer's disease, while it counteracts the cytotoxic effects of amyloid ß-peptide and inhibits its oligomerization. The present study was conducted to understand the role of midkine upon plaque formation of amyloid ß-peptide. METHODS: A surface plasmon assay was performed to determine the affinity of midkine for amyloid ß-peptide. The deposition of amyloid ß-peptide was compared in the brain of wild-type and midkine-deficient mice. An effect of midkine to microglias was examined by cell migration assay. RESULTS: Midkine bound to amyloid ß-peptide with the affinity of 160 nM. The C-terminal half bound to the peptide more strongly than the N-terminal half, and heparin inhibited midkine from binding to the peptide. Pleiotrophin, which has about 50% sequence identity with midkine also bound to amyloid ß-peptide. The deposition of amyloid ß-peptide plaques in the cortex and hippocampus was more intense in 15-month-old midkine-deficient mice, compared to the corresponding wild-type mice. Midkine promoted migration of microglias in culture. CONCLUSIONS: These results are consistent with the view that midkine attenuates the deposition of amyloid ß-peptide plaques, and thus progression of Alzheimer's disease, by direct binding and also by promoting migration of microglias.

Estlander flap combined with an extended upper lip flap technique for large defects of lower lip with oral commissure.

Various methods of reconstructing lower lip partial defects have been reported, for example those using the upper lip such as the Abbe and Estlander flap techniques. However, when a large defect of the lower lip with oral commissure is presented, the choice of reconstruction method is often difficult. For such cases, the Estlander flap technique is often used, although displacement of the oral commissure is one of the remaining problems. In the case of large defects of the lower lip with oral commissure, we opted for a reconstruction method in which the entire upper lip was incised and extended, a portion of which was reflected as a traditional Estlander flap. Four cases were treated using this method, and in all cases there were no complications such as venous return disturbance, and the site healed well. Sensation returned within 3 months, and contraction of the lips appeared within 6 months. The symmetry of oral commissures was maintained and the appearance was almost cosmetically satisfactory. Our technique is especially useful for reconstructing defects affecting 1/3-2/3 of the lower lip including the oral commissure. This technique is cosmetically and functionally successful and the symmetry of the oral commissure is maintained.