Miracle-dz/UniFAR-FTUs huggingface dataset:
GGA Proteins Mediate the Recycling Pathway of Memapsin 2 (BACE)*

Memapsin 2 (BACE, β-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of β-amyloid precursor protein (APP) leading to the production of amyloid-β (Aβ) and the progression of Alzheimer disease. Both memapsin 2 and APP are transported from the cell surface to endosomes where APP is cleaved by memapsin 2. We described previously that the cytosolic domain of memapsin 2 contains an acid cluster-dileucine motif (ACDL) that binds the VHS (Vps-27, Hrs, and STAM) domain of Golgi-localized γ-ear-containing ARF-binding (GGA) proteins (He, X., Zhu, G., Koelsch, G., Rodgers, K. K., Zhang, X. C., and Tang, J. (2003) Biochemistry 42, 12174–12180). Here we report that GGA proteins colocalize in the trans-Golgi network and endosomes with memapsin 2 and a memapsin 2 chimera containing a cytosolic domain of a mannose-6-phosphate receptor. Depleting cellular GGA proteins with RNA interference or mutation of serine 498 to stop the phosphorylation of ACDL resulted in the accumulation of memapsin 2 in early endosomes. A similar change of memapsin 2 localization also was observed when a retromer subunit, VPS26, was depleted. These observations suggest that GGA proteins function with the phosphorylated ACDL in the memapsin 2-recycling pathway from endosomes to trans-Golgi on the way back to the cell surface.
Bacterial meningitis: pathogenesis, pathophysiology, and progress.

FIFTY years after the advent of antibiotics for clinical use, bacterial meningitis remains an important cause of morbidity and mortality. As such, it represents a unique human infectious disease, because the pathophysiologic effects of disease progression and suboptimal outcomes occur despite bacteriologic cure of the infection.1 Specifically, the mortality rate for adults who have Streptococcus pneumoniae meningitis remains 20 to 30 percent,2 , 3 with neurologic morbidity affecting half of survivors.4 The incidence of persistent sensorineural hearing loss in children who survive bacterial meningitis is 10 percent (31 percent of those with S. pneumoniae are affected) — a finding with critical implications .
The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration

Summary Active site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.
Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion for Labor Analgesia: The Effects on Maternal Motor Function and Labor Outcome. A Randomized Double-Blind Study in Nulliparous Women

BACKGROUND:Programmed intermittent epidural anesthetic bolus (PIEB) technique may result in reduced total local anesthetic consumption, fewer manual boluses, and greater patient satisfaction compared with continuous epidural infusion (CEI). In this randomized, double-blind study, we compared the incidence of motor block and labor outcome in women who received PIEB or CEI for maintenance of labor analgesia. The primary outcome variable was maternal motor function and the secondary outcome was mode of delivery. METHODS:Nulliparous, term women with spontaneous labor and cervical dilation <4 cm were eligible to participate in the study. Epidural analgesia was initiated and maintained with a solution of levobupivacaine 0.0625% with sufentanil 0.5 &mgr;g/mL. After an initial epidural loading dose of 20 mL, patients were randomly assigned to receive PIEB (10 mL every hour beginning 60 minutes after the initial dose) or CEI (10 mL/h, beginning immediately after the initial dose) for the maintenance of analgesia. Patient-controlled epidural analgesia (PCEA) using a second infusion pump with levobupivacaine 0.125% was used to treat breakthrough pain. The degree of motor block was assessed in both lower extremities using the modified Bromage score at regular intervals throughout labor; the end point was any motor block in either limb. We also evaluated PCEA bolus doses and total analgesic solution consumption. RESULTS:We studied 145 subjects (PIEB = 75; CEI = 70). Motor block was reported in 37% in the CEI group and in 2.7% in the PIEB group (P < 0.001; odds ratio = 21.2; 95% CI: 4.9–129.3); it occurred earlier (P = 0.008) (hazard ratio = 7.8; 95% CI: 1.9–30.8; P = 0.003) and was more frequent at full cervical dilation in the CEI group (P < 0.001). The incidence of instrumental delivery was 20% for the CEI group and 7% for the PIEB group (P = 0.03). Total levobupivacaine consumption, number of patients requiring additional PCEA boluses, and mean number of PCEA boluses per patient were lower in the PIEB group (P < 0.001). No differences in pain scores and duration of labor analgesia were observed. CONCLUSIONS:Maintenance of epidural analgesia with PIEB compared with CEI resulted in a lower incidence of maternal motor block and instrumental vaginal delivery.
Evaluation of the Efficacy of an Insecticidal Paint Based on Chlorpyrifos and Pyriproxyfen in a Microencapsulated Formulation Against Rhynchophorus ferrugineus (Coleoptera: Curculionidae)

ABSTRACT The weevil Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) is an important pest of palms. It has recently colonized the Mediterranean Basin where it is a serious problem on ornamental Phoenix canariensis (hort. ex Chabaud) palms. The efficacy of an insecticidal paint based on chlorpyrifos and pyriproxyfen in a microencapsulated formulation (Inesfly IGR FITO, Industrias Químicas Inesba S.L., Paiporta, Spain) against this weevil has been studied, Laboratory results proved that pyriproxyfen has no effect against R. ferrugineus when applied in this microen-capsulated formulation, Semifield trials dismissed Inesfly IGR FITO as a curative insecticide but showed the potential of this product in the preventative control of R. ferrugineus in palms. One single application could prevent infestation for up to 6 mo with a mean efficacy of 83.3%.
Attainment and reflection : the role of social capital and regrets in developmental regulation

Jokisaari, Markku Attainment and reflection: The role of social capital and regrets in developmental regulation Jyväskylä: University of Jyväskylä, 2007, 61 p. (Jyväskylä Studies in Education, Psychology and Social Research, ISSN: 0075-4625; 321) ISBN: 978-951-39-2978-7 (nid.), 978-951-39-5173-3 (PDF) Diss. Developmental regulation reflects both individuals' proactive attempts to influence their own life course and their reactive efforts to adapt and accept their circumstances and reconstruct their goals and aspirations accordingly. In this study I focused on both proactive and reactive aspects of developmental regulation. First, I argue that goal-related social capital plays an important role in proactive developmental regulation and related goal attainment. In other words, social capital theory and the related network approach emphasize that a person's success depends on how she or he is located in networks and what kind of resources these networks enable for a focal person's aims. Using longitudinal data on recent graduates, the present study investigated the social ties involved in recent graduates' work-related goals and whether social ties contribute to success in dealing with the transition. The results showed that social ties that included a person with high socioeconomic status and weaker ties contributed to success in employment, whereas social ties including one's supervisor were associated with quality of employment. The results suggest that social ties are often a source of resources which enables a person to maintain his or her proactive developmental regulation and attain his or her goals. Secondly, I examined reactive developmental regulation, which pertains to how people regulate and evaluate unattained goals and goals with unintended consequences, i.e. regrets, and how such evaluation is related to well-being. Specifically, I examined whether regrets would be related to age and subjective well-being in a sample of participants ranging in age 19 to 82 years. The results showed that those who appraised their regret-related goals or events as having an impact on their present lives reported a lower level of life satisfaction and more physical symptoms than those who appraised their regrets as having less consequence. The results further showed that regrets concerning education and work were negatively related to satisfaction with life. There were also age differences in regret appraisals and contents. In all, this study suggests that through social capital theory and related network approach it is possible to expand psychological models on developmental regulation.
Bedside Chest Radiography Using Digital Luminescence

The introduction of picture and archiving communicating systems is currently being evaluated in several institutions. We decided, as an intermediate step, to see if image quality after transferral to a personal computer (PC) is sufficient for the diagnostic needs in an intensive care unit. Seventy-five portable digital chest radiographs were studied both as hard-copies and on a monitor after transferral to a PC. Two chest radiologists and one anesthesiologist reviewed the examinations. Our intention was to evaluate if everything that is routinely checked by the anesthesiologist is demonstrable after electronic transfer to a local workstation. We found practically no difference between the performance of monitor and film for the whole material.
Nonoperative management of dens fracture nonunion in elderly patients without myelopathy.

STUDY DESIGN A retrospective review of elderly patients treated without surgery for chronic mobile nonunions of the odontoid process. Patients were observed on an annual basis with clinical examinations and flexion/extensions plain film radiographs. OBJECTIVES To evaluate the clinical and radiographic results of elderly patients without myelopathy treated without surgery for dens fracture nonunion. SUMMARY OF BACKGROUND DATA Because of the risk of progressive myelopathy or sudden neurologic injury, many surgeons recommend operative stabilization for patients with mobile dens nonunions who are able to withstand an operation. There is, however, a lack of information about the radiographic and neurologic progression of dens nonunions. Although a less aggressive surgical approach has been recommended by some authors for elderly or medically compromised patients with acute fractures, long-term follow-up evaluation of patients with resulting nonunions has not been reported. METHODS A series of elderly patients with chronic, unstable, dens nonunions without myelopathy were treated with a nonoperative treatment protocol. Patients were informed of the nature of their lesion, including the risk of acute or chronic spinal cord injury and the options for operative treatment. Patients were evaluated yearly for clinical and radiographic progression. No intervention to slow progression of atlantoaxial instability was undertaken. RESULTS None of the patients developed myelopathic symptoms during the follow-up period, and no patient experienced more than a 1 mm radiographic increase in atlantoaxial excursion. None of the reported patients had less than 14 mm available for the spinal cord in either flexion or extension at the start of clinical monitoring. CONCLUSIONS Although further follow-up evaluation is needed, the authors believe on the basis of this review that this treatment protocol may be considered for patients who are poor candidates for surgical fusion.
In vitro Evaluation of Antileishmanial Activity and Toxicity of Essential Oils of Artemisia absinthium and Echinops kebericho

Potential toxicity, costs, and drug‐resistant pathogens necessitate the development of new antileishmanial agents. Medicinal and aromatic plants constitute a major source of natural organic compounds. In this study, essential oils of Artemisia absinthium L. and Echinops kebericho Mesfin were investigated by GC and GC/MS analyses. Isolated oils were screened for antileishmanial activity against two Leishmania strains (L. aethiopica and L. donovani), and toxicity on the human monocytic leukemia (THP‐1) cell line and red blood cells in vitro. GC/MS Analysis revealed 65 compounds (93.74%) for Artemisia absinthium and 43 compounds (92.85%) for Echinops kebericho oil. The oils contained the oxygenated monoterpene camphor (27.40%) and the sesquiterpene lactone dehydrocostus lactone (41.83%) as major constituents, respectively. Both oils showed activity against promastigote (MIC 0.0097–0.1565 μl/ml) and axenic amastigote forms (EC50 0.24–42.00 nl/ml) of both leishmania species. Weak hemolytic effect was observed for both oils, showing a slightly decreased selectivity index (SI 0.8–19.2) against the THP‐1 cell line. Among the two oils tested, E. kebericho exerted strong antileishmanial activity that was even higher than that of amphotericin B with significant cytotoxicity. This study, therefore, demonstrated the potential use of both oils as source of novel agents for the treatment of leishmaniasis.
Age‐dependent variation in the serum concentration of mannan‐binding protein

Mannan‐binding protein (MBP) is an acute phase reactant, and its deficiency is associated with the common opsonic defect and suspectibility to infections and atopic constitution. The aim of this study was to investigate the changes occurring in the serum level of MBP in infancy and during later childhood. We studied the serum concentration of MBP in 611 Finnish children of different ages and 110 adults by using an enzyme immunoassay. In an analysis of successive serum samples from infants at the day of birth and at the ages of 1 and 5 months, and at 1 and 2 years, the serum concentration of MBP increased significantly after birth, and was at its highest (the mean and median were 8.13 and 8.49 mg1−1, respectively) at the age of 1 month. After that, it declined to the initial level until the age of 5 months. The MBP concentration continued to decrease during childhood, and after the age of 12 years the MBP values reached the adult level. In Finnish adults the mean and median concentrations of MBP were 4.48 and 4.02 mg 1−1, respectively, which seem to be higher than those reported previously in other populations. The high concentration of MBP in infants may best be explained by exposure to novel environmental antigens in early childhood, which suggests a protective role for MBP during the period of immaturity of the immunosystem. In older children the high level of MBP can probably be explained by childhood infections and the ensuing need of MBP.
Altering the temporal distribution of energy intake with isoenergetically dense foods given as snacks does not affect total daily energy intake in normal-weight men

The objectives of the present study were to examine the effects of (1) ingesting mandatory snacks v. no snacks and (2) the composition of isoenergetically-dense snacks high in protein, fat or carbohydrate, on food intake and energy intake (EI) in eight men with ad libitum access to a diet of fixed composition. Subjects were each studied four times in a 9 d protocol per treatment. On days 1–2, subjects were given a medium-fat maintenance diet estimated at 1·6 × resting metabolic rate (RMR). On days 3–9, subjects consumed three mandatory isoenergetic, isoenergetically dense (380 kJ/100 g) snacks at fixed time intervals (11.30, 15.30 and 19.30 hours). Total snack intake comprised 30 % of the subjects' estimated daily energy requirements. The treatments were high protein (HP), high carbohydrate (HC), high fat (HF) and no snack (NS). The order was randomized across subjects in a counterbalanced, Latin-square design. During the remainder of the day, subjects had ad libitum (meal size and frequency) access to a covertly manipulated medium-fat diet of fixed composition (fat: carbohydrate: protein, 40:47:13 by energy), energy density 550 kJ/100 g. All foods eaten were investigator-weighed before ingestion and left-overs were weighed after ingestion. Subjective hunger and satiety feelings were tracked hourly during waking hours using visual analogue scales. Ad libitum EI amounted to 13·9 MJ/d on the NS treatment compared with 11·7, 11·7 and 12·2 MJ/d on the HP, HC and HF diets respectively (F(3,21) 5·35; P = 0·007, sed 0·66). Total EI values were not significantly different at 14·6, 14·5, 15·0 and 14·2 MJ/d respectively. Snack composition did not differentially affect total daily food intake or EI. Average daily hunger was unaffected by the composition of the snacks. Only at 12.00 hours did subjects feel significantly more hungry during the NS condition, relative to the other dietary treatments (F(3,18) 4·42; P = 0·017). Body weight was unaffected by dietary treatment. In conclusion, snacking per se led to compensatory adjustments in feeding behaviour in lean men. Snack composition (with energy density controlled) did not affect the amount eaten of a diet of fixed composition. Results may differ in real life where subjects can alter both composition and amount of food they eat and energy density is not controlled.
Cancer in East Azerbaijan, Iran: results of a population-based cancer registry.

BACKGROUND AND AIMS Regardless of the fact that cancers of GI tract have been reported to be the most common fatal neoplasms in East Azerbaijan, there is a serious lack of population-based studies in this region. METHODS A comprehensive search was therefore undertaken to prospectively register all cases of cancer occurring in the province during March 2006-2007. Diagnosis of cancer was based on histopathology of primary lesions in 84.0% of cases, clinical investigation and ultrasound in 7.2%, only clinical investigation in 5.4%, and histology of metastasis in 2.9. Less than 1% were based on cytology and death certificates in one official year. RESULTS A total of 4,922 cancers (mean age 60.2+18.13 years) were diagnosed during this population-based study. Of these, 56.8% (2114) were in males. ASRs for all cancers in males and females were 164.3 and 130.6 respectively. The top five sites for cancer in males (excluding skin cancer) according to the calculated ASR (world) were stomach (26.0), bladder (15.7), esophagus (12.4), colon and rectum (11.6) and blood (10.8); in females, they were breast (23.5), esophagus (11.7), stomach (11.6), colon and rectum (9.7) and nervous system (5.5). CONCLUSION This first comprehensive report on cancer incidence in East Azerbaijan, documents particularly high incidence rates for esophageal and gastric cancer across the sexes.
A Causal Model of Depression in Early Adolescents

The purpose of this study was to test the extent to which a causal model developed from a theoretical formulation of depression was consistent with data obtained from early adolescents, age 12 to 14. In this cross-sectional correlational design, the final sample consisted of 225 adolescents who responded to a demographic data sheet and instruments measuring depression, self-esteem, state anxiety, and perceived stress in classrooms. The causal model was tested via the LISREL 7 program, using a maximum likelihood structural equation model. The results yielded a chi-square (1, N = 225) = . 71, p =. 401, indicating a good fit of the model to the data. Perceived stress had the strongest direct, indirect, and total effect on depression in early adolescents. Contrary to expectation, self-esteem did not have a direct effect on depression, and girls did not report higher levels of depression than did boys.
Autotransplantation of the adrenal cortex: A morphological and autoradiographic study

A morphological and autoradiographic study was made of the adrenal gland of adult male rats after autotransplantation. The simple technique involved placement of pieces of the adrenal gland in a dorsal plane between the skin and muscle. Animals for morphological studies were sacrificed at 2, 3, 4, 7, 15, 30, 90, and 180 days after autotransplantation. Those for autoradiographic studies were sacrificed at 2, 3, 7, and 15 days after autotransplantation, with 3H‐thymidine being administered intraperitoneally 2 h before sacrifice. Sham‐operated animals were used as controls. The majority of glandular adrenal cells suffered necrosis in the first days (2 and 3) after autotransplantation. Up until 15 days and after revascularization, morphological features of the cells were compatible with protein synthesis exhibiting a developed RER, scarce SER, and mitochondria with tubular and lamellar cristae. These data may correspond to a proliferative phase of glandular cells. At day 15, cells showed morphological signs of steroidogenic activity (mitochondria with vesicular cristae, increase of SER), and at day 30, an increased number of microvilli were seen. Between 30 and 90 days zonation of the adrenal was evident with glomerulosa, fasciculata, and reticular zones readily apparent. The quantitative analysis showed a significant increase of the volumetric density of mitochondria and microvilli between the days 7 and 30.
Identification of Borrelia burgdorferi Outer Surface Proteins

ABSTRACT Several Borrelia burgdorferi outer surface proteins have been identified over the past decade that are up-regulated by temperature- and/or mammalian host-specific signals as this spirochete is transmitted from ticks to mammals. Given the potential role(s) that these differentially up-regulated proteins may play in B. burgdorferi transmission and Lyme disease pathogenesis, much attention has recently been placed on identifying additional borrelial outer surface proteins. To identify uncharacterized B. burgdorferi outer surface proteins, we previously performed a comprehensive gene expression profiling analysis of temperature-shifted and mammalian host-adapted B. burgdorferi. The combined microarray analyses revealed that many genes encoding known and putative outer surface proteins are down-regulated in mammalian host-adapted B. burgdorferi. At the same time, however, several different genes encoding putative outer surface proteins were found to be up-regulated during the transmission and infection process. Among the putative outer surface proteins identified, biochemical and surface localization analyses confirmed that seven (Bb0405, Bb0689, BbA36, BbA64, BbA66, BbA69, and BbI42) are localized to the surface of B. burgdorferi. Furthermore, enzyme-linked immunosorbent assay analysis using serum from tick-infested baboons indicated that all seven outer surface proteins identified are immunogenic and that antibodies are generated against all seven during a natural infection. Specific antibodies generated against all seven of these surface proteins were found to be bactericidal against B. burgdorferi, indicating that these newly identified outer surface proteins are prime candidates for analysis as second-generation Lyme disease vaccinogens.