Brain metabolic correlates of fatigue in Parkinson's disease: a PET study.

PURPOSE: The neural bases of fatigue in Parkinson's disease (PD) remain uncertain. We aimed to assess the brain metabolic correlates of fatigue in patients with PD. PATIENTS AND METHODS: Twenty-seven PD patients without clinically relevant depression (17-item Hamilton Depression Rating Scale (HAMD) score ≥ 14), apathy (Apathy Scale (AS) score ≥ 14) and excessive daytime somnolence (Epworth Sleepiness Scale (ESS) score ≥ 10) were evaluated with Fatigue Severity Scale (FSS). Each patient had an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale motor part. Levodopa equivalent daily dose for each patient was also calculated. The PET images were analyzed using statistical parametric mapping software. We introduced the age, educational level, HAMD scores, AS scores and ESS scores as covariates. RESULTS: High FSS scores were associated with brain hypermetabolism in areas including the right middle temporal gyrus (Brodmann area (BA) 37) and left middle occipital gyrus (BA 19). Increased FSS scores correlated with hypometabolism in regions such as the right precuneus (BA 23), left inferior frontal gyrus (BA 45) and left superior frontal gyrus (orbital part, BA 11). CONCLUSION: This study demonstrates that brain areas including frontal, temporal and parietal regions indicative of emotion, motivation and cognitive functions are involved in fatigue in PD patients.

Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson's disease.

The aim of our study is to examine the plasma levels of the four kinds of neurodegenerative proteins in plasma: α-syn, T-tau, P-tau181, and Aß-42 in Parkinson's disease (PD) and to evaluate the relationship between their plasma levels and PD motor subtypes. 84 patients with PD were enrolled in our study, and finally, 73 of them were classified into the tremor-dominant subtype (TD) and the postural instability gait difficulty subtype (PIGD). Their motor performance was evaluated by a series of clinical assessments: Freezing of Gait Questionnaire (FOGQ), Timed Up and Go (TUGs), Tinetti balance, and Tinetti gait. Plasma levels of these proteins were measured by enzyme-linked immunosorbent assay (ELISA). The plasma level of α-syn was significantly higher in PD patients when compared to controls (p = 0.004), and significantly higher in the PIGD group when compared to the TD group (p = 0.03). While the plasma level of Aß-42 was significantly lower in PD patients than in controls (p = 0.002), and significantly lower in the PIGD group than in the TD group (p = 0.05). In PD patients, the plasma level of α-syn (r = -0.355, p < 0.001) was significantly related to the severity of Tenitti Gait score, even after performing multiple linear regression (p = 0.002). While the plasma level of Aß-42 (r = -0.261, p < 0.05) was significantly associated with the severity of PIGD score and remained correlate when performed multiple linear regression (p = 0.005). The patients with PIGD subtype are characterized with a lower level of plasma Aß-42 and a higher plasma level of α-syn, which may be used as biomarkers for diagnosis and progression of the subtypes of PD.

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson's disease.

Fatigue is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.

Regional homogeneity alterations differentiate between tremor dominant and postural instability gait difficulty subtypes of Parkinson's disease.

Parkinson's disease (PD) can be classified into the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype, which present with different clinical courses and prognoses. However, the symptom-specific intrinsic neural mechanisms underlying the subtypes of PD still remain elusive. In the current study, we utilized resting-state fMRI (rs-fMRI) combined with the regional homogeneity (ReHo) method to investigate the modulations of neural activity in 13 patients with predominantly PIGD (p-PIGD) and 15 patients with predominantly TD (p-TD) in the resting state. Compared with healthy controls, the p-PIGD and the p-TD groups both displayed ReHo changes in the default mode network (DMN). By contrast, the p-TD group exhibited more ReHo alterations in the cerebellum involved in the cerebello-thalamo-cortical (CTC) loops, whilst the p-PIGD group in extensive cortical and sub-cortical areas, including the frontal, parietal, occipital, temporal, limbic lobes, basal ganglia and thalamus, which are involved in the striatal-thalamo-cortical (STC) loops. Direct comparison between the two groups showed significant ReHo alterations in the primary visual cortex. Our findings underscore the differential involvement of the STC and CTC circuits underlying the two subtypes of PD. Moreover, relatively widespread neural activity abnormality, especially in the motor-related regions as well as the visual network, is apparently a characteristic feature of PIGD symptoms. This study could shed light on the underlying pathophysiology and clinical heterogeneity of PD presentation.

Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment.

PURPOSE: This study aimed to evaluate the level of taurine in plasma, and its association with the severity of motor and non-motor symptoms (NMS) and chronic levodopa treatment in Parkinson's disease (PD). PATIENTS AND METHODS: Plasma taurine level was measured in treated PD (tPD), untreated PD (ntPD) and control groups. Motor symptoms and NMS were assessed using the Unified Parkinson's Disease Rating Scale, the short form of the McGill Pain Questionnaire, the Hamilton Depression Scale, the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms and the Pittsburgh Sleep Quality Index. Longtime exposure to levodopa was indicated by its approximate cumulative dosage. RESULTS: The plasma taurine levels of PD patients were decreased when compared with controls and negatively associated with motor severity but not NMS. Moreover, tPD patients exhibited lower levels of plasma taurine than ntPD patients. Interestingly, plasma taurine levels negatively correlated with cumulative levodopa dosage in tPD. After controlling for potential confounders, the association between taurine and levodopa remained significant. CONCLUSION: Our study supports that taurine may play important roles in the pathophysiology of PD and the disturbances caused by chronic levodopa administration.

Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients.

PURPOSE: This study aimed to explore plasma antioxidant status in de novo Chinese Parkinson's disease (PD) patients and investigate its relationship with specific motor features of PD. PATIENTS AND METHODS: Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinson's disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearman's coefficient. RESULTS: Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. CONCLUSION: Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.

The association between clinically relevant anxiety and other non-motor symptoms in Parkinson's disease.

Anxiety disorders in patients with Parkinson's disease (PD) are often missed due to an overlap with other non-motor symptoms. The relationships between anxiety and other non-motor symptoms in PD still remain unclear. We used the Hamilton anxiety rating scale and the Non-motor Symptoms Questionnaire to measure anxiety and the complex range of non-motor symptoms in 99 PD patients. The relationships between anxiety and other PD-related non-motor symptoms were examined through regression analyses. 25 % of PD patients were diagnosed with clinically relevant anxiety. Non-motor symptoms were more prominent in patients with anxiety. Depression, urinary disorders, and sleep disruption were the factors most likely to influence anxiety in PD. Our findings have revealed a strong interplay between anxiety and other non-motor symptoms of PD and have highlighted the need for a holistic approach towards the clinical treatment of this disabling condition.

Identify the Clinicopathological Characteristics of Lung Carcinoma Patients Being False Negative in Folate Receptor Based Circulating Tumor Cell Detection.

In lung cancer diagnosis, folate receptor (FR)-based circulating tumor cell (CTC) has shown its ability to distinguish malignancy from benign disease to some extent. However, there are still some patients that cannot be identified by FR-based CTC detection. And studies comparing the characteristics between true positive (TP) and false negative (FN) patients are few. Thus, the study comprehensively analyzes the clinicopathological characteristics of FN and TP patients in the current study. According to inclusion and exclusion criteria, 3420 patients are enrolled. Combining the pathological diagnosis with CTC results, patients are divided into FN and TP groups, and clinicopathological characteristics are compared between two groups. Compared with TP patients, FN patients have smaller tumor, early T stage, early pathological stage, and without lymph node metastasis. Epidermal growth factor receptor (EGFR) mutation status is different between FN and TP group. And this result is also demonstrated in lung adenocarcinoma subgroup but not in lung squamous cell carcinoma subgroup. Tumor size, T stage, pathological stage, lymph node metastasis, and EGFR mutation status may influence the accuracy of FR-based CTC detection in lung cancer. However, further prospective studies are needed to confirm the findings.

Efficacy evaluation of surgery combined with chemotherapy for stage IIIA small cell lung cancer patients: a retrospective analysis.

Background: The efficacy of surgery in combination of chemotherapy for stage IIIA small cell lung cancer (IIIA-SCLC) is controversial. The aim of the present study was to analyze the efficacy of surgery combined with chemotherapy, especially in the setting of neoadjuvant chemotherapy (NAC) followed by surgery for IIIA-SCLC. Methods: Between 2004 and 2015, we reviewed 2,199 chemotherapy-treated stage IIIA (N1/2) SCLC cases in the Surveillance, Epidemiology, and End Results (SEER) database, and 32 NAC + intentional radical resection-treated, centrally-located IIIA-SCLC cases at Shanghai Pulmonary Hospital (SPH). Outcomes were compared between surgically and non-surgically treated patients from the SEER database after propensity score matching (PSM), and comparing lobectomy/bi-lobectomy and pneumonectomy patients from SPH. Prognostic factors were evaluated by Kaplan-Meier method and the Cox proportional hazards regression model. Results: There was significantly higher overall survival (OS) in surgically treated IIIA-SCLC patients (OS, 44.8 vs. 21.2 months, P=0.048), and similar efficacy was observed between sub-lobectomy and lobectomy/bi-lobectomy patients (OS: 55.6 vs. 30.3 months, P=0.167) in SEER database. At SPH, significantly higher OS was associated with T1 stage (before NAC: T1 vs. T2-4, 48.7 vs. 32.2 months, P=0.025; after NAC: T1 vs. T2-4, 42.7 vs. 21.3 months, P=0.048). Female sex [hazard ratio (HR): 0.078, P=0.009], T1 stage (HR: 13.048, P=0.026), and pneumonectomy (HR: 0.095, P=0.009) were independent prognostic factors for IIIA-SCLC patients who received NAC + intentional radical resection. Conclusions: For stage IIIA SCLC patients, complete resection combined with chemotherapy might improve the prognosis than patients without surgery. Post-NAC lobectomy was not found to be superior to sub-lobectomy, while pneumonectomy was considered suitable for central-type IIIA-SCLC patients after NAC treatment.

Extended Sleeve Lobectomy is an Alternative for Centrally Located Lung Cancer With Superior Short- and Long-term Outcomes.

INTRODUCTION: Extended sleeve lobectomy (ESL) is a feasible alternative to pneumonectomy; however, the survival benefit is unclear, and preoperative selection of potential candidates for ESL remains a problem. MATIERALS AND METHODS: ESL was performed on selected candidates with double sleeve lobectomy for more than 1 lobe (eg, left upper lobe and S6 segment resection). Three-dimensional (3-D) reconstruction was routinely validated. Patients were candidates for ESL if the predicted distal stump length was > 6 mm and the pulmonary vein of the remaining segments was not invaded. RESULTS: Of the 1809 patients with centrally located lung cancer for surgical resection, 86 patients with tumors invading more than 1 lobe were enrolled in the study. After evaluation by 3-D reconstruction, 22 (95.7%) of 23 selected candidates underwent ESL, and 63 patients were deemed unsuitable for ESL and underwent pneumonectomy (43 cases) or thoracic exploration (20 cases). Surgical outcomes between the ESL and pneumonectomy groups were similar in terms of complications, blood loss and surgical duration, but the 6-minute walking distance was significantly improved in the ESL group (371 ± 111 m vs. 191 ± 55 m, respectively; P < .001). The mean forced expiratory volume in 1 second was 1.6 ± 0.3 L at the 1-year follow up examination in the ESL group. In the survival analysis, no difference was observed between the ESL and pneumonectomy groups in terms of 3-year overall survival (85% vs. 89%, respectively; P = .626) and 3-year disease-free survival (75% vs. 76%, respectively; P = .625). CONCLUSIONS: ESL is a feasible and superior surgical procedure in terms of its short-term and long-term outcomes, and we suggest 3-D reconstruction to identify candidates for ESL.

Lung cancers associated with cystic airspaces: CT features and pathologic correlation.

OBJECTIVE: Lung cancer associated with cystic airspaces (LCCA) is a rare entity. The diagnosis and treatment is often delayed due to lack of comprehension of this disease. We aimed to elucidate LCCA's clinicopathological characteristics and investigate imaging features correlated with pathological invasiveness. METHOD: The preoperative computed tomographic (CT) scans of 10,835 patients diagnosed with NSCLC between January 2015 and December 2016 were reviewed by two thoracic radiologists for association with a cystic airspace. A clinicopathological and radiological feature analysis was done. RESULT: A total number of 123 LCCA patients were identified and four morphologic patterns were recognized: I, thin-walled type (n = 23, 18.7%); II, thick-walled type (n = 34, 27.6%); III, a cystic airspace with a mural nodule (CWN) type (n = 43, 35.0%); and IV, mixed type (n = 23, 18.7%). A solid component in the cyst wall predicted histological invasiveness in all four types of LCCA. The proportion of moderately/poorly (M/P)-differentiated subtype in type III (85.0%) was higher than in other three patterns (which were 50.0%, 50.0%, and 69.6%, respectively). Multivariate analysis revealed that type III pattern (odds ratio [OR], 6.5; 95% confidence interval [CI], 1.1-36.4; P = 0.035), part-solid/solid component in wall (part-solid: OR, 27.2; 95% CI, 5.6-3131.6; P < 0.001; solid: OR 614.6; 95% CI, 36.4-10,368.6; P < 0.001), and irregular inner surface of cyst (OR 7.0; 95% CI 1.9-26.2; P = 0.004) were independent risk factors for the M/P-differentiated subtype. EGFR mutations were the predominant genetic alterations in each type of LCCAs, but no significant difference was found among them. CONCLUSIONS: In LCCA, morphological patterns and wall components were two important predictors for determining pathological invasiveness.

Decreased interhemispheric homotopic connectivity in Parkinson's disease patients with freezing of gait: A resting state fMRI study.

INTRODUCTION: Freezing of gait is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of freezing of gait in PD remain uncertain. Existing studies on PD patients with freezing of gait (PD-FOG+) have reported damage of the corpus callosum, the largest commissural bundle of the brain. Thus, in this study we explored homotopic connectivity to investigate FOG-related interehemispheric alterations METHODS: A total of 21 PD-FOG + patients, 33 PD patients without freezing of gait (PD-FOG-), and 24 matched healthy controls were recruited. All PD patients were evaluated via the FOG questionnaire (FOGQ) and all subjects had a resting state functional magnetic resonance imaging (rs-fMRI) scan. The pattern of the homotopic connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. RESULT: The PD-FOG + patients showed decreased VMHC values in the inferior parietal lobe (IPL) compared to both PD-FOG-patients and healthy controls. In PD-FOG + patients, the mean VMHC values in the IPL were negatively correlated with the FOGQ scores. Receiver operating characteristic curves analyses revealed that the VMHC in the IPL had discriminatory function distinguishing PD-FOG + patients from PD-FOG-patients or healthy controls. CONCLUSION: Decreased VMHC values of PD-FOG + patients relative to PD-FOG- and healthy controls in IPL maybe a unique feature for PD-FOG+ and it may have the ability to separate PD-FOG + patients from PD-FOG- and healthy controls.

Cerebral metabolic change in Parkinson's disease patients with anxiety: A FDG-PET study.

OBJECT: To detect the cerebral metabolic bases of Parkinson's disease (PD) patients with anxiety. METHODS: Totally 28 idiopathic PD patients without depression (17-item Hamilton Depression Rating Scale, HAMD score <14) were enrolled in our study. All subjects were classified into PD with anxiety (PD-A) (n=13) and PD without anxiety (PD-NA) (n=15) by cutoff score of 11 according to Hamilton Anxiety Rating Scale (HAMA). Besides, age- and gender- matched healthy controls (HCs) (n=15) were selected. A resting-state F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan was applied to estimate cerebral metabolic activity. All statistical analyses were performed using IBM SPSS Statistics V20.0.0 software, while statistical parametric mapping software (SPM) was used to analyze the FDG-PET images. RESULTS: PD-A showed decreased glucose metabolism in the bilateral orbitofrontal cortex (OFC, BA10 and BA11) when compared with PD-NA. Significant decrease of cerebral glucose metabolism in the bilateral OFC, bilateral supplementary motor area (SMA, BA6), bilateral dorsal anterior cingulate cortex (dACC, BA32), right dorsolateral prefrontal cortex (dlPFC, BA9), right ventrolateral prefrontal cortex (vlPFC, BA44), right putamen and left caudatum was detected in PD-A compared with HCs. There was significant reduced glucose metabolism of the bilateral SMA in PD-NA when compared with HCs (uncorrected p<0.005). CONCLUSION: The anxiety of PD was associated with the metabolic reductions of PFC and striatal areas. OFC, part of PFC, could be taken as a characteristic feature for anxiety in PD. This metabolic pattern suggested that deficits of prefrontostriatal pathways might affect anxiety mood in PD.

Abnormal Resting-State Neural Activity and Connectivity of Fatigue in Parkinson's Disease.

AIMS: Fatigue is a common burdensome problem in patients with Parkinson's disease (PD), but its pathophysiological mechanisms are poorly understood. This study aimed at investigating the neural substrates of fatigue in patients with PD. METHODS: A total of 17 PD patients with fatigue, 32 PD patients without fatigue, and 25 matched healthy controls were recruited. The 9-item fatigue severity scale (FSS) was used for fatigue screening and severity rating. Resting-state functional magnetic resonance imaging (RS-fMRI) data were obtained from all subjects. Amplitude of low-frequency fluctuations (ALFF) was used to measure regional brain activity, and functional connectivity (FC) was applied to investigate functional connectivity at a network level. RESULTS: PD-related fatigue was associated with ALFF changes in right middle frontal gyrus within the attention network and in left insula as well as right midcingulate cortex within the salience network. FC analysis revealed that above three regions showing ALFF differences had altered functional connectivity mainly in the temporal, parietal, and motor cortices. CONCLUSION: Our findings do reveal that abnormal regional brain activity within attention and salience network and altered FC of above abnormal regions are involved in neural mechanism of fatigue in patients with PD.

Uniportal video-assisted thoracic surgery-the experiences of Shanghai Pulmonary Hospital.

Uniportal video-assisted thoracic surgery (VATS) is getting recognized in thoracic surgery, especially in China. Although surgeons from some part of the world are still skeptic, those in China have witnessed its breathtaking growth, along with the development of the specialty of thoracic surgery. By introducing the history and experiences of one specialty hospital-Shanghai Pulmonary Hospital (SPH), we show the feasibility and safety of uniportal VATS, and illustrate the technical details of this procedure with the example of right middle lobectomy (RML).

Alterations of functional and structural connectivity of freezing of gait in Parkinson's disease.

This study assessed the patterns of functional and structural connectivity abnormalities in patients with Parkinson's disease with freezing of gait (PD FOG+) compared with those without freezing (PD FOG-) and healthy controls (HCs). Resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) scans were obtained from 14 PD FOG+, 16 PD FOG- and 16HCs. Between-group difference in pedunculopontine nucleus (PPN) functional connectivity (FC) was performed to assess FC dysfunction. Tract-based spatial statistics (TBSS) was applied to compare white matter (WM) impairment across the whole brain between groups. PD FOG+ patients exhibited abnormal PPN FC, compared with HCs and with PD FOG-, mainly in the corticopontine-cerebellar pathways (in the bilateral cerebellum and in the pons), as well as the visual temporal areas (in the right middle temporal gyrus and in the right inferior temporal gyrus). Moreover, PD FOG+ patients, showed more pronounced WM abnormalities, relative to controls, including the interhemispheric connections of corpus callosum, the cortico-cortical WM tracts of the cingulum, the superior longitudinal fasciculus and inferior fronto-occipital fasciculus, the corticofugal tract (cerebral peduncles, internal capsule, corona radiata), as well as tracts connecting the thalamus (thalamic radiation). This study suggests that FOG in PD is associated with abnormal PPN FC network, mainly affecting the corticopontine-cerebellar pathways as well as visual temporal areas involved in visual processing, and with diffuse WM deficits extending to motor, sensory and cognitive regions. Combining rs-fMRI and DTI method, our study should advance the understanding of neural mechanisms underlying FOG in PD.

The Neural Basis of Postural Instability Gait Disorder Subtype of Parkinson's Disease: A PET and fMRI Study.

AIMS: The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinson's disease. METHODS: With F-18 fluorodeoxyglucose PET (FDG-PET), brain glucose metabolism of patients with PIGD (n = 15) was compared with healthy controls (n = 17) and tremor-dominant (TD) patients (n = 15), and the correlation between metabolism and PIGD symptoms was also assessed. Within PIGD symptom-correlated hypometabolic areas, the relationship of functional connectivity (FC) with motor and cognitive symptoms was examined by using functional MRI. RESULTS: Compared with controls, patients with PIGD displayed a distributed pattern of brain hypometabolism including striatal, frontal, and parietal areas. Relative to the pattern of TD patients, the pattern of patients with PIGD had additional metabolic decreases in caudate and inferior parietal lobule (IPL, Brodmann area [BA] 40). In PIGD group, the metabolic reductions in IPL (BA 40), middle frontal gyrus (MFG, BA 9) and fusiform gyrus (FG, BA 20) were associated with severe PIGD symptoms. Regions showing such correlation were chosen for further seed-based FC analysis. Decreased FC within the prefrontal-parietal network (between the MFG and IPL) was associated with severe PIGD symptoms. CONCLUSION: The involvement of the caudate, FG, and prefrontal-parietal network may be associated with the prominent gait impairments of PIGD subtype. Our findings expand the pathophysiological knowledge of PIGD subtype and provide valuable information for potential neuromodulation therapies alleviating gait disorders.

Reduced plasma serotonin and 5-hydroxyindoleacetic acid levels in Parkinson's disease are associated with nonmotor symptoms.

BACKGROUND: Accumulating evidence suggests that serotonergic system may be implicated in the pathophysiology of Parkinson's disease (PD), and particularly in nonmotor symptoms such as depression, fatigue, sleep disorders, sensory and autonomic dysfunction. This study aimed to evaluate plasma levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in PD patients, and investigate their associations with nonmotor symptoms. METHODS: Eighty-two PD patients and sixty-four controls underwent a series of clinical assessments, including Hamilton Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Visual Analog Scale for Pain, and Scale for Outcomes in PD for Autonomic Symptoms. Plasma 5-HT and 5-HIAA levels were measured by HPLC-ECD. RESULTS: PD patients exhibited worse performance on nonmotor symptom scales (all P-values <0.001) and presented lower plasma levels of 5-HT (P < 0.001) and 5-HIAA (P < 0.001) than control individuals. Within the PD group, decreased concentrations of plasma 5-HT and 5-HIAA were correlated with more severe depression (r = -0.447, P < 0.001; r = -0.407, P < 0.001, respectively) and pain (r = -0.485, P < 0.001; r = -0.416, P < 0.001, respectively). After performing multiple linear regression, plasma 5-HT (P = 0.01) and 5-HIAA (P = 0.006) remained significantly associated with depression. CONCLUSIONS: Our results suggest that serotonergic dysfunction might exist in PD, and specifically correlated with depression and pain in PD. Plasma levels of 5-HT and 5-HIAA may be considered as peripheral markers for depression in PD.

Video-assisted thoracic surgery for bronchiectasis.

BACKGROUND: Bronchiectasis is one of the common diseases diagnosed in the world. No major improvement for the treatment approaches and limited efficacy promote a big challenge for management of this disease. Video-assisted thoracoscopic surgery (VATS) offers a new choice for the treatment of bronchiectasis. The purpose of this study was to present our experience of VATS for bronchiectasis and to compare this with thoracotomy in our institution. METHODS: We reviewed the medical records of patients who underwent VATS lobectomy and general lobectomy for bronchiectasis between January 2005 and December 2009. RESULTS: A total of 279 patients underwent thoracotomy, 52 patients underwent attempted VATS lobectomy. Fifty-two patients from 279 patients for thoracotomy were selected and compared with the VATS group. Pleural adhesion was observed in 15 patients (28.8%) in VATS. The VATS lobectomy was converted to open thoracotomy in 7 patients. There was no difference in the blood loss and median operative time between the two groups, but the patients with VATS had shorter length of stay in hospital (p=0.045), fewer complications (p=0.039) than those with thoracotomy. Forty-nine (94%) and 46 (88%) patients fully recovered after operation by VATS and thoracotomy, respectively. CONCLUSIONS: Video-assisted thoracoscopic lobectomy in localized bronchiectasis is a safe and more efficient procedure in selected patients with better recovery.

Induction of neutralizing antibody against human immunodeficiency virus type 1 (HIV-1) by immunization with gp41 membrane-proximal external region (MPER) fused with porcine endogenous retrovirus (PERV) p15E fragment.

The membrane-proximal external region (MPER) of HIV-1 gp41 is recognized by all three anti-HIV antibodies 2F5, 4E10 and Z13 that were directly derived from AIDS patients and have broader anti-HIV neutralizing activities. Thus, the MPER has been the focus of anti-HIV vaccine design and development. However, it has been unsuccessful to generate anti-HIV neutralizing antibodies targeting this region. One possible reason is that the MPER-containing immunogens have failed to maintain the correct conformation of the MPER present within the HIV-1 viral gp41 protein. The porcine endogenous retrovirus (PERV) p15E protein is structurally similar to HIV-1 gp41, and it was recently reported that the p15E fragment can be expressed in soluble form and was capable of inducing neutralizing antibodies against the epitope within the MPER of PERV p15E. In the present study, we attempted to use the p15E fragment as a carrier and fused the HIV-1 gp41 MPER with the p15E fragment. The vesicular stomatitis virus (VSV) recombinants expressing the fusion proteins (HIV-1 gp41 MPER-p15E) were prepared as primary immunogens, and the soluble fusion protein purified from a baculovirus expression system as booster immunogens. Our results showed that the antisera obtained from immunized rabbits specifically recognized the MPER determinant presented in the gp41 fragment. Importantly, we found that the antisera had neutralizing activities against HIV-1 viruses containing HIV-1 HXB2 and JRFL envelope glycoproteins. These results offer a new strategy for HIV-1 vaccine design and development targeting the gp41 MPER.