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An extensive spinal epidural abscess is a devasting infection of the multiple-level epidural space. Emergent surgical decompression is required to remove the abscess and decompress the affected spinal cord. This study evaluated the efficacy of unilateral laminotomy for bilateral decompression (ULBD) in the treatment of extensive spinal epidural abscesses.Three patients with extensive spinal epidural abscesses (epidural abscess involving more than 5 vertebral levels) were treated with the ULBD technique between September 2019 and August 2020. An ultrasonic curette was used for over-the-top decompression. Surgical drainage of the epidural abscess was performed concurrently with sublaminar drilling on top of the dura sac by using cold saline to automatically maintain the effluent in the ultrasonic curettage device.The 3 patients were men, with a mean age of 65.7 years. Diabetes mellitus, fever, and paraplegia were reported in all 3 patients. Escherichia coli, Staphylococcus aureus, and Streptococcus intermedius were cultured separately. The mean operative time was 163 minutes, and the mean estimated blood loss was 160 mL. All patients fully recovered from neurologic deficits and returned to preinjury levels of functioning at the final follow-up.As a minimally invasive technique, ULBD is a safe and effective treatment for extensive spinal epidural abscesses in critically ill patients. Moreover, the use of an ultrasonic bone curette not only safely accelerates over-the-top decompression but also flushes the epidural abscess with copious amount of cold saline.

Atopic dermatitis (AD) is a chronic inflammatory and pruritic disease; it can be treated by inhibiting inflammation. Sarcodia suiae sp. is an edible, artificially cultivable red algae with multiple bioactivities. We assessed the anti-inflammatory activity of the ethyl acetate fraction of S. suiae sp. ethanol extract (PD1) on 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions. Results show that PD1 alleviated symptoms and significantly decreased clinical dermatitis score. PD1 inhibited serum immunoglobulin E expression and alleviated swelling in the spleen and subiliac lymph nodes. In skin tissues, PD1 alleviated aberrant hyperplasia, decreased epidermal thickness, and decreased the accumulation of mast cells. PD1 mediated the recovery of skin barrier-related proteins, such as claudin-1 and filaggrin. Our study demonstrated that PD1 has anti-inflammatory effects, alleviates AD symptoms, inhibits inflammatory responses in skin tissues, and restores barrier function in DNCB-induced AD mice. These findings reveal that S. suiae sp. extract provides an alternative protective option against AD.

Background. Oxidative stress has been implicated in the pathogenesis of many diseases, including Parkinson’s disease. Large protein aggregates may be produced after the breakdown of the proteostasis network due to overt oxidative stress. Meanwhile, brain volume loss and neuropsychiatric deficits are common comorbidities in Parkinson’s disease patients. In this study, we applied a mediation model to determine the potential influences of oxidative stress-related plasma abnormal protein aggregate levels on brain volume and neuropsychiatric consequences in Parkinson’s disease. Method. 31 patients with PD and 24 healthy controls participated in this study. The PD patients were further grouped according to the presentation of cognitive decline or not. All participants received complete examinations to determine plasma abnormal protein aggregates levels, brain volume, and neuropsychiatric performance. The results were collected and analyzed in a single-level three-variable mediation model. Results. Patients with PD cognitive decline exhibited higher plasma NfL levels, decreased regional brain volume, and poor neuropsychiatric subtest results compared with PD patients with normal cognition, with several correlations among these clinical presentations. The mediation model showed that the superior temporal gyrus completely mediated the effects of elevated plasma NfL levels due to the poor psychiatric performance of picture completion and digit span. Conclusion. This study provides insight into the effects of oxidative stress-related plasma abnormal protein aggregate levels on regional brain volume and neuropsychiatric consequences in Parkinson’s disease patients.

BACKGROUND Artificial intelligence (AI) for gastric cancer diagnosis has been discussed in recent years. The role of AI in early gastric cancer is more important than in advanced gastric cancer since early gastric cancer is not easily identified in clinical practice. However, to our knowledge, past syntheses appear to have limited focus on the populations with early gastric cancer. OBJECTIVE The purpose of this study is to evaluate the diagnostic accuracy of AI in the diagnosis of early gastric cancer from endoscopic images. METHODS We conducted a systematic review from database inception to June 2020 of all studies assessing the performance of AI in the endoscopic diagnosis of early gastric cancer. Studies not concerning early gastric cancer were excluded. The outcome of interest was the diagnostic accuracy (comprising sensitivity, specificity, and accuracy) of AI systems. Study quality was assessed on the basis of the revised Quality Assessment of Diagnostic Accuracy Studies. Meta-analysis was primarily based on a bivariate mixed-effects model. A summary receiver operating curve and a hierarchical summary receiver operating curve were constructed, and the area under the curve was computed. RESULTS We analyzed 12 retrospective case control studies (n=11,685) in which AI identified early gastric cancer from endoscopic images. The pooled sensitivity and specificity of AI for early gastric cancer diagnosis were 0.86 (95% CI 0.75-0.92) and 0.90 (95% CI 0.84-0.93), respectively. The area under the curve was 0.94. Sensitivity analysis of studies using support vector machines and narrow-band imaging demonstrated more consistent results. CONCLUSIONS For early gastric cancer, to our knowledge, this was the first synthesis study on the use of endoscopic images in AI in diagnosis. AI may support the diagnosis of early gastric cancer. However, the collocation of imaging techniques and optimal algorithms remain unclear. Competing models of AI for the diagnosis of early gastric cancer are worthy of future investigation. CLINICALTRIAL PROSPERO CRD42020193223; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=193223

Surgical post-operative adhesions can lead to serious clinical complications. Barrier agent is the broad usage for the prevention of post-operative adhesions. This study aimed to evaluate the reducing adhesion efficacy of non-animal hyaluronic acid (HA) hydrogel in pigs undergoing conventional laparotomy pelvic surgery. HA hydrogel was applied to eighteen female pigs who underwent conventional laparotomy. The adhesion degrees and histopathology were evaluated in bilateral uterine horns as well as peritoneal sidewall excision. In the present study, all animals survived and had no complications after the surgery. The histopathological observations were demonstrated that HA obviously improved laparotomy pelvic surgery-induced adhesion in peritoneal sidewall and uterine horn. The anastomotic healing score of injury + HA group was significantly lower than the injury alone group. We conclude HA hydrogel can attenuate the post-operative adhesions in porcine.

Osteoarthritis (OA) is the most common joint disorder and is classically defined as a progressively degenerative disease of articular cartilage. It manifests as joint pain and disability and currently has no comprehensive treatments. The primary purpose of the present study was to test the effects of probiotics, Streptococcus thermophilus (TCI633), on anterior cruciate ligament transection (ACLT)-induced experimental osteoarthritis (OA) in rats. In the current study, the experimental groups were given TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) and glucosamine sulfate (250 mg/kg) between week 8 and 20 following ACLT. The results showed that oral administration of TCI633 and glucosamine had significant therapeutic effects on pain behaviors and knee swelling. Dose-dependent effects of TCI633 were also observed in ACLT-treated rats. Histopathological analysis demonstrated that ACLT+TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) improved the synovial inflammation and cartilage damage of ACLT rats. Histology evaluation using the Osteoarthritis Research Society International system and synovial inflammatory score analysis showed the dose-dependent inhibition of TCI633 on synovial inflammation and cartilage damage. Immunohistochemical staining and TUNEL apoptosis staining showed that TCI633 could effectively increase the expression of type II collagen and reduce the amount of chondrocyte apoptosis in cartilage. Therefore, the present study demonstrated that oral intake of TCI633 could significantly suppressing pain behavior, reduce joint swelling and synovial tissue inflammation and increase type II collagen expression in cartilage. There was also a reduction in chondrocyte apoptosis and decreased progression of OA in ACLT-treated rats.

Objectives The aim of this study was to evaluate the relationship between cognitive impairment and brain perfusion using arterial spin labelling (ASL) in end-stage renal disease (ESRD) patients undergoing PD. Methods ESRD patients undergoing PD were recruited. Laboratory screening, neuropsychological tests and ASL magnetic resonance imaging (MRI) were conducted prior to and after 6 months of PD. Age- and sex-matched normal subjects without ESRD served as the control group. Comparisons of regional CBF between ESRD patients before or after undergoing PD and normal controls were performed. Correlations between biochemical, neuropsychological and CBF data were also conducted to evaluate the relationships. Results ESRD patients showed poor performance in many of the neuropsychological tests; PD improved cognition in some domains. Pre-PD patients had higher mean CBF than post-PD patients and normal controls, but no significant difference was found between the normal controls and post-PD patients. Negative correlations were observed pre-PD (regional CBF in left hippocampus vs. perseverative responses, r = -0.662, p = 0.014), post-PD (mean CBF vs. haemoglobin level, r = -0.766, p = 0.002), and before and after PD (change in CBF in the left putamen vs. change in haematocrit percentage, r = -0.808, p = 0.001). Conclusion Before PD, ESRD patients had increased cerebral perfusion that was related to poorer executive function, especially in the left hippocampus. Post-PD patients performed better in some cognitive test domains than pre-PD patients. The degree of anaemia, i.e., haemoglobin level or haematocrit percentage, might predict cognitive impairment in PD patients. Key Points • In this study, ESRD patients before PD had cerebral hyperperfusion that was related to poorer executive function. • Post-PD patients performed better in some cognitive test domains than pre-PD patients did. • The degree of anaemia might predict cognitive impairment in PD patients. Electronic supplementary material The online version of this article (10.1007/s00330-018-5675-9) contains supplementary material, which is available to authorized users.

STUDY OBJECTIVES: Autonomic impairment and white matter (WM) alterations have been noted as effects of obstructive sleep apnea (OSA). This study sought to evaluate the change of WM integrity in patients with OSA using diffusion tensor imaging (DTI) and to determine its relationship with autonomic impairment. METHODS: A total of 30 patients with moderate and severe OSA and 19 healthy volunteers were recruited. A cardiovascular autonomic survey was performed and the baroreflex sensitivity (BRS) for each participant was derived from changes in heart rate and blood pressure during the early part of phase II of the Valsalva maneuver. DTI-related indices were derived from DTI. The fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were compared using voxel-based statistics to determine differences between the patients with OSA and the healthy controls. The correlations among DTI indices, clinical severity, and autonomic parameters were investigated. RESULTS: The BRS values were significantly worse in the OSA group than in the control patients. An exploratory group-wise comparison between the two groups revealed that the patients with OSA exhibited low FA, increased MD, AD, and RD in several brain locations. The declined DTI indices in autonomic-related areas were significantly correlated with increased clinical disease severity and baroreflex impairment. CONCLUSIONS: OSA alters WM integrity in the cingulum and temporal lobe, and this impairment might play some role in autonomic dysfunction. The possible interaction between autonomic dysfunction and central nervous system microstructural alterations may represent variant hypoxic patterns, sympathetic activation, and their consequent processes in OSA. CITATION: Chen H-L, Huang C-C, Lin H-C, et al. White matter alteration and autonomic impairment in obstructive sleep apnea. J Clin Sleep Med. 2020;16(2):293–302.

Background: Sarcopenia is critically associated with morbidity and mortality in the progression of Parkinson&rsquo, s disease (PD). However, analyses of clinical severity and brain changes, such as white matter (WM) alterations in PD patients with sarcopenia are limited. Further understanding of the factors associated with sarcopenia may provide a focused screen and potential for early intervention in PD patients. Methods: 52 PD patients and 19 healthy participants accepted dual-energy X-ray absorptiometry to measure the body composition. Using diffusion tensor imaging, the difference of WM integrity was measured between PD patients with sarcopenia (PDSa) and without sarcopenia (PDNSa). Multivariate analysis was performed to explore the relationships between clinical factors, WM integrity, and sarcopenia in PD patients. Results: 21 PD patients (40.4%) had sarcopenia. PDSa had a higher Unified Parkinson&rsquo, s Disease Rating Scale (UPDRS III) score, lower body mass index (BMI) and lower fat weight compared with the PDNSa. Additionally, PDSa patients exhibited lower fractional anisotropy accompanied by higher radial diffusivity and/or higher mean diffusivity in the fronto-striato-thalamic circuits, including bilateral cingulum, left superior longitudinal fasciculus, left genu of corpus callosum, and right anterior thalamic radiation, which participate in the executive function. In addition, decreased muscle mass was associated with worse WM integrity in these regions. Multiple linear regression analysis revealed that WM integrity in the left cingulum, right anterior thalamic radiation, together with gender (male) significantly predicted muscle mass in PD patients. Conclusions: WM alterations in the executive network, such as the fronto-striato-thalamic circuits, may indicate a risk factor for ongoing sarcopenia in PD patients. The effectiveness of using executive function to serve as a prodromal marker of sarcopenia in PD patients should be evaluated in future studies.

Osteoarthritis (OA) is the most common joint disorder and is classically defined as a progressively degenerative disease of articular cartilage. It manifests as joint pain and disability and currently has no comprehensive treatments. The primary purpose of the present study was to test the effects of probiotics, Streptococcus thermophilus (TCI633), on anterior cruciate ligament transection (ACLT)-induced experimental osteoarthritis (OA) in rats. In the current study, the experimental groups were given TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) and glucosamine sulfate (250 mg/kg) between week 8 and 20 following ACLT. The results showed that oral administration of TCI633 and glucosamine had significant therapeutic effects on pain behaviors and knee swelling. Dose-dependent effects of TCI633 were also observed in ACLT-treated rats. Histopathological analysis demonstrated that ACLT+TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) improved the synovial inflammation and cartilage damage of ACLT rats. Histology evaluation using the Osteoarthritis Research Society International system and synovial inflammatory score analysis showed the dose-dependent inhibition of TCI633 on synovial inflammation and cartilage damage. Immunohistochemical staining and TUNEL apoptosis staining showed that TCI633 could effectively increase the expression of type II collagen and reduce the amount of chondrocyte apoptosis in cartilage. Therefore, the present study demonstrated that oral intake of TCI633 could significantly suppressing pain behavior, reduce joint swelling and synovial tissue inflammation and increase type II collagen expression in cartilage. There was also a reduction in chondrocyte apoptosis and decreased progression of OA in ACLT-treated rats.

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.

Gingival recession (GR) potentially leads to the exposure of tooth root to the oral cavity microenvironment and increases susceptibility to dental caries, dentin hypersensitivity, and other dental diseases. Even though many etiological factors were reported, the specific mechanism of GR is yet to be elucidated. Given the species richness concerning marine biodiversity, it could be a treasure trove for drug discovery. In this study, we demonstrate the effects of a marine compound, (+)-rhodoptilometrin from crinoid, on gingival cell migration, wound healing, and oxidative phosphorylation (OXPHOS). Experimental results showed that (+)-rhodoptilometrin can significantly increase wound healing, migration, and proliferation of human gingival fibroblast cells, and it does not have effects on oral mucosa fibroblast cells. In addition, (+)-rhodoptilometrin increases the gene and protein expression levels of focal adhesion kinase (FAK), fibronectin, and type I collagen, changes the intracellular distribution of FAK and F-actin, and increases OXPHOS and the expression levels of complexes I~V in the mitochondria. Based on our results, we believe that (+)-rhodoptilometrin might increase FAK expression and promote mitochondrial function to affect cell migration and promote gingival regeneration. Therefore, (+)-rhodoptilometrin may be a promising therapeutic agent for GR.

Background and Aims: In order to evaluate the nephropathy with microproteinuria in T2DM in usual clinical care and ensuing development of personalized medicine. Materials and Methods: From Jan. 20to Dec. 2015, 14711 diabetes beneficiaries were randomly and cumulatively recruited in DCMP 2001 via outpatient clinic visit. Accordingly, the bi-annual urine and albumin creatinine ratio (ACR) examinations were routinely performed in patients enrolled. Nephropathy with microproteinuria was defined that the ACR was ≧30. From this studied cohort, there were 222 cases without taking any antidiabetes medication except lifestyle intervention as Group I whereas, 14489 cases with diabetes drugs including insulin used classified as Group II and III. Matching with age, sex, duration of diabetes and A1c levels and with 1: 4 ratio of case number, there were 60 cases with A1c (%) (Mean± SD) 6.72± 0.96 in Group I, 240 cases in Group II with A1c 7.01± 0.85 and Group III with A1c 8.19± 1.13 respectively in last 10 years. Data analysis was performed by using ANOVA and log-rank test for the occurrence of diabetes nephropathy with microproteinuria. Results: The baseline data among these 3 well-matched Groups were shown. There were no statistically significant difference of all metabolic measures among 3 Groups except FBG, A1c and serum TG that were significantly higher in Group III. The accumulating probability of diabetes nephropathy with microproteinuria amid these 3 Groups were totally identical and no statistically significant difference identified in 10-year time interval. Conclusions: The results clearly indicated that the risk factors rather than antidiabetes medications of diabetes nephropathy, duration of disease and even long-term glycemic control would be considered in this T2DM population cohort. Disclosure M.M.T. Fuh: None. P. Chen: None.

Purpose To evaluate the correlation between microstructural damage in the corpus callosum (CC) and the cognitive performance of patients with or without delayed encephalopathy (DE) after carbon monoxide (CO) intoxication in the chronic stage. Methods Diffusion tensor imaging (DTI) was performed more than 6 months after CO intoxication for 10 patients with DE and 10 patients without DE recruited from out-patient clinics, as well as for 15 normal controls (NCs). Using a probabilistic tractography method to parcel the CC based on fiber projections to cortical connectivity patterns, the DTI indices were calculated in the CC subregions and further correlated with cognitive performance. Results The DE group exhibited significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) values in the prefrontal, premotor, primary motor, primary sensory, parietal, and occipital CC subregions than did the NCs. The DE group also exhibited significantly lower FA values in the prefrontal and premotor subregions than did the non-DE group. Lower FA and higher RD values in the CC subregions were associated with poorer scores on the symbol search test. Conclusions CO intoxication may cause lower FA and higher RD in the CC subregions, with subsequent cognitive impairment. This finding suggests that selective CC damage after CO intoxication is more profound in patients with DE.

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.

In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue.

STUDY OBJECTIVES To evaluate white matter integrity in patients with obstructive sleep apnea (OSA) using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. DESIGN Cross-sectional study. SETTING One tertiary medical center research institute. PATIENTS OR PARTICIPANTS Twenty patients with severe OSA (apnea-hypopnea index [AHI] > 30, 18 men and 2 women) and 14 healthy volunteers (AHI < 5, 11 men and 3 women). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Patients with severe OSA and healthy volunteers underwent polysomnography to determine the severity of sleep apnea, and DTI scanning to determine fiber integrity. Early or late phase changes in leukocyte apoptosis and its subsets were determined by flow cytometry. DTI-related indices (including fractional anisotropy [FA], axial diffusivity [AD], radial diffusivity [RD], and mean diffusivity [MD]) were derived from DTI. The FA maps were compared using voxel-based statistics to determine differences between the severe OSA and control groups. The differences in DTI indices, clinical severity, and leukocyte apoptosis were correlated after adjusting for age, sex, body mass index, and systolic blood pressure. Exploratory group-wise comparison between the two groups revealed that patients with OSA exhibited low FA accomplished by high RD in several brain locations, without any differences in AD and MD. The FA values were negatively correlated with clinical disease severity and leukocyte early apoptosis. CONCLUSIONS Obstructive sleep apnea impairs white matter integrity in vulnerable regions, and this impairment is associated with increased disease severity. The possible interactions between systemic inflammation and central nervous system microstructural damage may represent variant hypoxic patterns and their consequent processes in OSA.

Research so far has only shown that edible red macroalgae, Sarcodia ceylanica has the ability to eliminate free radicals and anti-diabetic, anti-bacterial properties. This study was conducted both in vitro and in vivo on the ethyl acetate extract (PD1) of farmed red macroalgae in order to explore its anti-inflammatory properties. In order to study the in vitro anti-inflammatory effects of PD1, we used lipopolysaccharide (LPS) to induce inflammatory responses in murine macrophages. For evaluating the potential in vivo anti-inflammatory and antinociceptive effects of PD1, we used carrageenan-induced rat paw edema to produce inflammatory pain. The in vitro results indicated that PD1 inhibited the LPS-induced pro-inflammatory protein, inducible nitric oxide synthase (iNOS) in macrophages. Oral PD1 can reduce carrageenan-induced paw edema and inflammatory nociception. PD1 can significantly inhibit carrageenan-induced leukocyte infiltration, as well as the protein expression of inflammatory mediators (iNOS, interleukin-1β, and myeloperoxidase) in inflammatory tissue. The above results indicated that PD1 has great potential to be turned into a functional food or used in the development of new anti-inflammatory and antinociceptive agents. The results from this study are expected to help scientists in the continued development of Sarcodia ceylanica for other biomedical applications.

Background Systemic inflammation and white matter (WM) alterations have been noted as effects of Parkinson’s disease (PD). This study sought to evaluate WM integrity in PD patients using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. Methods Sixty-six patients with PD (23 men and 43 women) and 67 healthy volunteers (29 men and 38 women) underwent blood sampling to quantify inflammatory markers and DTI scans to determine fiber integrity. The inflammatory markers included leukocyte apoptosis, as well as cellular and serum adhesion molecules, in each peripheral blood sample. DTI-related indices [including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] were derived from DTI scans. The resulting FA maps were compared using voxel-based statistics to determine differences between the PD and control groups. The differences in the DTI indices, clinical severity, and inflammatory markers were correlated. Results Exploratory group-wise comparison between the two groups revealed that the PD patients exhibited extensive DTI index differences. Low FA accompanied by high RD and MD, without significant differences in AD, suggesting a demyelination process, were found in the parietal, occipital, cerebellar, and insular WM of the PD patients. The declined DTI indices were significantly correlated with increased clinical disease severity, adhesion molecules, and leukocyte apoptosis. Conclusions Patients with PD experience WM integrity damage in vulnerable regions, and these impairments are associated with increased disease severity and systemic inflammation. The possible interactions among them may represent variant neuronal injuries and their consequent processes in PD. Electronic supplementary material The online version of this article (doi:10.1186/s12868-017-0367-y) contains supplementary material, which is available to authorized users.

Parkinson's disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel-wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra-striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato-cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato-cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices. Hum Brain Mapp 36:1567–1584, 2015. © 2014 Wiley Periodicals, Inc.

Two new steroids, dendronesterones D (1) and E (2), featuring with 1,4-dienone moiety, along with three known steroids, methyl 3-oxochola-4,22-diene-24-oate (3), 5&alpha, 8&alpha, epidioxy-24(S)- methylcholesta-6,22-dien-3&beta, ol (4), and 5&alpha, epidioxy-24(S)-methylcholesta-6,9(11),22-trien-3&beta, ol (5), were isolated from an octocoral Dendronephthya sp. The structures of steroids 1 and 2 were elucidated by using spectroscopic methods and steroid 1 was found to exhibit significant in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein.

The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.

Systemic inflammation and alterations to regional cerebral blood flow (CBF) have been reported previously in obstructive sleep apnea (OSA). This study utilized arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI) to evaluate CBF in OSA patients and determine its relationship with systemic inflammation. Twenty male patients with moderate and severe OSA [apnea-hypopnea index (AHI) >15] and 16 healthy male volunteers (AHI

Additional file 1: Supplementary methods of DTI data preprocessing and analysis.

Background. Cardiovascular autonomic dysfunction is well known in Parkinson’s disease (PD) presentation and it produces hypoperfusion of vital organs. The association between cardiovascular autonomic dysfunction and oxidative stress was examined in previous animal models. Oxidative stress and neuroinflammation were thought to have roles in PD pathogenesis. Owing to the relative low intrinsic antioxidative properties, brain white matter (WM) is vulnerable to the oxidative stress. This study is conducted to examine possible relationships by using a hypothesis-driven mediation model. Methods. Twenty-nine patients with PD and 26 healthy controls participated in this study, with complete examinations of cardiac autonomic parameters, plasma DNA level, and WM integrity. A single-level three-variable mediation model was used to investigate the possible relationships. Results. The elevated serum oxidative stress biomarkers include plasma nuclear DNA and mitochondrial DNA, and poorer cardiac autonomic parameters and multiple regional microstructural WM changes are demonstrated. Further mediation analysis shows that plasma nuclear DNA served as the mediators between poorer baroreflex sensitivity and mean diffusivity changes in cingulum. Conclusions. These results provide a possible pathophysiology for how the poor baroreflex sensitivity and higher oxidative stress adversely impacted the WM integrity. This model could provide us with a piece of the puzzle of the entire PD pathogenesis.

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

Supplemental Digital Content is available in the text, Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

Additional file 1. The procedure for the cross-sectional voxel-based morphometry pipeline.

A robust and convenient research strategy integrating state-of-the-art analytical techniques is needed to efficiently discover novel compounds from marine microbial resources. In this study, we identified a series of amino-polyketide derivatives, vitroprocines A-J, from the marine bacterium Vibrio sp. QWI-06 by an integrated approach using imaging mass spectroscopy and molecular networking, as well as conventional bioactivity-guided fractionation and isolation. The structure-activity relationship of vitroprocines against Acinetobacter baumannii is proposed. In addition, feeding experiments with 13C-labeled precursors indicated that a pyridoxal 5′-phosphate-dependent mechanism is involved in the biosynthesis of vitroprocines. Elucidation of amino-polyketide derivatives from a species of marine bacteria for the first time demonstrates the potential of this integrated metabolomics approach to uncover marine bacterial biodiversity.

Background Chronic neuropsychological sequelae may occur in patients with tuberculous meningitis (TBM). The impact of structural abnormalities on the clinical performance of patients with TBM is unknown. This study applied the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) voxel-based morphometry (VBM) to determine if gray matter deficits in TBM are associated with acute presentations and chronic cognitive impairment. Methods Seventeen patients with TBM who discontinued their anti-TB therapy for more than six months, and 17 age-, sex-, and education-matched healthy subjects were enrolled. Differences in gray matter volume (GMV) between patients and healthy controls were investigated using DARTEL-VBM to determine structural abnormalities. Disease severity during the acute stage was scored by clinical profiles and conventional imaging findings. Correlations among chronic structural deficits, cognitive impairment, and initial disease severity were assessed. Results The patients with TBM had worse neuropsychological subtest performances than the healthy controls. Compared to the controls, the patients showed smaller GMVs in the right thalamus, right caudate nucleus, right superior and middle temporal gyrus, right precuneus, and left putamen (p

Parkinson's disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel‐wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra‐striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato‐cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato‐cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices. Hum Brain Mapp 36:1567–1584, 2015. © 2014 Wiley Periodicals, Inc.

Seven novel withanolides, sinubrasolides A-G (1-7), have been isolated from the cultured soft coral Sinularia brassica. The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of 1 was established by X-ray crystallographic analysis. The cytotoxicities of compounds 1-7 against a limited panel of cancer cell lines also were determined.

Background Patients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood. Methods Magnetic resonance imaging and neuropsychological tests were conducted on 11 CO patients with DE, 11 patients without DE, and 15 age-, sex-, and education-matched healthy subjects. Differences in gray matter volume (GMV) between the subgroups were assessed and further correlated with diminished cognitive functioning. Results As a group, the patients had lower regional GMV compared to controls in the following regions: basal ganglia, left claustrum, right amygdala, left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated with decreased perceptual organization and processing speed function. Those CO patients characterized by DE patients had a lower GMV in the left anterior cingulate and right amygdala, as well as lower levels of cognitive function, than the non-DE patients. Conclusions Patients with CO intoxication in the chronic stage showed a worse cognitive and morphologic outcome, especially those with DE. This study provides additional evidence of gray matter structural abnormalities in the pathophysiology of DE in chronic CO intoxicated patients.

Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.