Prevention of recognition memory loss and moderation of mitochondrial dynamic tendency toward fusion by flavone derivatives in Aβ-injected rats: a comparison between two flavonoids with different polarity

Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4?-trimethoxyflavone (flavone 1) and 5,7,4?-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aβ-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protein-1 protein level, a known marker for mitochondrial fission, and elevation in protein level of mitochondrial fusion factors Mitofusins 1 and 2. In parallel with behavior results, flavone 1 was more effectual on mitochondrial dynamic moderating. The more neuroprotective effects of flavone 1 could be attributed to its methylated structure leading to crossing of the blood-brain barrier with ease and metabolic stability and bioactivity.     

An Improved Method of Assessing Esophageal Emptying Using the Timed Barium Study Following Surgical Myotomy for Achalasia

Introduction  The timed barium study (TBS) is used to assess esophageal emptying in patients with achalasia. Improvement in emptying correlates with outcome after endoscopic therapy, but the results of the TBS have been variable after myotomy. Our aim was to evaluate a new method for assessing improvement in emptying after myotomy. Methods  A TBS was performed before and 3–6 months after myotomy in 30 patients. Emptying was assessed by measuring the percent difference in area of the barium column on films obtained 1 and 5 min after ingesting 150 ml of barium. Initial esophageal clearance was also assessed by comparing the area of the barium column on 1-min images obtained before and after therapy. Both measures were compared to clinical outcome. Results  After myotomy, 21 patients (70%) had no symptoms, four (13%) had mild, and five (17%) had moderate/severe symptoms. Using the standard method, esophageal emptying before and after surgery were not significantly different (25% vs. 37%; p = 0.22) and did not correlate with clinical outcome. In contrast, initial esophageal clearance improved significantly (median 81%) and correlated with clinical outcome. Conclusion  Esophageal emptying measured by the standard method is not useful to assess outcome after myotomy. However, initial esophageal clearance correlates well with clinical outcome. Previous presentations: 49th SSAT Annual Meeting at Digestive Disease Week, San Diego, 2008 and 23rd Annual SSAT Residents and Fellows Research Conference, San Diego, 2008     

Antidepressant-like effect of magnetic resonance imaging-based stimulation in mice

INTRODUCTION: It has been reported that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) may show antidepressant effects. We examined whether the two routine diagnostic protocols of MRI [T1 and echo planar diffusion weighted imaging (EPI-DWI)], have antidepressant-like effects in an animal model of depression. METHODS: The effects of standard EPI-DWI and T1 MRI on immobility, swimming and climbing times in the modified forced swimming test (FST) in mice were examined. After exposure to the first session of modified forced swimming test, we randomly divided the mice into four groups. The first group (T1 MRI group, n=21) received a 15-minute stimulation of T1 sequence. The second group (EPI-DWI MRI group, n=21) received a 15-minute stimulation of EPI-DWI protocol. The third group (sham group, n=21) spent 15 min in a tunnel similar to the MRI gantry in terms of size, temperature and light intensity and received recorded sounds from a normal session of EPI-DWI with similar duration and intensity. The fourth group acted as controls (n=21).The second session of the modified FST was conducted twelve hours later. The mean of immobility, swimming and climbing times in this session were compared to the control group. RESULTS: T1 weighted and EPI-DWI MRI groups showed a reduction in immobility time compared to the control group (P value<0.002, P value<0.017 respectively). This effect is comparable to that seen in the FST after the administration of antidepressant agents. The climbing time in the group subjected to EPI-DWI MRI was longer than the control group (P value<0.035). Previous studies showed similar effects after the administration of antidepressant drugs affecting the catecholamine systems. The swimming time in the T1 MRI group was significantly longer than the control group (P value<0.037). Previous studies showed qualitatively similar effect to that of anti-depressant drugs affecting the serotoninergic systems. The swimming, climbing and immobility times in the sham and control groups showed no significant difference. CONCLUSIONS: Our findings raise the possibility that MRI-based stimulation may have antidepressant-like effects in mice. This is likely to be through different mechanisms in T1 weighted and EPI-DWI protocols. However the possible biological basis of this effect is not yet understood and we would advocate further studies of MRI-based stimulation effects on transmitters in the different organs in the body specially the brain.     

Fistulous withers and eosinophilia in a horse

Fistulous withers is a chronic inflammatory disease of horses in the supraspinous bursa and associated tissues. The referred horse had a fistulous tract in the withers area with presence of purulent material accumulation under the ligamentum nuchae. The radiographic examination of the lesion showed an osteomyelitis involved area. The hematological examination revealed eosinophilia. Long-term antibiotic therapy reduced the eosinophilic reaction to normal. It was assumed that osteomyelitis was the cause of eosinophilia in this horse.     

Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia

Imatinib has revolutionized the treatment of Bcr-Abl1(+) chronic myeloid leukemia (CML), but, in most patients, some leukemia cells persist despite continued therapy, while others become resistant. Here, we report that PlGF levels are elevated in CML and that PlGF produced by bone marrow stromal cells (BMSCs) aggravates disease severity. CML cells foster a soil for their own growth by inducing BMSCs to upregulate PlGF, which not only stimulates BM angiogenesis, but also promotes CML proliferation and metabolism, in part independently of Bcr-Abl1 signaling. Anti-PlGF treatment prolongs survival of imatinib-sensitive and -resistant CML mice and adds to the anti-CML activity of imatinib. These results may warrant further investigation of the therapeutic potential of PlGF inhibition for (imatinib-resistant) CML.     

Distinct functions of antigen-specific CD4 T cells during murine Mycobacterium tuberculosis infection

The immune response elicited after Mycobacterium tuberculosis (Mtb) infection is critically dependent on CD4 T cells during both acute and chronic infection. How CD4 T-cell responses are maintained throughout infection is not well understood, and evidence from other infection models has suggested that, under conditions of chronic antigen stimulation, T cells can undergo replicative exhaustion. These findings led us to determine whether subpopulations of CD4 T cells existed that displayed markers of terminal differentiation or exhaustion during murine Mtb infection. Analysis of antigen-specific effector CD4 T cells revealed that programmed death-1 (PD-1) and the killer cell lectin-like receptor G1 (KLRG1) delineated subpopulations of T cells. PD-1-expressing CD4 T cells were highly proliferative, whereas KLRG1 cells exhibited a short lifespan and secreted the cytokines IFNγ and TNFα. Adoptive transfer studies demonstrated that proliferating PD-1-positive CD4 T cells differentiated into cytokine-secreting KLRG1-positive T cells, but not vice versa. Thus, proliferating PD-1-positive cells are not exhausted, but appear to be central to maintaining antigen-specific effector T cells during chronic Mtb infection. Our findings suggest that antigen-specific T-cell responses are maintained during chronic mycobacterial infection through the continual production of terminal effector cells from a proliferating precursor population.     

Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim

BACKGROUND: There is a misconception that elderly cancer patients cannot tolerate standard doses of chemotherapy because of the frequency and severity of myelosuppressive complications. The reactive use of colony-stimulating factors (i.e., in response to severe neutropenia) commonly observed in this setting contributes to the frequency and severity of these complications. This study evaluated the incidence of febrile neutropenia and related events in elderly cancer patients receiving pegfilgrastim beginning with cycle 1 (proactive) in comparison with pegfilgrastim initiated after cycle 1 at the physician's discretion (reactive). METHODS: Patients (> or = 65 years of age) with either solid tumors or non-Hodgkin's lymphoma (NHL) were randomly assigned to receive pegfilgrastim either proactively or reactively. The primary endpoint was the proportion of patients experiencing febrile neutropenia. RESULTS: There were 852 patients enrolled (median age, 72 years). Proactive pegfilgrastim use resulted in a significantly lower incidence of febrile neutropenia for both solid tumor and NHL patients compared with reactive use. Proactive pegfilgrastim use also led to fewer hospitalizations resulting from neutropenia and febrile neutropenia by approximately 50%. Antibiotic use was lower for solid tumor patients receiving proactive pegfilgrastim and equivalent in the two NHL groups. CONCLUSIONS: This is the largest, randomized, prospective trial evaluating growth factor support in typical elderly cancer patients. Proactive pegfilgrastim use effectively produced a lower incidence of febrile neutropenia and related events in elderly patients with either solid tumors or NHL receiving an array of mild to moderately neutropenic chemotherapy regimens. Pegfilgrastim should be used proactively in elderly cancer patients to support the optimal delivery of standard chemotherapy.     

Brain abscess due to Streptococcus acidominimus: first case report

BACKGROUND: Streptococcus acidominimus resembles Streptococcus viridans, but they can now be differentiated by phenotypic studies. Only a single previous case of pneumonia, pericarditis, and meningitis has been reported. CASE DESCRIPTION: We recently encountered a patient with brain abscess from which S acidominimus was isolated after initially being recorded as S viridans. Because 49% of all S viridans isolated from abscesses are resistant to beta-lactam antimicrobials, speciation is important as well as in vitro sensitivity testing. Streptococcus acidominimus is ordinarily sensitive to beta-lactams, and the use of ceftriaxone for 6 weeks successfully resulted in cure of the brain abscess. CONCLUSION: The use of speciation in treatment of S viridans should improve clinical outcomes.     

Music training leads to the development of timbre-specific gamma band activity

Oscillatory gamma band activity (GBA, 30-100 Hz) has been shown to correlate with perceptual and cognitive phenomena including feature binding, template matching, and learning and memory formation. We hypothesized that if GBA reflects highly learned perceptual template matching, we should observe its development in musicians specific to the timbre of their instrument of practice. EEG was recorded in adult professional violinists and amateur pianists as well as in 4- and 5-year-old children studying piano in the Suzuki method before they commenced music lessons and 1 year later. The adult musicians showed robust enhancement of induced (non-time-locked) GBA, specifically to their instrument of practice, with the strongest effect in professional violinists. Consistent with this result, the children receiving piano lessons exhibited increased power of induced GBA for piano tones with 1 year of training, while children not taking lessons showed no effect. In comparison to induced GBA, evoked (time-locked) gamma band activity (30-90 Hz, approximately 80 ms latency) was present only in adult groups. Evoked GBA was more pronounced in musicians than non-musicians, with synchronization equally exhibited for violin and piano tones but enhanced for these tones compared to pure tones. Evoked gamma activity may index the physical properties of a sound and is modulated by acoustical training, while induced GBA may reflect higher perceptual learning and is shaped by specific auditory experiences.     

The burden of type 2 diabetes mellitus in states of the European Union and United Kingdom at the national and subnational levels: A systematic review

Type 2 diabetes mellitus (T2D) is a highly prevalent disease worldwide, with an equally increased expenditure associated with it. We aimed to longitudinally evaluate the epidemiologic and economic burden of T2D in the current member states of the European Union and the United Kingdom (EU-28). The present systematic review is registered on PROSPERO (CRD42020219894), and it followed the PRISMA guidelines. Eligibility criteria comprised original observational studies in English reporting economic and epidemiological data for T2D in member states of the EU-28. Methodological assessment was performed with the Joanna Briggs Institute (JBI) Critical Appraisal Tools. The search retrieved 2253 titles and abstracts. After study selection, 41 studies were included in the epidemiologic analysis and 25 in the economic analysis. Economic and epidemiologic studies covered only 15 member states with reported data between 1970 and 2017, resulting in an incomplete picture. For children in particular, limited information is available. The prevalence, incidence, mortality, and expenditure of the T2D population have increased across the decades in member states. Therefore, policies should aim to prevent or reduce the burden of T2D in the EU and consequently mitigate the expenditure on T2D.