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991.
  1. Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.

  2. Here, our aim was to study the interaction between BChE and fluoxetine.

  3. Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59?±?0.36?U mg?1 protein, 194?±?14?µM, 1.3?×?108?s?1 and 6.7?×?105?µM?1s?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104?µM and a Ki value of 36.3?±?4.7?µM.

  4. Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.

  相似文献   
992.

Objectives

Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

Design and participants

Twenty-six older patients (75 ± 1 years) undergoing elective total hip arthroplasty participated in this observational study.

Measurements

On hospital admission and on the day of discharge, computed tomographic (CT) scans were performed to assess muscle cross-sectional area (CSA) of both legs. During surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken from the m. vastus lateralis of the operated leg to assess muscle fiber type–specific CSA.

Results

An average of 5.6 ± 0.3 days of hospitalization resulted in a significant decline in quadriceps (?3.4% ± 1.0%) and thigh muscle CSA (?4.2% ± 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% ± 1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission, muscle fiber CSA was smaller in the type II vs type I fibers (3326 ± 253 μm2 vs 4075 ± 279 μm2, respectively; P < .05). During hospitalization, type I and II muscle fiber CSA tended to increase, likely due to edema in the operated leg (P = .10).

Conclusions

Six days of hospitalization following elective total hip arthroplasty leads to substantial leg muscle atrophy in older patients. Effective intervention strategies are warranted to prevent the loss of muscle mass induced by short periods of muscle disuse during hospitalization.  相似文献   
993.
Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.  相似文献   
994.
BACKGROUND AND PURPOSE:Cervical spine axial MRI T2-hyperintense fluid signal of the anterior median fissure and round hyperintense foci resembling either the central canal or base of the anterior median fissure are associated with a craniocaudad sagittal line, also simulating the central canal. On the basis of empiric observation, we hypothesized that hyperintense foci, the anterior median fissure, and the sagittal line are seen more frequently in patients with Chiari malformation type I, and the sagittal line may be the base of the anterior median fissure in some patients.MATERIALS AND METHODS:Saggital line incidence and the incidence/frequency of hyperintense foci and anterior median fissure in 25 patients with Chiari I malformation and 25 contemporaneous age-matched controls were recorded in this prospective exploratory study as either combined (hyperintense foci+anterior median fissure in the same patient), connected (anterior median fissure extending to and appearing to be connected with hyperintense foci), or alone as hyperintense foci or an anterior median fissure. Hyperintense foci and anterior median fissure/patient, hyperintense foci/anterior median fissure ratios, and anterior median fissure extending to and appearing to be connected with hyperintense foci were compared in all, in hyperintense foci+anterior median fissure in the same patient, and in anterior median fissure extending to and appearing to be connected with hyperintense foci in patients with Chiari I malformation and controls.RESULTS:Increased sagittal line incidence (56%), hyperintense foci (8.5/patient), and anterior median fissure (4.0/patient) frequency were identified in patients with Chiari I malformation versus controls (28%, 3.9/patient, and 2.7/patient, respectively). Increased anterior median fissure/patient, decreasing hyperintense foci/anterior median fissure ratio, and increasing anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified in Chiari subgroups. A 21%–58% increase in observed anterior median fissure extending to and appearing connected to hyperintense foci in the entire cohort and multiple sagittal line subgroups compared with predicted occurred.CONCLUSIONS:In addition to the anticipated increased incidence/frequency of sagittal line and hyperintense foci in patients with Chiari I malformation, an increased incidence and frequency of anterior median fissure and anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified. We believe an anterior median fissure may contribute to a saggital line appearance in some patients with Chiari I malformation. While thin saggital line channels are usually ascribed to the central canal, we believe some may be due to the base of the anterior median fissure, created by pulsatile CSF hydrodynamics.

Axial MR imaging of the cervical spine frequently demonstrates hyperintense, linear, anatomically, sagittally-oriented T2 fluid signal of the anterior median fissure (AMF) and hyperintense foci (HIF) resembling the central canal or the base of the AMF.1-3 These axial T2 findings may be associated with a channel-like T2-hyperintense craniocaudad line on images parallel to the sagittal plane (a sagittal line [SL]), simulating the central canal (Fig 1).4,5 A previous analysis of HIF, AMF, and a thin SL in a population without Chiari I malformation provided not only a baseline for their identification but also a confirmation of a relationship between not only the AMF and HIF but also their relationship to the SL.1 It found the following:
  1. HIF were greater in number than AMFs, but AMFs increase in the presence of increasing HIF, suggesting an anatomic relationship.
  2. SLs were associated with greater numbers of both HIF and AMF/patient (pt.) versus no SL, 6.7 versus 2.7/pt. and 3.3 versus 2.0/pt., respectively. SL presence correlated more closely to HIF than to AMF presence within the entire 358-patient group.
  3. When HIF and AMF were classified as combined (concurrent HIF and AMF, with ≥1 of each both present in the same patient [HIF+AMF]) or continuous (AMF appearing to extend to and join an HIF [AMF>HIF]), HIF and AMF/pt. each differed numerically and patients with an SL had more combined HIF+AMF and continuous AMF>HIF than patients without an SL.
  4. In patients with both SL and combined HIF+AMF (a circumstance allowing the possibility of a relationship of all 3 structures), HIF become proportionally fewer compared with AMFs. In patients with an SL actually exhibiting continuous AMF>HIF, the HIF/AMF ratio decreased further.
Open in a separate windowFIG 1.A patient with Chiari I with 19 HIF up to 3 mm in diameter, 1 AMF, no AMF>HIF, and an SL of various hyperintensity and diameter from C4 through T1, consistent with hydromyelia.While it is expected that manifestations of the central canal as an SL and HIF are more frequent in patients with Chiari syndrome type I,6 past experience leads us to hypothesize that AMFs are also seen more frequently in patients with Chiari I malformation and that the SL or channel may represent the base of a wide AMF, rather than the central canal, in some patients (Figs 1 and and2).2). Therefore, we performed an exploratory prospective analysis of HIF, AMF, and SL in patients with Chiari I malformation to examine their relationships.Open in a separate windowFIG 2.Postdecompressive craniectomy patient with Chiari I with 9 HIF, 4 AMFs, 1 AMF>HIF, and sharp and hyperintense SLs at C6–C7 and less hyperintense, sharp, and defined SLs at C2–C6.  相似文献   
995.

Objectives

This study aimed to explore the genetic diversity of Streptococcus pneumoniae isolates in a Tunisian pneumology hospital.

Methods

A total of 141 S. pneumoniae strains isolated between 2009–2016 in the microbiology laboratory at A. Mami Hospital of Pneumology were investigated. Antimicrobial susceptibility testing was performed the disk diffusion method. MICs of penicillin G, amoxicillin and cefotaxime were determined by Etest. Serotyping was inferred from the results of multiplex PCR targeting 40 serotypes. Sequence types (STs) were determined by multilocus sequence typing (MLST).

Results

Among the 141 S. pneumoniae isolates, 98 (69.5%) were resistant to erythromycin. Evaluation of β-lactam susceptibility showed that 90 strains (63.8%) were non-susceptible to penicillin, whereas 48 (34.0%) had decreased susceptibility to amoxicillin and 21 (14.9%) to cefotaxime. Twenty-five serotypes were detected, and 10 isolates were classified as non-typeable. Vaccine coverage was 56.7%, 60.3% and 75.2% for pneumococcal conjugate vaccine 7 (PCV7), PCV10 and PCV13, respectively. Overall, 73 STs were identified, including 23 described for the first time. The most frequent STs were ST179 (n?=?17), ST3772 (n?=?14), ST2918 (n?=?10) and ST4003 (n?=?5), related to serotypes 19F, 19A, 14 and 23F, respectively. Moreover, 110 strains were classified within 45 STs. Three international antimicrobial-resistant clones were found, including Denmark14-ST230 (n?=?22), Spain9V-ST156 (n?=?22) and Portugal19F-ST177 (n?=?20).

Conclusion

This study emphasises the clonal and international dissemination of antimicrobial-resistant S. pneumoniae clones. Significant differences in genetic variation were documented by MLST within the various serotypes identified.  相似文献   
996.
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Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.  相似文献   
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