Two arginine kinases of Tetrahymena pyriformis: characterization and localization.
Two cDNAs, one coding a typical 40-kDa arginine kinase (AK1) and the other coding a two-domain 80-kDa enzyme (AK2), were isolated from ciliate Tetrahymena pyriformis, and their recombinant enzymes were successfully expressed in Escherichia coli. Both enzymes had an activity comparable to those of typical invertebrate AKs. Interestingly, the amino acid sequence of T. pyriformis AK1, but not AK2, had a distinct myristoylation signal sequence at the N-terminus, suggesting that 40-kDa AK1 targets the membrane. Moreover, Western blot analysis showed that the AK1 is mainly localized in the ciliary fraction. Based on these results, we discuss the phosphoarginine shuttle, which enables a continuous energy flow to dynein for ciliary movement in T. pyriformis, and the role of AK1 in this model.


Establishment and maintenance of HSV latent infection is mediated through correct splicing of the LAT primary transcript.
To study the effect of the splicing of HSV-1 latency-associated transcript (LAT) on viral latency, we constructed two mutant viruses (FHlambda+ and FHlambda-) in which the 168-bp HpaI-HpaI fragment within the 2-kb LAT intron was replaced by a 447-bp bacteriophage lambda sequence. The lambda DNA was inserted in opposite orientations in FHlambda+ and FHlambda-. The mutation in FHlambda+ disrupted the splicing of LAT primary transcript and altered both LAT exon and intron, whereas the mutation in FHlambda- virus preserved the wild-type splice sites and the wild-type exon. Quantitative PCR analysis revealed that during latency there was a reduction in the number of viral genomes in mouse trigeminal ganglia infected with FHlambda+ but not in those infected with FHlambda-. The decrease in the latent genome numbers was not due to a defect in viral replication during the acute stage of infection. Furthermore, trigeminal ganglia from mice latently infected with FHlambda+ displayed a slower reactivation kinetics compared to those infected with the parental strain. To elucidate the mechanism, we examined the antiapoptotic properties of these LAT constructs. A plasmid containing the pHlambda+ construct was found to be less protective for cells against apoptosis than plasmid containing the wild-type or pHlambda- constuct. These results suggest that the splicing of LAT primary transcript, and thus the correctly spliced exon product, play an important role in promoting the establishment and/or maintenance of viral latency.


Involvement of endogenous cholecystokinin in tolerance to morphine antinociception in the nucleus accumbens of rats.
Cholecystokinin (CCK) is an endogenous anti-opioid peptide in the central nervous system. The present study investigated the effects of endogenous CCK on tolerance to morphine antinociception in the nucleus accumbens (NAc) of rats. Chronic administration of morphine to NAc induced marked tolerance to antinociception. Intra-NAc administration of the CCK2 receptor antagonist LY225910 inhibited not only the development but also the expression of chronic morphine-induced antinociceptive tolerance. However, intra-NAc injection of LY225910 did not influence the antinociception induced by intra-NAc administration of morphine in the intact rats. The results indicate that endogenous CCK plays an important role in morphine-induced antinociceptive tolerance in the NAc of rats.


The prevalence and management of deteriorating patients in an Australian emergency department.
Complex human and system factors impact the effectiveness of Rapid Response Systems (RRS). Emergency Department (ED) specific RRS are relatively new and the factors associated with their effectiveness are largely unknown. This study describes the period prevalence of deterioration and characteristics of care for deteriorating patients in an Australia ED and examine relationships between system factors and escalation of care. A retrospective medical record audit of all patients presenting to an Australian ED in two weeks. Period prevalence of deterioration was 10.08% (n=269). Failure to escalate care occurred in nearly half (n=52, 47.3%) of the patients requiring a response (n=110). Appropriate escalation practices were associated with where the patient was being cared for (p=0.01), and the competence level of the person documenting deterioration (p=0.005). Intermediate competence level nurses were nine times more likely to escalate care than novices and experts (p=0.005). While there was variance in escalation practice related to system factors, these associations were not statistically significant. The safety of deteriorating ED patients may be improved by informing care based on the escalation practices of staff with intermediate ED experience and competence levels.


Effects of two pyridinalalkyliminerhodium(I) complexes in mice bearing MCa mammary carcinoma.
The examination of the differential effects of two square-planar rhodium(I) complexes on primary tumor growth and on the formation of spontaneous and artificially (i.v. tumor injection) induced lung metastases of MCa mammary carcinoma suggests different mechanisms of action, depending on the chemical characteristics of the compound used. Of the two complexes used, cyclooctadiene(2-pyridinalmethylimine)Rh(I) chloride and cyclooctadiene(2-pyridinalisopropylimine)Rh(I) chloride, the former compound confirmed the antineoplastic action previously shown in the Lewis lung carcinoma model. The activity of this derivative on lung metastasis formation seems to be unrelated to a cytotoxic action for tumor cells localized in the lungs. More likely, it appears that modifications occurring at the primary tumor level, probably different from a tumor-cell-directed lethality, are responsible for the reduction of spontaneous lung metastasis formation observed in treated animals. The hyperplasia of the spleen induced in treated animals seems to suggest that this compound is endowed with properties typical for biological response modifiers.


Effects of feeding Oxytropis and Astragalus pollen to mice and Astragalus seeds to rats.
Pollens collected from Astragalus lentiginosus and Oxytropis sericea were fed to mice. At the end of the feeding period, uterine weights were taken to determine estrogenic activity, and tissue was collected for microscopic examination. The pollen from A lentiginosus, but not from O sericea, induced lesions similar to those of locoweed poisoning. The pollen from neither plant was estrogenic. Seeds from A lentiginosus produced toxicosis when fed to rats.


Computational biomechanical modelling of the lumbar spine using marching-cubes surface smoothened finite element voxel meshing.
There is a need for the development of finite element (FE) models based on medical datasets, such as magnetic resonance imaging and computerized tomography in computation biomechanics. Direct conversion of graphic voxels to FE elements is a commonly used method for the generation of FE models. However, conventional voxel-based methods tend to produce models with jagged surfaces. This is a consequence of the inherent characteristics of voxel elements; such a model is unable to capture the geometries of anatomical structures satisfactorily. We have developed a robust technique for the automatic generation of voxel-based patient-specific FE models. Our approach features a novel tetrahedronization scheme that incorporates marching-cubes surface smoothing together with a smooth-distortion factor (SDF). The models conform to the actual geometries of anatomical structures of a lumbar spine segment (L3). The resultant finite element analysis (FEA) at the surfaces is more accurate compared to the use of conventional voxel-based generated FE models. In general, models produced by our method were superior compared to that obtained using the commercial software ScanFE.


Zoledronic acid for osteoporosis after distal radius fracture surgery.
Distal radius fractures (DRFs) are the most frequent first-ever osteoporotic fragility fractures. However, most patients are treated only for fractures and not for osteoporosis. Therefore, we investigated early osteoporosis intervention using zoledronic acid. This prospective study enrolled 30 patients aged 50 years or older who had no history of fragility fractures or osteoporosis treatment and who underwent surgical treatment for DRFs. Patients whose lumbar spine or femur bone mineral density (BMD) values were less than 80% of the young adult mean (YAM) were treated with a 5-mg intravenous infusion of zoledronic acid. Lumbar spine and femur YAM BMD values, TRACP-5b and PINP were statistically evaluated using the paired t-test. The relationship between adverse effects, age, body mass index (BMI), and creatinine clearance (CCr) was statistically examined using Mann-Whitney's U test. The incidence of the bone fusion and secondary fractures within the 60-months postoperative period were assessed. The mean lumbar spine and femur YAM BMD values before treatment were 76.1 ± 13.1% and 70.7 ± 8.5%. This indicates osteopenia in both locations. These values differed significantly between the pre-treatment period and each subsequent period. Five patients with a target YAM BMD value over 80% within 60 months after treatment were observed. The TRACP-5b and PINP values differed significantly between the pre-treatment period and each subsequent period. Adverse drug reactions were observed in 12 patients (40%). Age, BMI, and CCr did not show statistically significant differences in the occurrence of adverse effects. Bone fusion was confirmed at a mean of 3.6 months postoperatively. Secondary fractures were observed in 3 patients within 60 months after treatment. DRFs occur at a younger age than other fragility fractures, and it is important to intervene aggressively with osteoporosis treatment to prevent secondary fractures. Level V.


The role of activated vascular angiotensin II generation in vascular hypertrophy in one-kidney, one clip hypertensive rats.
To investigate the role of vascular angiotensin II (Ang II) in the vascular thickening of one-kidney, one clip (1-K, 1C) hypertensive rats, which show normal plasma renin activity. The type 1 Ang II receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme (ACE) inhibitor delapril (20 mg/kg per day), hydralazine (20 mg/kg per day) or vehicle were administered to four groups of 1-K, 1C rats aged 6-10 weeks. Vehicle was also given to uninephrectomized rats. The aortae of 1-K, 1C rats contained significantly higher levels of Ang II than those of uninephrectomized rats and showed hypertrophy, but not hyperplasia of their medial smooth muscle cells. Hypertrophy was estimated by immunohistochemical staining of alpha-actin. Hyperplasia was estimated by DNA content and incorporation of 5-bromo-2'-deoxyuridine. The blood pressure of the 1-K, 1C rats was not affected by either TCV-116 or delapril, even at doses sufficient to induce depressor effects in spontaneously hypertensive rats. However, subdepressor doses of TCV-116 and delapril both significantly reduced the alpha-actin-stained area to 78 and 73%, respectively, of that in the 1-K, 1C rats, whereas a depressor dose of hydralazine did not affect the alpha-actin-stained area. The level of Ang II in the aorta, but not in plasma, was suppressed by delapril but not by hydralazine. These results suggest strongly that vascular Ang II plays a major role in the development of vascular hypertrophy, independently of plasma Ang II, bradykinin and ACE-independent pathways of Ang II generation, and in the regulation of blood pressure in this normoreninaemic hypertensive model.


Outcomes of retroperitoneal lymph node dissection for testicular cancer by a high volume surgeon from Australia: a case for centralisation.
There are few studies examining retroperitoneal lymph node dissection (RPLND) for testicular cancer in Australia. This study examines the perioperative outcomes, complications and survival rates following RPLND, by a high volume, single surgeon. A retrospective, case series of a single surgeon, multi-centre study included all patients who underwent RPLND following testicular cancer at Westmead Public Hospital, Westmead Private Hospital, and Macquarie University Hospital 2005-2020. One hundred one patients identified, with 94 having sufficient available data. At time of operation, median age was 29.5 years. 84.2% had T1 or T2 primary tumours at diagnosis. Most common RPLND indication was residual mass post-chemotherapy (92.6%), with bleomycin, etoposide and cisplatin (BEP)x3 and BEPx4 most common chemotherapy regimens (50% and 35% respectively). Post-chemotherapy, largest residual mass ranged from 0.9 to 20 cm (median 3.32 cm). Post-chemotherapy, 95.7% masses were found in retroperitoneum (64.4% para-aortic region). 93.6% had open approach. 42.5% had bilateral nerve sparing. Majority (97.1%) did not require blood transfusion. No complications reported in 52.1% of patients. No deaths recorded within 90 days of surgery. At time of analysis, 91.5% had recurrence free survival, and 92.6% overall survival, at a median follow-up since surgery of 47.5 months (range 11 to 200 months). This retrospective study, addressing peri-operative surgical outcomes for RPLND surgery in Australia, is comparable to high-volume international urological centre studies, and shows that centralisation of post-chemotherapy RPLND to an experienced surgeon, results in low perioperative morbidity and mortality.


Beta-Blockers, Digoxin, or Both Following an Incident Diagnosis of Atrial Fibrillation: A Prospective Cohort Study.
Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rate control strategy remains uncertain. A retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta-blockers, digoxin, or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovascular (CV) hospitalization. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model. A total of 12,723 patients were discharged on beta-blockers alone, 406 on digoxin alone, and 1499 discharged on combined beta-blocker and digoxin therapy with a median follow-up time of 356 days. After baseline covariate adjustment, the digoxin alone (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.85-1.81) and the combined group (HR, 1.09; 95% CI, 0.90-1.31) were not associated with increased risk for the composite endpoint compared with the beta- blocker-alone group. These results were robust to sensitivity analyses. Patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta-blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared with those discharged on isolated beta-blocker therapy. However, additional studies are required to refine the precision of these estimates.


[Osteoplastic procedure for cystic processes in posterior mandibular region].
This Report deals with surgical treatment of the extended osteolysis processes for the mandibular posterior tooth area. It will show the advantages of an osteoplastical method of operation. According to a case report the therapy of an extended solitary bone cyst will be carried out with an apisectomy of the molar 46 at the same time.


Coarse-grained simulations of the salt dependence of the radius of gyration of polyelectrolytes as models for biomolecules in aqueous solution.
The salt dependent radius of gyration of a polyelectrolyte in aqueous solution is calculated in an environment where the polyelectrolyte is surrounded by a permeable membrane that exchanges only solvent particles with the bulk. We obtain additionally the scaling exponent of the gyration radius as a function of the polymerization degree, and find that the polyelectrolyte retains a stretched conformation during the condensation and re-expansion process, indicating that these effects are of an electrostatic nature. The solvent quality is also shown to affect the polyelectrolyte conformation, especially for the poor solvent case. These results are obtained using a hybridized Monte Carlo technique with the coarse-grained, dissipative particle dynamics method with fluctuating number of solvent particles. The full range of the electrostatic interactions is included in the simulations, using the Ewald sum method, and the counterions and solvent molecules are included explicitly. In the complex systems mentioned above, the electrostatic interactions and the solvent quality play a key role in understanding phenomena that do not occur in uncharged systems. Our results are compared and validated with the behavior of some biomolecules under similar environments.


[Myocardial revascularization after pretreatment with the GPIIb/IIIa receptor blocker abciximab].
The present prospective study analysis whether preoperative abciximab treatment 1) increases perioperative risks, 2) alters the quality of the surgical treatment, 3) whether secondary organ complications occur and 4) whether and how the perioperative surgical management has to be modified. The perioperative results of patients operated upon after preoperative abciximab treatment (n = 31, 1/1994-4/2000) were compared with an optimal control group (elective patients and no preoperative intervention in the hemostaseological system) and with other patients (elective, urgent, emergency operations) receiving different strategies of preoperative hemostaseological interventions (n = 926, 1/1994-4/2000). All patients were operated upon with a well-defined strategy (one surgeon). 1100 perioperative items/patient were prospectively recorded and analyzed. The 30-day and 6 month follow-up was complete. The mean time interval between end of abciximab therapy and onset of operation was 4.3 h (range: 36-0.5 h, median: 2 h). As compared with the optimal control group (n = 81), perioperative blood loss and the need for substitution of blood and blood products was increased. However, as compared with those patients receiving any type of preoperative intervention in the hemostaseological system (the majority of the patients), no difference was observed regarding intraoperative parameters (duration of extracorporeal circulation and of the operation) and postoperative results (neurological, renal complications, myocardial infarction, psychiatric disturbances, etc.) when abciximab patients were compared with the reference populations. No patient of the abciximab group died within 30 days or during the 6 month follow-up period. The data show that coronary artery bypass grafting can be performed with similar results in abciximab-pretreated patients as in patients with other types of preoperative anticoagulation. Only slight modifications of the surgical management are recommended. As indicated by similar use IMA-grafts the quality of surgical treatment was not reduced.


Systematic Review of the Growth Rates and Influencing Factors in Thoracic Aortic Aneurysms.
The growth rates of thoracic aortic aneurysms (TAAs) and factors influencing their expansion are poorly understood. This study aimed to review systematically published literature describing TAA expansion and examine factors that may be associated with this. A comprehensive search of MEDLINE and Embase databases was performed until 30 April 2015. Studies describing rates of TAA growth were identified and systematically reviewed. Outcomes of interest were TAA growth rates and associated factors. Study quality was assessed using Scottish Intercollegiate Guidelines Network quality checklists for cohort studies. Eleven publications, involving 1383 patients, met the eligibility criteria and were included in the review. Included studies were generally low in quality. Aneurysm measurement and growth-rate estimation techniques were inconsistently reported. Mean growth rates for all TAAs ranged from 0.2 to 4.2 mm/year. Mean growth rates for ascending and aortic arch aneurysms ranged from 0.2 to 2.8 mm/year, while those for descending and thoracoabdominal aneurysms ranged from 1.9 to 3.4 mm/year in studies reporting according to anatomical location. Large aneurysm size, distal aneurysm locations, presence of Marfan's syndrome, and bicuspid aortic valve were consistently associated with accelerated TAA growth. Presence of chronic dissection and chronic obstructive pulmonary disorder were also implicated as risk factors for faster TAA growth. Associations between medical comorbidity and aneurysm expansion were conflicting. Previous aortic surgery and anticoagulants were reported to have a protective effect on aneurysm growth in two studies. There is a shortfall in the understanding of TAA expansion rates. Existing studies are heterogeneous in methodology and reported outcomes. Identified unifying themes suggest that TAAs grow at a slow rate with large presenting diameter, distal aneurysm, and history of bicuspid aortic valve or Marfan's syndrome serving as main risk factors for accelerated aneurysm growth. High-quality studies with a standardised approach to TAA growth assessment are required.


[Relationship between bacterial biofilm and chronic rhinosinusitis: a systematic review].
To evaluate the relationship between bacterial biofilm (BBF) and chronic rhinosinusitis (CRS). The database on line was searched to collect the studies on BBF and CRS. The method of meta analysis was used to analyze the data of suitable studies. Fourteen studies were included. System evaluation indicated that the BBF detection rate in CRS group was significantly higher than that in the control group (OR = 17.01, P < 0.01), and the nasal surgery's rate of BBF positive group was significantly higher than the negative group (OR = 3.99, P < 0.01). Preoperative Lund-Kennedy endoscopic score, Lund-MacKay CT score, symptom severity score, postoperative Lund-Kennedy score after six months showed no difference between BBF positive group and negative group. The presence of BBF is related to the pathogenesis of CRS and the history of nasal surgery.


Adsorption Behavior of Polycyclic Aromatic Hydrocarbons on Zn-Based Coordination Cluster Zn5: Competition, Synergy, and Mechanism.
In this work, adsorption behaviors of pyrene (PYR), fluoranthene (FLT), phenanthrene (PHE), and fluorene (FLU) on the coordination cluster [Zn5(H2Ln)6](NO3)4]·8H2O·2CH3OH (Zn5) were studied. The adsorption mechanism and spectrum analyses revealed that the synergistic effect of hydrophobic interaction, π-π stacking, and N-H···π interaction played a crucial role during the adsorption process. The maximum adsorption capacities of PYR, FLT, PHE, and FLU were 406.4, 399.7, 153.7, and 114.3 mg g-1, respectively, resulting from the Langmuir isotherm model. Quick removal of PYR and FLT was found in kinetic experiments with the adsorption equilibrium being reached within 1 min. Competitive adsorption indicated that the adsorption sites for PYR, FLT, PHE, and FLU on Zn5 were identical, and synergistic effects also existed in the adsorption process. Therefore, Zn5 has the potential to be used as an adsorbent in the field of wastewater treatment.


Neuronal decision-making circuits.
Studying the neural basis of decision-making has largely taken one of two paths: one has involved cell-by-cell characterization of neuronal circuits in invertebrates; and the other, single-unit studies of monkeys performing cognitive tasks. Here I shall attempt to bring these two disparate approaches together.


Plasticity and Clonality of Cancer Cell States.
While intratumoral heterogeneity has been extensively studied in terms of genetic alterations and phenotypic properties such as drug resistance, only recently has single-cell RNA-seq begun to expose the remarkable transcriptional diversity within tumors. A recent study of glioblastoma by Neftel et al. supports the emerging notion of cancer cell states and demonstrates their plasticity.


Surgical Complexity and Complications: The Need for a Common Language.
Quality measurement and outcome assessment have recently caught an attention of the neurosurgical community, but lack of standardized definitions and methodology significantly complicates these tasks. To identify a uniform definition of neurosurgical complications, to classify them according to etiology, and to evaluate them comprehensively in cases of intracranial tumor removal in order to establish a new, easy, and practical grading system capable of predicting the risk of postoperative clinical worsening of the patient condition. A retrospective analysis was conducted on all elective surgeries directed at removal of intracranial tumor in the authors' institution during 2-year study period. All sociodemographic, clinical, and surgical factors were extracted from prospectively compiled comprehensive patient registry. Data on all complications, defined as any deviation from the ideal postoperative course occurring within 30 days of the procedure, were collected with consideration of the required treatment and etiology. A logistic regression model was created for identification of independent factors associated with worsening of the Karnofsky Performance Scale (KPS) score at discharge after surgery in comparison with preoperative period. For each identified statistically significant independent predictor of the postoperative worsening, corresponding score was defined, and grading system, subsequently named Milan Complexity Scale (MCS), was formed. Overall, 746 cases of surgeries for removal of intracranial tumor were analyzed. Postoperative complications of any kind were observed in 311 patients (41.7%). In 223 cases (29.9%), worsening of the KPS score at the time of discharge in comparison with preoperative period was noted. It was independently associated with 5 predictive factors-major brain vessel manipulation, surgery in the posterior fossa, cranial nerve manipulation, surgery in the eloquent area, tumor size >4 cm-which comprised MCS with a range of the total score from 0 to 8 (higher score indicates more complex clinical situations). Patients who demonstrated KPS worsening after surgery had significantly higher total MCS scores in comparison with individuals whose clinical status at discharge was improved or unchanged (3.24 ± 1.55 versus 1.47 ± 1.58; P < 0.001). It is reasonable to define neurosurgical complication as any deviation from the ideal postoperative course occurring within 30 days of the procedure. Suggested MCS allows for standardized assessment of surgical complexity before intervention and for estimating the risk of clinical worsening after removal of intracranial tumor. Collection of data on surgical complexity, occurrence of complications, and postoperative outcomes, using standardized prospectively maintained comprehensive patient registries seems very important for quality measurement and should be attained in all neurosurgical centers.


Preparation of alpha-keto ester enol acetates as potential prodrugs of human neutrophil elastase inhibitors.
Enol acetates of a-keto esters with E configuration were prepared as potential prodrugs for human neutrophil elastase (HNE) inhibitors.


Postpartum intrauterine device insertion and postpartum tubal sterilization in the United States.
The purpose of this study was to estimate US rates of postpartum intrauterine device (IUD) insertion and postpartum tubal sterilization. Data from the 2001-2008 Nationwide Inpatient Sample were used to identify delivery hospitalizations with IUD insertion or tubal sterilization procedure codes. Estimated rates of postpartum IUD insertion and postpartum tubal sterilization were 0.27 and 770.67 per 10,000 deliveries, respectively. Although the rate of IUD insertion was similar across age groups, the rate of tubal sterilization increased with age. Nonetheless, 15% of tubal sterilizations occurred among women who were ≤ 24 years old. IUD insertion was more likely among women who delivered at teaching hospitals (odds ratio, 3.02; 95% confidence interval, 1.43-6.37); tubal sterilization was more likely among women without private insurance (odds ratio, 2.04; 95% confidence interval, 1.97-2.11). Among US postpartum women, IUD insertion occurs considerably less frequently than tubal sterilization, even among younger women for whom poststerilization regret is a concern.


Small cell carcinoma of epididymis: multimodal therapy.
Extrapulmonary small cell carcinoma is an infrequent tumor that can occur in various organs. Although a few sporadic reports about extrapulmonary small cell carcinoma have been published, much remains to be uncovered about the clinical features, optimal treatment, and natural history. We present a case of small cell carcinoma of the epididymis with retroperitoneal recurrence, an exceedingly rare tumor with behavior and treatment not well characterized. Multimodal therapy with chemotherapy and retroperitoneal lymph node dissection was necessary to manage this aggressive disease.


The effects of physical and semantic incongruities on auditory event-related potentials.
Twenty subjects listened to a series of simple sentences, spoken by a male voice, in which the last word was on occasions either made semantically incongruous or was unexpectedly spoken by a female voice. Averages of ERPs to the last words revealed that a consistent late negative component (N456) was associated with semantic incongruity and a late positive component (P416) with physical (voice) incongruity. The results were consistent with those in the visual modality by Kutas and Hillyard (1980a,b) and are interpreted in terms of the facilitatory and inhibitory effects of contextual priming on the processing of the words concerned. In a subsidiary experiment 6 subjects were required to repeat the last words of the same set of sentences as rapidly as possible. Verbal response latency increased by 62 msec to physically incongruous words and by 185 msec to semantically incongruous words.


Oxidative stress in schoolchildren with allergic rhinitis: propensity score matching case-control study.
Oxidative stress is defined as an imbalance between the level of reactive oxygen species and antioxidant mechanisms. Compared with asthma, the role of oxidative stress in allergic rhinitis (AR) has received little attention. To investigate the association between overall systemic oxidative stress and AR. We used a propensity score matching case-control study and selected 90 children who had experienced AR in the previous year. This AR group was then matched with 90 healthy children who comprised the control group. Propensity score matching, a statistical matching technique that accounts for the conditional probability of receiving an exposure given a vector of measured covariates, is used to reduce selection bias and potential confounders in observational study. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels were determined using a commercially available assay kit. Medical records and personal information were also reviewed. No statistically significant differences were found between patients with regard to age, sex, height, weight, educational level of parent, monthly household income, or distance of home from a main road. The mean TAS and TOS levels in the patient group were significantly higher than those of the control group (P = .03 and .048, respectively). The oxidative stress index, which is defined as the ratio of TOS to TAS, also increased in the AR group with statistical propensity (P = .08). In a multivariate logistic analysis, only TAS and TOS levels were significantly associated with increased risk of allergic rhinitis. Patients with AR have systemically elevated oxidative stress and systemically elevated TAS levels.


Controlled nucleation of lipid nanoparticles.
We describe a nucleation-based method which allows for the generation of monodisperse lipid nanoparticles over a range of diameters. Using a set of novel zwitterionic lipids and inverse phosphocholine lipids with pKas ranging from 2 to 5, we showed how the hydrodynamic diameter of lipid nanoparticles can be systematically manipulated over a 60 nm to 500 nm size range. Lipid nanoparticles were prepared by adding an anti-solvent, such as water, to the organic phase containing the lipid components. This led to super-saturation and the spontaneous formation of particles. The growth and final particle size was controlled by the ratio of the components in the ternary system: lipid, organic solvent and aqueous phase. Particles with diameter below 125 nm were formed under conditions where the super-saturation coefficient was between 2.3 and 20. PEG-lipid served as an efficient growth inhibitor except at very high and low lipid concentrations. Encapsulation efficiency of siRNA into lipid nanoparticles was shown to be pH-dependent and requires the protonation of the anionic carboxylate groups of the zwitterionic lipids, emphasizing the importance of electrostatic forces. This process enables high encapsulation efficiency of nucleic acids and allows the size of lipid nanoparticles to be controlled.


Exploiting desktop supercomputing for three-dimensional electron microscopy reconstructions using ART with blobs.
Three-dimensional electron microscopy allows direct visualization of biological macromolecules close to their native state. The high impact of this technique in the structural biology field is highly correlated with the development of new image processing algorithms. In order to achieve subnanometer resolution, the size and number of images involved in a three-dimensional reconstruction increase and so do computer requirements. New chips integrating multiple processors are hitting the market at a reduced cost. This high-integration, low-cost trend has just begun and is expected to bring real supercomputers to our laboratory desktops in the coming years. This paper proposes a parallel implementation of a computation-intensive algorithm for three-dimensional reconstruction, ART, that takes advantage of the computational power in modern multicore platforms. ART is a sophisticated iterative reconstruction algorithm that has turned out to be well suited for the conditions found in three-dimensional electron microscopy. In view of the performance obtained in this work, these modern platforms are expected to play an important role to face the future challenges in three-dimensional electron microscopy.


Effectiveness of measles vaccination for control of exposed children.
The effectiveness of measles vaccine for postexposure prophylaxis at educational centers was investigated. A total of 166 children who shared the classroom with 10 confirmed cases during the infectious period of cases were studied. Of total susceptible exposed children, 72% (54/75) were vaccinated and 25 contracted measles. Vaccine effectiveness in children vaccinated within 72 hours of exposure was 90.5% (95% confidence interval, 34%-99%).


Cutaneous T-cell lymphoma presenting as a rapidly enlarging ocular adnexal tumor.
A 63-year-old man, in good health previously, developed swelling and erythema of the right upper eyelid which progressed to involve both eyelids and surrounding tissues. After one month, he had a 9.0 x 9.0 x 3.5 cm mass despite two attempts at incisional drainage and treatment with antibiotics. Multiple asymptomatic erythematosus nodules (2-3 cm in diameter) developed on his back, trunk, and arms four weeks after onset of the eyelid erythema and swelling. Biopsies of two upper back papules and the eyelid disclosed cutaneous T-cell lymphoma, a lymphoproliferative malignancy of thymus derived lymphocytes originating in the skin. Systemic chemotherapy resulted in a marked decrease in the ocular adnexal mass but lymphomatous meningitis and quadriplegia developed. The patient died four months later; an autopsy was not performed. This case demonstrates that cutaneous T-cell lymphoma may rarely have its initial manifestation as a rapidly enlarging eyelid tumor.


Single-pulse terahertz spectroscopy monitoring sub-millisecond time dynamics at a rate of 50 kHz.
Slow motion movies allow us to see intricate details of the mechanical dynamics of complex phenomena. If the images in each frame are replaced by terahertz (THz) waves, such movies can monitor low-energy resonances and reveal fast structural or chemical transitions. Here, we combine THz spectroscopy as a non-invasive optical probe with a real-time monitoring technique to demonstrate the ability to resolve non-reproducible phenomena at 50k frames per second, extracting each of the generated THz waveforms every 20 μs. The concept, based on a photonic time-stretch technique to achieve unprecedented data acquisition speeds, is demonstrated by monitoring sub-millisecond dynamics of hot carriers injected in silicon by successive resonant pulses as a saturation density is established. Our experimental configuration will play a crucial role in revealing fast irreversible physical and chemical processes at THz frequencies with microsecond resolution to enable new applications in fundamental research as well as in industry.


Routes of putative afferent axons in rat lumbosacral ventral roots and pia mater.
Unmyelinated sensory axons occur in mammalian ventral roots. On this basis the law of Magendie has been questioned. With few exceptions, the current ideas on the routes that these axons might follow have been based on electron microscopic examination of transverse sections, and evidence obtained through electrophysiological experiments or tracer studies. The purpose of the present study is to examine putative afferent rat ventral root axons, which have been visualized directly by immunohistochemical labelling. After immunolabelling of axons containing substance P or calcitonin gene-related peptide in longitudinal sections from the ventral roots L4-S1, and in wholemount pia mater-rootlet preparations, fluorescent fibres were searched for in the microscope. The results show that some immunolabelled axons end blindly in the root, while others shift to the pia mater, or make U-turns. Some axons make irregular 'zigzag' deviations or branch. No immunoreactive axons were seen entering the spinal cord via the ventral roots. These observations support the view that the law of Magendie is valid.


An update on continuous-wave cyclophotocoagulation (CW-CPC) and micropulse transscleral laser treatment (MP-TLT) for adult and paediatric refractory glaucoma.
Continuous-wave cyclophotocoagulation (CW-CPC) is often preferred to medical and surgical treatments for managing refractory glaucoma. This review summarizes diode CW-CPC indications, history, histopathology, methods, efficacy and safety. It also provides an overview of the latest data available on micropulse transscleral laser treatment (MP-TLT) that uses repetitive micropulses of diode laser energy in an off-and-on cyclical fashion. A literature review was conducted on transscleral CW-CPC (CW-TSCPC), endoscopic CPC (ECP) and MP-TLT. Relevant series of adult and paediatric patients were included for assessing the procedures. Regarding CW-TCPC, highly variable success rates are reported in the literature, depending on the definition of success, type of underlying glaucoma, energy settings, follow-up duration and retreatment rates. CW-CPC often needs to be repeated, especially in paediatric patients. CW-CPC exposes to risks of inflammation and chronic ocular hypotony or phthisis with irreversible visual loss. CW-TSCPC has mainly been used in very severe forms of glaucoma, in painful eyes with limited visual potential or after filtering surgery failure. Published data on ECP are more limited but overall good success rates have been reported. Through the direct visualization of the targeted ciliary body in anatomically abnormal eyes, ECP is the preferred surgical procedure in paediatric refractory glaucoma. Complication rates are relatively low after ECP; however, large studies with long-term follow-up are needed. ECP may be used in difficult, refractory cases, but it is often used earlier when combined with cataract surgery. Despite limited data on the exact mechanism of action of MP-TLT and a lack of standardization of laser settings, the first data from heterogeneous case series shows that it has a similar efficacy and a better safety profile compared to CW-TSCPC in the medium term. Although they may lead to sight-threatening complications, both CW-TSCPC and ECP seem effective. ECP appears to be superior to CW-TSCPC in paediatric refractory glaucoma. Unlike ECP combined with cataract surgery, evidence supporting a wider use of CW-TSCPC and MP-TLT in earlier stages of neuropathy is lacking. While it now appears that the safety profile of MP-TLT is superior to that of CW-CPC, robust prospective comparative studies including homogeneous and well-defined cohorts of patients are still needed to confirm an at least comparable efficacy in the long term.


The role of viral glycoproteins in mumps virus-mediated antibody-dependent cellular cytotoxity in vitro.
Treatment of human peripheral blood lymphocytes with live or UV-inactivated mumps virions enhances antibody-mediated cellular cytotoxicity (ADCC), reflected by increased target cell lysis in a 51Cr-release assay or an increased number of plaque-forming cells on monolayers of bovine erythrocytes (Eb) in the presence of anti-Eb antibodies. Virus treatment of the Eb targets causes a similar enhancement. The role of viral glycoproteins in ADCC enhancement was investigated by using a panel of monoclonal antibodies raised in mice against mumps virions. Most of the lymphocytes bound mumps virions, as ascertained by indirect immunofluorescence. A high proportion of virus-treated lymphocytes also formed rosettes with Eb. Anti-HN antibodies inhibited rosetting to various degrees. Although antibodies with high haemagglutination inhibition titres were most efficient inhibitors, antibodies without this serological activity were also inhibitory. Anti-F antibodies were only weakly inhibitory, and anti-NP antibodies had no effect. Anti-HN antibodies also abrogated target cell lysis in the 51Cr-release assay and effector cell recruitment in the ADCC plaque assay by inhibiting virus-mediated Eb-lymphocyte interactions both at the target cell and at the effector cell level. Anti-F or anti-NP antibodies were only weakly or not at all inhibitory. The results suggest that virus-mediated enhancement of ADCC is caused by the HN glycoprotein, primarily (although perhaps not exclusively) by its improvement of the effector cell-target cell contacts necessary for the efficient execution of target cell lysis.


[5-Isothiocyanato-1,8-naphthalenedicarbox-4-methylphenylimide, a new fluorescence reagent for compounds containing amino groups (author's transl)].
5-Isothiocyanato-1,3-dioxo-2-p-tolyl-2,3-dihydro-1H-benz[de]isoquinoline (= 5-isothio-cyanato-1,8-naphthalenedicarbox-4-methylphenylimide, compd.5) was synthesized from 1H,3H-naphtho(1,8-cd)pyran-1,3-dione (= 1,8-naphtha-lenedicarboxylic anhydride, compd.1) through nitration, condensation with p-toluidine, reduction with tin(II)-chloride yielding 5-amino-1,3-dioxo-2-p-tolyl-2,3-dihydro-1H-benz(de)isoquino-line (4) as intermediate, and condensation with thiophosgene. Compd. 5 can be used for qualitative and quantitative analyses of compounds containing amino groups.


Effects of blood sample volume on hematocrit in critically ill children and neonates.
There are no studies correlating the volume of blood taken from children and hematocrit (Hct) stability, relating those changes to duration of stay, severity of illness or weight. Earlier studies in neonates suggest that repeated sampling results in a drop in Hct. To characterize the changes in Hct in children of all ages admitted to intensive care over a 5-day period following routine blood volume sampling. We undertook an open prospective observational study. Eligible children were recruited sequentially and data recorded for 5 days following admission. The bedside nurse recorded the daily volume of blood samples taken and transfusions given. Daily Hct was noted from the routine full blood count. The relationship between changes in Hct and blood sample volume and transfusion requirement was studied. There were no differences in mean Hct on admission at end of the study (P = 0.69, n = 30) nor in the median blood volume sampled between transfused and nontransfused groups (7.5 ml.kg(-1) vs 7.9 ml.kg(-1), P = 0.88). The largest blood sample volumes were taken on admission and from the smallest patients. We have quantitated the change in Hct and size of blood volume taken for routine laboratory studies. We suggest that children can tolerate 0.25 ml.kg(-1).day(-1) blood sampling without a fall in Hct and sampling can be tailored to the individual child according to the admission Hct.


Long-term effects of fertilization on soil organic carbon changes in continuous corn of northeast China: RothC model simulations.
Soil organic C (SOC) content can increase by managing land use practices in which the rates of organic C input exceed those of organic C mineralization. Understanding the changes in SOC content of Black soils (mainly Typic Halpudoll) in northeast China is necessary for sustainable using of soil resources there. We used the RothC model to estimate SOC levels of Black soils under monoculture cropping corn in a long-term fertilization trial at Gongzhuling, Jilin Province, China. The model outputs for the changes in SOC were compared with measured data in this long-term fertilization/manure trial. The sound performance of model in simulating SOC changes suggests that RothC is feasible with Black soils in the temperate climatic region of northeast China. The modeled and measured results indicated that the treatment without fertilizer/farmyard manure (FYM) addition led to a continuous decline in SOC during the study period and N and NPK fertilization were inadequate to maintain the SOC levels in the plow layer (upper 20 cm) unless FYM was added under the current conventional management associated with no above-ground crop residues returning into the soil. Soil organic carbon could follow the same path of decline if the same management practices are maintained. Model results indicate that returning above-ground crop residues to the soil from 2002 to 2022 would increase SOC by 26% for the treatment without fertilization addition, 40% for N treatment, 45% for NPK treatment, and 38% and 46% for N and NPK treatments with FYM addition, compared to the levels in the corresponding treatments in 2002. The simulation results suggest that the RothC model is a feasible tool to assess SOC trend under different management practices, and returning above-ground crop residues into the soil would lead to a remarkable increase in SOC of Black soils in the region.


Biliary Fasciola gigantica infestation in a nonendemic area--An intraoperative surprise.
A 7year old girl infected with the zoonotic trematode, Fasciola gigantica is reported because of the extreme rarity of this condition in our region. Because of the overlap in symptomatology and radiological features, the more common amebic/pyogenic liver abscess in the initial hepatic migratory phase and later choledochal cyst/biliary ascariasis when the parasite was finally located in the extrahepatic bile ducts, were thought of delaying effective treatment. The diagnosis was confirmed only by surgical exploration. The characteristic contrast enhanced computed tomography scan features retrospectively identified were multiple clustered hypodense lesions in the liver with peripheral enhancement in the acute hepatic migratory phase, and periportal tracking in the previously affected areas of the liver with biliary dilatation and a linear hypointense lesion within the common bile duct in the chronic phase. Although a known association, she did not have eosinophilia. This child, who became symptomatic at the age of 5.5years, also appears to be one of the youngest patients reported with Fasciola gigantica.


A novel luminol chemiluminescent method catalyzed by silver/gold alloy nanoparticles for determination of anticancer drug flutamide.
It was found that silver/gold alloy nanoparticles enhance the chemiluminescence (CL) of the luminol-H2O2 system in alkaline solution. The studies of UV-Vis spectra, CL spectra, effects of concentrations luminol, hydrogen peroxide and silver/gold alloy nanoparticles solutions were carried out to explore the CL enhancement mechanism. Flutamide was found to quench the CL signals of the luminol-H2O2 reaction catalyzed by silver/gold alloy nanoparticles, which made it applicable for the determination of flutamide. Under the optimum conditions, the CL intensity is proportional to the concentration of the flutamide in solution over the range 5.0 × 10(-7) to 1.0 × 10(-4)mol L(-1). Detection limit was obtained 1.2 × 10(-8)mol L(-1)and the relative standard deviation (RSD) γ5%. This work is introduced as a new method for the determination of flutamide in commercial tablets. Box-Behnken experimental design is applied to investigate and validate the CL measurement parameters.


Altered cytokine expression and sustained hypothermia following traumatic brain injury in heat acclimated mice.
Long-term exposure to moderate ambient heat (heat acclimation, HA, 30 days at 34+/-1 degrees C) provides protection toward a variety of stressors including traumatic brain injury. As previous studies suggested an anti-inflammatory effect of HA and given the ability of augmented pre-injury anti-inflammatory cytokine expression to harbor neuroprotection and to attenuate early post-injury expression of pro-inflammatory mediators, we hypothesized that HA-induced neuroprotection may involve enhanced pre-injury expression of anti-inflammatory mediators or a reduction in post-injury TNF alpha (TNFalpha) expression. Since the attenuation of inflammatory-associated entities has also been linked to mild hypothermia, an established neuroprotective paradigm, the effect of HA on post-injury body temperature was also studied. HA mice and normothermic (NT) counterparts were examined using a closed head injury model. Cytokines were measured within the ipsilateral cortex. Pre-injury protein levels of anti-inflammatory interleukins 10 and 4 (IL-10, IL-4) were quantified by enzyme-linked immunosorbent assays (ELISA). mRNA and protein levels of TNFalpha were quantified during the initial 2 h post-injury using semi-quantitative and real-time polymerase chain reaction (sqRT-PCR and qRT-PCR) or ELISA, respectively. Rectal temperatures were measured. HA induced augmented pre-injury IL-10 expression and a post-injury reduction in TNFalpha mRNA levels, as well as altered expression dynamics of TNFalpha protein. TNFalpha protein levels decreased relative to the sham state in HA mice only. HA mice displayed sustained post-injury hypothermia, namely significantly lower body temperature at 4 h post-injury. Given the evidence on the neuroprotective nature of hypothermia and anti-inflammatory cytokines, we suggest that these changes may contribute to HA-induced neuroprotection.


Holmium laser enucleation of the prostate for benign prostatic hyperplasia: effectiveness, safety, and overcoming of the learning curve.
To examine the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) for the surgical treatment of benign prostatic hyperplasia and to estimate the time to overcome the learning curve. From May 2008 to October 2009, 164 consecutive patients treated with HoLEP were enrolled in this study. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and postvoid residual urine (PVR) were documented preoperatively and at 6 weeks and 3, 6, 12, and 18 months postoperatively. The 164 study subjects were divided into 3 groups (group 1 the first 50 patients treated, group 2 the second 50, and group 3 the third 64), and perioperative data and complications were analyzed in these groups to determine the learning curve. In addition, the inverse and upward techniques were compared in terms of the effects and the stability of morcellation. The mean patient age was 69 years, and the average operation time was 62 minutes (range, 20-208 minutes). Mean prostate volume was 54.2 ml and mean resected tissue weight was 18.6 g. Postoperatively, IPSS and PVR decreased and Qmax increased significantly. Postoperative complications were transient incontinence (8.5%), urinary retention (4.3%), hematuria (3.0%), urinary tract infection (1.2%), and urethral stricture (0.6%), and intraoperative complications were minor capsular perforation (4%) and bladder injury (8%). HoLEP was found to be effective and safe regardless of prostate size. We recommend that a systematic educational program be established to reduce the learning curve.


Enhancing eating disorder recovery: Weight control beliefs predict body dissatisfaction in group cognitive behavioural therapy for body image.
Body dissatisfaction is one of the strongest predictors of eating disorder relapse. Yet, a dearth of research exists on factors that facilitate change in body dissatisfaction following treatment focused on symptom interruption. Recent research points to the role of weight control beliefs in predicting outcomes in patients with eating disorders. The primary objective of this research was therefore twofold: 1) To investigate the impact of group cognitive behavioural therapy (GCBT) on weight control beliefs and body dissatisfaction and 2) to examine the influence of weight control beliefs on body dissatisfaction over time. Participants were 50 adults with a recent eating disorder diagnosis who completed 10 sessions of GCBT for body image following GCBT for eating disorders. All participants completed the Eating Disorder Inventory and Weight Control Beliefs Questionnaire at baseline and post-treatment. Body dissatisfaction and weight control beliefs improved from pre- to post-treatment. Hierarchical linear regression analyses revealed that increases in lifestyle control beliefs, a subtype of weight control beliefs, predicted decreases in body dissatisfaction. Results underscore the utility of fostering healthy weight control beliefs to cultivate a positive body image in patients navigating the eating disorder recovery process.


Insulin binding to circulating monocytes in children with insulin-dependent and non-insulin-dependent diabetes mellitus.
This study describes insulin binding to circulating monocytes in 24 children with insulin-dependent diabetes mellitus (IDDM), five children with non-insulin-dependent diabetes mellitus (NIDDM), and 10 healthy and 12 obese control children. Insulin binding to monocytes was greatly increased in untreated IDDM children with obvious ketoacidosis (5.51 +/- 3.49 vs. 1.91 +/- 0.47 pg/10(6) cells, P less than 0.01), whereas it was decreased in those without obvious ketoacidosis (1.39 +/- 0.30 vs. 1.91 +/- 0.47 pg/10(6) cells, P less than 0.01). Insulin treatment restored insulin binding almost to the level of control children in both ketoacidotic and non-ketoacidotic patients. Insulin binding to monocytes was markedly decreased in untreated NIDDM children with hyperinsulinemia compared with healthy control children (0.73 +/- 0.27 vs. 1.91 +/- 0.47 pg/10(6) cells, P less than 0.01) or obese control children (0.73 +/- 0.27 vs. 1.33 +/- 0.35 pg/10(6) cells, P less than 0.01). These data indicate that changes in insulin secretion and metabolic conditions might be involved in the fluctuation of the number of insulin receptors in IDDM children as well as in NIDDM children.


Arrest of descent in second stage of labour secondary to macrosomia: a case report.
Fetal macrosomia, defined as birth weight greater than 4000 g, complicates 10% of pregnancies and is a well-documented cause of prolonged second stage of labour, as well as of arrest of descent of the fetal presenting part. A multigravida woman with gestational diabetes mellitus was admitted in labour at term, and progressed to full dilatation. The fetal vertex failed to descend beyond -3 station. An emergency Caesarean section was performed and a 6452 g male infant was delivered. Physicians should be aware of the possibility of macrosomia as the cause of failure of descent in the second stage. A heightened state of suspicion should be maintained, particularly in a multigravida woman with a prior macrosomic baby and the presence of other predisposing factors such as gestational diabetes mellitus.


Hexavalent vaccines in preterm infants: an update by Italian Society of Pediatric Allergy and Immunology jointly with the Italian Society of Neonatology.
Hexavalent vaccines, protecting against six diseases (diphtheria, tetanus, pertussis [DTaP], poliovirus, hepatitis B virus [HBV], and Haemophilus influenzae type b [Hib], are routinely the standard of care in Europe. The use of combined vaccines allows the reduction of number of injections and side effects, the reduction of costs, and the increase in adherence of the family to the vaccination schedule both in terms of the number of doses and timing. The safety profile, efficacy and effectiveness of hexavalent vaccines have been extensively documented in infants and children born at term, and data are accumulating in preterm infants. Hexavalent vaccines are particularly important for preterm infants, who are at increased risk for severe forms of vaccine preventable diseases. However, immunization delay has been commonly reported in this age group. All the three hexavalent vaccines currently marketed in Italy can be used in preterm infants, and recent data confirm that hexavalent vaccines have a similar or lower incidence of adverse events in preterm compared to full-term infants; this is likely due to a weaker immune system response and reduced ability to induce an inflammatory response in preterm infants. Apnoea episodes are the adverse events that can occur in the most severe preterm infants and / or with history of respiratory distress. The risk of apnoea after vaccination seems to be related to a lower gestational age and a lower birth weight, supporting the hypothesis that it represents an unspecific response of the preterm infant to different procedures. High seroprotection rates have been reported in preterm infants vaccinated with hexavalent vaccine. However, a lower gestational age seems to be associated with lower antibody titres against some vaccine antigens (e.g. HBV, Hib, poliovirus serotype 1, and pertussis), regardless of the type of hexavalent vaccine used. Waiting for large effectiveness studies, hexavalent vaccines should be administered in preterm infants according to the same schedule recommended for infants born at term, considering their chronological age and providing an adequate monitoring for cardio-respiratory events in the 48-72 h after vaccination, especially for infants at risk of recurrence of apnoea.


Facile preparation of carbohydrate microarrays by site-specific, covalent immobilization of unmodified carbohydrates on hydrazide-coated glass slides.
[reaction: see text] A new, simple and efficient immobilization method to attach mono-, di-, oligo-, and polysaccharides to hydrazide-coated glass slides was developed. Protein and cell-binding experiments show that the carbohydrate microarrays prepared by this method are applicable for the rapid analysis of protein-carbohydrate interactions and fast detection of pathogens.


The Role of the Tyrosine-Based Sorting Signals of the ORF3a Protein of SARS-CoV-2 on Intracellular Trafficking, Autophagy, and Apoptosis.
The open reading frame 3a (ORF3a) is an accessory transmembrane protein that is important to the pathogenicity of SARS-CoV-2. The cytoplasmic domain of ORF3a has three canonical tyrosine-based sorting signals (YxxΦ; where x is any amino acid and Φ is a hydrophobic amino acid with a bulky -R group). They have been implicated in the trafficking of membrane proteins to the cell plasma membrane and to intracellular organelles. Previous studies have indicated that mutation of the 160YSNV163 motif abrogated plasma membrane expression and inhibited ORF3a-induced apoptosis. However, two additional canonical tyrosine-based sorting motifs (211YYQL213, 233YNKI236) exist in the cytoplasmic domain of ORF3a that have not been assessed. We removed all three potential tyrosine-based motifs and systematically restored them to assess the importance of each motif or combination of motifs that restored efficient trafficking to the cell surface and lysosomes. Our results indicate that the YxxΦ motif at position 160 was insufficient for the trafficking of ORF3a to the cell surface. Our studies also showed that ORF3a proteins with an intact YxxΦ at position 211 or at 160 and 211 were most important. We found that ORF3a cell surface expression correlated with the co-localization of ORF3a with LAMP-1 near the cell surface. These results suggest that YxxΦ motifs within the cytoplasmic domain may act cooperatively in ORF3a transport to the plasma membrane and endocytosis to lysosomes. Further, our results indicate that certain tyrosine mutants failed to activate caspase 3 and did not correlate with autophagy functions associated with this protein.


Application of the shsp gene, encoding a small heat shock protein, as a food-grade selection marker for lactic acid bacteria.
Plasmid pSt04 of Streptococcus thermophilus contains a gene encoding a protein with homology to small heat shock proteins (A. Geis, H. A. M. El Demerdash, and K. J. Heller, Plasmid 50:53-69, 2003). Strains cured from the shsp plasmids showed significantly reduced heat and acid resistance and a lower maximal growth temperature. Transformation of the cloned shsp gene into S. thermophilus St11 lacking a plasmid encoding shsp resulted in increased resistance to incubation at 60 degrees C or pH 3.5 and in the ability to grow at 52 degrees C. A food-grade cloning system for S. thermophilus, based on the plasmid-encoded shsp gene as a selection marker, was developed. This approach allowed selection after transfer of native and recombinant shsp plasmids into different S. thermophilus and Lactococcus lactis strains. Using a recombinant plasmid carrying an erythromycin resistance (Em(r)) gene in addition to shsp, we demonstrated that both markers are equally efficient in selecting for plasmid-bearing cells. The average transformation rates in S. thermophilus (when we were selecting for heat resistance) were determined to be 2.4 x 10(4) and 1.0 x 10(4) CFU/0.5 micro g of DNA, with standard deviations of 0.54 x 10(4) and 0.32 x 10(4), for shsp and Em(r) selection, respectively. When we selected for pH resistance, the average transformation rates were determined to be 2.25 x 10(4) and 3.8 x 10(3) CFU/0.5 micro g of DNA, with standard deviations of 0.63 x 10(4) and 3.48 x 10(3), for shsp and Em(r) selection, respectively. The applicability of shsp as a selection marker was further demonstrated by constructing S. thermophilus plasmid pHRM1 carrying the shsp gene as a selection marker and the restriction-modification genes of another S. thermophilus plasmid as a functional trait.


D-1553: A novel KRASG12C inhibitor with potent and selective cellular and in vivo antitumor activity.
D-1553 is a small molecule inhibitor selectively targeting KRASG12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D-1553. Potency and specificity of D-1553 in inhibiting GDP-bound KRASG12C mutation were determined by thermal shift assay and KRASG12C -coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D-1553 alone or in combination with other therapies were evaluated in KRASG12C mutated cancer cells and xenograft models. D-1553 showed selective and potent activity against mutated GDP-bound KRASG12C protein. D-1553 selectively inhibited ERK phosphorylation in NCI-H358 cells harboring KRASG12C mutation. Compared to the KRAS WT and KRASG12D cell lines, D-1553 selectively inhibited cell viability in multiple KRASG12C cell lines, and the potency was slightly superior to sotorasib and adagrasib. In a panel of xenograft tumor models, D-1553, given orally, showed partial or complete tumor regression. The combination of D-1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D-1553 alone. These findings support the clinical evaluation of D-1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRASG12C mutation.


Older-adult marijuana users and ex-users: Comparisons of sociodemographic characteristics and mental and substance use disorders.
The increasing numbers of older-adult marijuana users call for better understanding of their mental and substance use disorders (MSUDs). Data came from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; N=14,715 respondents aged 50 +). Multinomial logistic regression analysis was used to compare never users, past-year users, and ex-users on past-year and lifetime MSUDs. Binary logistic regression analysis was used to examine the association of marijuana use patterns in the past year and during the peak use period with lifetime MSUDs. Of the 50+ age group, 3.9% were past-year marijuana users and 21.7% were ex-users. Past-year users did not differ from ex-users with respect to past-year or lifetime mental disorders, but they had higher risks of past-year other drug use (RRR=2.73, 95% CI=1.63-4.55), alcohol use (RRR=2.30, 95% CI=1.78-2.98), and tobacco/nicotine use (RRR=1.87, 95% CI=1.50-2.34) disorders. Among past-year users, the number of joints smoked during the peak use period (OR=1.14, 95% CI=1.04-1.26) and past-year use frequency (OR=2.20, 95% CI=1.37-3.52) were significantly associated with greater odds of lifetime marijuana/other drug use disorder. Among ex-users, the number of joints smoked during the peak use period was significantly associated with any mental (OR=1.05, 95% CI=1.01-1.09) and marijuana and/or other drug use (OR=1.13, 95% CI=1.06-1.21) disorder. Older-adult past-year marijuana users and ex-users had similarly high risks for past-year and lifetime mental disorders, but past-year users had a higher risk for substance use disorders. Health/mental health providers should be concerned about the increasing number of older-adult long-term marijuana users with MSUDs.


Immunochemistry of scorpion alpha-toxins: purification and characterization of two functionally independent IgG populations raised against toxin II of Androctonus australis Hector.
We report the isolation and characterization of two IgG populations specific to two synthetic peptides corresponding to two antigenic sites of toxin II of the North African scorpion Androctonus australis Hector. Firstly, thanks to the use of: (1) antigenic homology studies between toxin II of A. australis Hector and toxin III of Buthus occitanus tunetanus, (2) chemical modification of toxin II of A. australis Hector, and (3) prediction of the localization of the four major antigenic sites of scorpion alpha-toxins by the method developed by Hopp and Woods [Proc. natn. Acad. Sci. U.S.A. 78, 3824-3828 (1981)], we have established that the region around the disulfide bridge between cysteines 12 and 63 as well as the stretch of residues 50-59 probably each enclosed an antigenic site. Secondly, the synthetic replicates of these regions linked to Sepharose allowed us to isolate, by immunoaffinity chromatography, two IgG populations from the whole anti-toxin II of A. australis Hector IgGs. Finally, each of these two IgG populations was shown to be specific to one antigenic site as evidenced by the multideterminant effect on the slopes of binding curves developed by Berzofsky et al. [Biochemistry 15, 2113-2121 (1976)]. Furthermore, these two IgG populations were found to be functionally independent and this could be related to the fact that the two regions carrying the two antigenic sites are not close to each other in space and that there is neither steric hindrance nor cooperative effects between them. The association constant of these site-specific IgG populations was calculated and found to be equal to 1.18-5.14 X 10(9) l/mole for IgG anti-site 1 and 1.16-5.62 X 10(9) l/mole for IgG anti-site 2 respectively by Sips [J. chem. Phys. 16, 490-495 (1948)], Scatchard [Am. N.Y. Acad. Sci. 51, 660-772 (1949)] and Steward and Petty [Immunology 23, 881-887 (1972)] representations. The index of heterogeneity of 0.9 for anti-P1 and anti-P2 indicates the purification of essentially homogeneous affinity IgG populations.


[Establishment of leukaemia cell lines and their significance for clinical and experimental oncology (author's transl)].
Permanent in vitro growing leukemic cell lines have been established from all types of immunologically classified childhood leukemias. Essential characteristics of primary blasts and cultured cells are identical. In contrast to lymphoblastoid, non-leukemic cell lines, the Epstein-Barr-virus specific nuclear angiten (EBNA) is not detected. Up to now 8 Non-B-non-T cell lines (6 of them were derived from children with acute lymphoblastic leukemia, 2 from patients with chronic myeloid leukemia), 8 T-lines and one B-line have been established. Three Non-B-non-T lines from children with acute lymphoblastic leukemia (KM-3, RU-3, MH-3) and one T-cell line (JM) were cultivated by ourselves. Cultured blasts represent a pure tumor material which can be propagated in large quantities. Leukemic cell lines reveal a new approach for the search after leukemia-associated proteins and represent another possibility for the experimental investigation of the etiology of leukemia.


Application of Photoacoustic Imaging for Lymphedema Treatment.
Lymphatic vessels are difficult to identify using existing modalities as because of their small diameter and the transparency of the lymph fluid flowing through them. Here, we introduce photoacoustic lymphangiography (PAL), a new modality widely used for lymphedema treatment, to observe limb lymphatic vessels. The photoacoustic imaging system used in this study can simultaneously visualize lymphatic vessels and veins with a high resolution (0.2 mm) and can also observe their three-dimensional relationship with each other. High-resolution images of the lymphatic vessels, detailed structure of the dermal back flow, and the three-dimensional positional relationship between the lymphatic vessels and veins were observed by PAL. The clear image provided by PAL could have a major application in pre- and postoperative use during lymphaticovenular anastomosis for lymphedema treatment.


Precocious differentiation of chick embryo pancreas in vitro. Roles of prednisolone, insulin and L-thyroxine.
The hormonal requirement for functional differentiation of chick embryo pancreas were investigated by using organ cultures in chemically defined medium. The hormones tested were prednisolone, insulin and thyroxine, and the parameters examined were alpha-amylase (EC 188.8.131.52) and chymotrypsinogen (EC 126.96.36.199) activities, and the ultrastructure of the tissues. Addition of prednisolone alone to explants from 14-day-old chicken embryo pancreas for 3 days increased the activities of amylase and chymotrypsinogen in the tissues by 3.4- and 6.6-fold, respectively, those of tissues before cultivation. Neither thyroxine or insulin alone, nor both hormones together affected pancreatic exocrine differentiation. Thyroxine enhanced the effect of prednisolone on both enzymes, but insulin did not. When the explants were cultured in the medium containing all three hormones, maximum enzyme activities were observed; amylase or chymotrypsinogen activity being 7- or 18-fold, respectively, that of tissues before cultivation. But these three hormones were not simultaneously necessary. Morphological differentiation was also observed in explants cultuvated in medium containing these three hormones. These results suggest that glucocorticoids are essential for normal differentiation of chick pancreas during the late fetal period, possibly with insulin and thyroxine, and also support the idea that pancreatic enzymes are controlled separately.


Unplanned readmissions after primary total knee arthroplasty in Korean patients: Rate, causes, and risk factors.
Unplanned hospital readmissions are indicators of the quality and performance of a health care system, but data on early readmission after primary total knee arthroplasty (TKA) in the Asian population are limited. The purpose of this study was to determine the causes, risk factors, and rate of unplanned readmission after primary TKA at a single institution in Korea. We analyzed all primary TKAs from 2004 to 2013 using the data from our institutional electronic database. A total of 4596 TKAs were performed on 3049 patients. All unplanned readmissions within 30 and 90days of discharge were identified, categorized into arthroplasty-related, medical, and other orthopedic causes. The overall unplanned readmission rate was 1.9% (n=59) within 30days and 3.3% (n=101) within 90days, and both the 30 and 90day readmission rates remained stable over the entire study period. The majority of readmissions involved arthroplasty-related causes; the most common cause being wound problems, accounting for 22% (13/59) within 30days and 24% (24/101) within 90days. Age (P=0.029) and hypertension (P=0.021) were identified as risk factors for unplanned readmissions after TKA. This study demonstrates that unplanned readmissions after TKA are not infrequent in Korean patients and has identified wound complication as the most frequent cause of unplanned readmissions. Optimized care systems should be established to minimize unplanned readmissions, particularly for patients with high risk factors.


Cyclin-dependent kinases at the G1-S transition of the mammalian cell cycle.
In the mammalian cell cycle, the transition from the G1 phase to S phase, in which DNA replication occurs, is dependent on tight cell size control and has been shown to be regulated by the cyclin-dependent kinases (Cdks) 2, 3, 4 and 6. Activities of Cdks are controlled by association with cyclins and reversible phosphorylation reactions. An additional level of regulation is provided by inhibitors of Cdks. G1-S and S phase substrates of these enzymes include proteins implicated in replication and transcription. Whereas the regulation and role of Cdk2, 4 and 6 has intensively been studied, less is known about Cdk3. Recent data provide first insights into the regulation of Cdk3-associate kinase activity and suggest a model how Cdk3 participates in the regulation of the G1-S transition. Although it has been shown that these G1-Cdks are absolutely essential for a proper transition into S phase, their physiological activation is not sufficient to directly initiate replication independently of cell size. Evidence obtained from yeast and Xenopus indicate the initiation of DNA replication to be a two-step process: the origin recognition complex, Cdc6 and Mcm proteins are required for establishing the prereplicative complex and the activities of Cdks and of Cdc7 kinase then trigger the G1-S transition. Recent findings provide evidence that the overall mechanism of initiation of replication is conserved in mammalian cells.


Determination of the distribution constants of aromatic compounds and steroids in biphasic micellar phosphonium ionic liquid/aqueous buffer systems by capillary electrokinetic chromatography.
The distribution constants of some analytes, closely connected to the petrochemical industry, between an aqueous phase and a phosphonium ionic liquid phase, were determined by ionic liquid micellar electrokinetic chromatography (MEKC). The phosphonium ionic liquids studied were the water-soluble tributyl(tetradecyl)phosphonium with chloride or acetate as the counter ion. The retention factors were calculated and used for determination of the distribution constants. For calculating the retention factors the electrophoretic mobilities of the ionic liquids were required, thus, we adopted the iterative process, based on a homologous series of alkyl benzoates. Calculation of the distribution constants required information on the phase-ratio of the systems. For this the critical micelle concentrations (CMC) of the ionic liquids were needed. The CMCs were calculated using a method based on PeakMaster simulations, using the electrophoretic mobilities of system peaks. The resulting distribution constants for the neutral analytes between the ionic liquid and the aqueous (buffer) phase were compared with octanol-water partitioning coefficients. The results indicate that there are other factors affecting the distribution of analytes between phases, than just simple hydrophobic interactions.


Two oligostilbenes, cis- and trans-diptoindonesin B, from Dryobalanops oblongifolia.
Two oligostilbenes, cis- and trans-diptoindonesin B, have been isolated from the tree bark of Dryobalanops oblongifolia (Dipterocarpaceae). The structures and relative configurations of both compounds were determined on the basis of spectroscopic evidence, including 2D-NMR spectroscopic analysis.


Recurrent, life-threatening PE in the setting of popliteal vein aneurysm in pregnancy: a case report.
Popliteal vein aneurysms (PVA) are a rare clinical entity with unknown etiology that pose a significant risk for venous thromboembolic events (VTE). The current literature supports anticoagulation and operative management. There are few case reports of PVA in pregnancy. We present a unique case of a pregnant patient with recurrent pulmonary embolism (PE) in the setting of PVA with intra-aneurysmal thrombosis who ultimately underwent surgical excision. A previously healthy 34-year-old G2P1 at 30 weeks gestation presented to the emergency department with shortness of breath and chest pain. She was diagnosed with PE and subsequently required intensive care unit (ICU) admission and thrombolysis for a massive PE. While on a therapeutic dose of tinzaparin she had recurrence of PE in the post-partum period. She was treated with supratherapeutic tinzaparin and subsequently transitioned to warfarin. She was found to have a PVA and ultimately underwent successful PVA ligation. She remains on anticoagulation for secondary prevention of VTE. PVA are a rare but potentially fatal source of VTE. Patients most commonly present with symptoms of PE. The risk of VTE is elevated in the pro-thrombotic states of pregnancy and the post-partum period due to both physiologic and anatomical changes. The recommended management of PVA with PE is anticoagulation and surgical resection of the aneurysm, however this can be complicated in the setting of pregnancy. We demonstrated that pregnant patients with PVA can be temporized with medical management to avoid surgical intervention during pregnancy, but require close symptom monitoring and serial imaging to reassess the PVA, with high index of suspicion for recurrent VTE. Ultimately, patients with PVA and PE should undergo surgical resection to reduce the risk of recurrence and long-term complications. The ideal duration of post-operative anticoagulation remains unclear, and should likely be decided on based on risks, benefits, values, and shared decision making with the patient and their care provider.


[Retention and biomechanics of "retention complexes" 2. Retention complexes of Akers, Roach and Ney].
The authors describe the different "retentive complexes" proposed by the Akers, Roach and Ney schools and analyse their biomechanical validity.


Anatomical Variations of the Optic Nerve in the Sphenoid Sinus: Do Ethnic Variations Matter?
There are several variations in the anatomical relations of the optic nerve with the sphenoid sinus. Proper understanding of these variations is clinically important to minimize injuries associated with surgical procedures that involve the sphenoid sinus. CT scans of paranasal sinuses obtained prior to any endoscopic surgery in the sphenoid sinus area is useful for designing operative strategies. Ethnic variations in sinonasal anatomy have been documented. The objective was to study the pattern of relationship between optic nerve and the sphenoid sinus using computerized tomographic imaging in a north Indian population, to compare our findings with previous studies in different ethnic groups and find out if ethnic variations in such a relationship matter. A prospective study was conducted on 300 patients who underwent computed tomography of the paranasal sinuses from Sept 2020 to June 2021. Relationship of optic nerves to the sphenoid sinuses was categorized according to DeLano classification. Pneumatization of the anterior clinoid process and bony dehiscence of optic nerve was also observed. Type 1 position of optic nerve was seen in 69.3%, Type 2 in 20.9%, Type 3 in 3% and Type 4 in 6.8% of sinuses. The pneumatization of anterior clinoid process (ACP) was observed in 10.5% and the bony dehiscence of optic nerve was noted in 6.5% sinuses. Bony dehiscence of optic canal had associated ACP pneumatization in 64.1% sinuses.The variability of the relation of optic nerve to the sphenoid sinus even in the persons of same ethnicity precludes a definite role of ethnicity in these variations. Other factors possibly contributing to such a relationship have been discussed.


Collateral estimation by susceptibility-weighted imaging and prediction of functional outcomes after acute anterior circulation ischemic stroke.
To determine the value of susceptibility-weighted imaging (SWI) for collateral estimation and for predicting functional outcomes after acute ischemic stroke. To identify independent predictors of favorable functional outcomes, age, sex, risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline diffusion-weighted imaging (DWI) lesion volume, site of steno-occlusion, SWI collateral grade, mode of treatment, and successful reperfusion were evaluated by multiple logistic regression analyses. A total of 152 participants were evaluated. A younger age (adjusted odds ratio (aOR), 0.42; 95% confidence interval (CI) 0.34 to 0.77; P < 0.001), a lower baseline NIHSS score (aOR 0.90; 95% CI 0.82 to 0.98; P = 0.02), a smaller baseline DWI lesion volume (aOR 0.83; 95% CI 0.73 to 0.96; P = 0.01), an intermediate collateral grade (aOR 9.49; 95% CI 1.36 to 66.38; P = 0.02), a good collateral grade (aOR 6.22; 95% CI 1.16 to 33.24; P = 0.03), and successful reperfusion (aOR 5.84; 95% CI 2.08 to 16.42; P = 0.001) were independently associated with a favorable functional outcome. There was a linear association between the SWI collateral grades and functional outcome (P = 0.008). Collateral estimation using the prominent vessel sign on SWI is clinically reliable, as it has prognostic value.


Evidence for metabotropic excitatory amino acid receptor heterogeneity: developmental and brain regional studies.
To examine whether multiple subtypes of the excitatory amino acid (EAA) receptor coupled to phosphoinositide (PPI) hydrolysis exist, we have pharmacologically characterized the PPI response in neonatal and adult rat brain. Activation of PPI hydrolysis was determined by the accumulation of [3H]inositol monophosphate in brain slices prelabeled with [3H]inositol. In neonatal hippocampus, D,L-2-amino-3-phosphonopropionic acid (AP3; 1 mM) inhibited the cis-1-aminocyclopentane-1,3-dicarboxylic acid (IUPAC nomenclature; ACPD; 100 microM)- and quisqualate (Quis; 100 microM)-stimulated PPI hydrolysis by 73 and 66%, respectively, but had no effect in neonatal cerebellum. In adult hippocampus, AP3 stimulated PPI hydrolysis with potency and efficacy comparable to those of Quis and ACPD and completely masked the Quis concentration-response curve. In adult cerebellum, only Quis behaved as a full agonist on the PPI response. The Quis concentration-response curve was shifted rightward with a fourfold decrease in potency in the presence of ACPD (5 mM), whereas it was nearly additive with the PPI response induced by AP3 (5 mM). Thus, our data reveal significant developmental and brain regional differences in metabotropic EAA receptor responses and support the notion that this receptor is heterogeneous, in both a regionally specific and a developmentally dependent manner.


Associations Between Depressive Symptoms, Fear of Hypoglycemia, Adherence to Management Behaviors and Metabolic Control in Children and Adolescents with Type 1 Diabetes.
We examined the relationship between two malleable risk factors, depressive symptoms and fear of hypoglycemia, in children and adolescents with Type 1 diabetes and their relationship to two important outcomes, adherence behaviors and metabolic control. To assess this relationship, we used a multidimensional measure of adherence, assessing frequency of both blood glucose monitoring and healthy behaviors including diet and exercise. We predicted that higher levels of depressive symptoms and higher levels of fear of hypoglycemia would be associated with worse metabolic control as mediated by poor adherence. Eighty-three children and adolescents ages 8 to 20 (M = 13.87, SD 3.21) were recruited from March 2014 to October 2014 at an outpatient diabetes clinic in a moderately sized Southeastern city within the USA. Nested models were evaluated using structural equation modeling. Adherence significantly mediated the relationship between depressive symptoms and metabolic control with more depressive symptoms leading to worse metabolic control. Adherence marginally mediated the relationship between fear of hypoglycemia and metabolic control; however, less fear of hypoglycemia was associated with worse metabolic control. In a combined model, adherence continued to significantly mediate the relationship between depressive symptoms and metabolic control, while also independently significantly mediating the relationship between fear of hypoglycemia and metabolic control. This finding was also contrary to the predicted relationship with less fear of hypoglycemia leading to worse metabolic control. The results indicate that youth with fewer depressive symptoms and more fear of hypoglycemia had better adherence to their treatment regimen, which was associated with better metabolic control. The results of this study highlight the importance of screening for depression and fear of hypoglycemia during routine clinic visits to optimize adherence and metabolic control.


Visiting nature is associated with lower socioeconomic inequalities in well-being in Wales.
Natural environments can promote well-being through multiple mechanisms. Many studies have investigated relationships between residential green/blue space (GBS) and well-being, fewer explore relationships with actual use of GBS. We used a nationally representative survey, the National Survey for Wales, anonymously linked with spatial GBS data to investigate associations of well-being with both residential GBS and time in nature (N = 7631). Both residential GBS and time spent in nature were associated with subjective well-being. Higher green-ness was associated with lower well-being, counter to hypotheses (predicting the Warwick and Edinburgh Mental Well-Being Scale (WEMWBS): Enhanced vegetation index β = - 1.84, 95% confidence interval (CI) - 3.63, - 0.05) but time spent in nature was associated with higher well-being (four hours a week in nature vs. none β = 3.57, 95% CI 3.02, 4.13). There was no clear association between nearest GBS proximity and well-being. In support of the equigenesis theory, time spent in nature was associated with smaller socioeconomic inequalities in well-being. The difference in WEMWBS (possible range 14-70) between those who did and did not live in material deprivation was 7.7 points for those spending no time in nature, and less at 4.5 points for those spending time in nature up to 1 h per week. Facilitating access and making it easier for people to spend time in nature may be one way to reduce socioeconomic inequalities in well-being.


Mass-spectrometric studies of new 6-nitroquipazines-serotonin transporter inhibitors.
Six synthesized 6-nitroquipazine derivatives were examined by electron ionization (EI) and electrospray ionization (ESI) mass spectrometry in positive and negative ion mode. The compounds exhibit high affinity for the serotonin transporter (SERT) and belong to a new class of SERT inhibitors. The EI mass spectra registered in negative ion mode showed prominent molecular ions for all the compounds studied. All EI mass spectra and all ESI mass spectra showed similar fragmentation pathways of molecular ions, but the pathways differed between EI and ESI. The differences were explained with the aid of theoretical evaluation of the stability of the respective radical ions (EI MS) and protonated ions (ESI MS).


Molecular basis of a high Hb A2/Hb Fβ-thalassemia trait: a retrospective analysis, genotype-phenotype interaction, diagnostic implication, and identification of a novel interaction with α-globin gene triplication.
β 0-thalassemia deletion removing 5´β-globin promoter usually presents phenotype with high hemoglobin (Hb) A2 and Hb F levels. We report the molecular characteristics and phenotype-genotype correlation in a large cohort of the β 0-thalassemia with 3.4 kb deletion. A total of 148 subjects, including 127 heterozygotes, 20 Hb E-β-thalassemia patients, and a double heterozygote with α-globin gene triplication, were recruited. Hb and DNA analysis were performed to identify thalassemia mutations and four high Hb F single nucleotide polymorphisms (SNPs) including four base pair deletion (-AGCA) at A γ-globin promoter, rs5006884 on OR51B6 gene, -158 G γ-XmnI, BCL11A binding motifs (TGGTCA) between 3´A γ-globin gene and 5´δ-globin gene. It was found that heterozygous β 0-thalassemia and Hb E-β 0-thalassemia with 3.4 kb deletion had significantly higher Hb, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and Hb F values as compared with those with other mutations. Co-inheritance of heterozygous β 0-thalassemia with 3.4 kb deletion and α-thalassemia was associated with even higher MCV and MCH values. The Hb E-β 0-thalassemia patients carried a non-transfusion-dependent thalassemia phenotype with an average Hb of around 10 g/dL without blood transfusion. A hitherto undescribed double heterozygous β 0-thalassemia with 3.4 kb deletion and α-globin gene triplication presented as a plain β-thalassemia trait. Most of the subjects had wild-type sequences for the four high Hb F SNPs examined. No significant difference in Hb F was observed between those of subjects with and without these SNPs. Removal of the 5´β-globin promoter may likely be responsible for this unusual phenotype. The results indicate that β 0-thalassemia with 3.4 kb deletion is a mild β-thalassemia allele. This information should be provided at genetic counseling and prenatal thalassemia diagnosis.


Acetylcholinesterase fibers and the development of senile plaques.
A new, highly sensitive histochemical technique for actylcholinesterase (AChE) was applied to a study of Alzheimer's disease brain tissue. Many immature senile plaques were seen to be developing along AChE-positive axons in the hippocampus and neocortex. Single fibers often displayed multiple lesions, showing stages of initial swelling, ballooning with the appearance of AChE in the surrounding extra-axonal space, and development of an AChE-amyloid intense core accompanied by a weakly staining AChE-positive halo. Except for the core and halo, AChE-positive material was seldom detected in so-called mature plaques which are large and incorporate many degenerating neuritic elements surrounding an amyloid core. Lesion data in rats established the relationship between AChE-positive neocortical axons and medial basal forebrain cholinergic cells. In Alzheimer's disease tissue, many degenerating neurons in the basal forebrain were detected by the AChE histochemical stain, along with pathological alterations in the proximal axons en route to their cortical terminal fields. These data provide direct evidence of an association between the cholinergic system of the basal forebrain and the early formation of senile plaques in the cortex in Alzheimer's disease.


The immediate effect of whole body vibration training on the electromyographic activity of contralateral hand muscles; a randomized controlled trial.
Whole Body Vibration (WBV) has been used as a useful adjunct to improve the neuromuscular function of the upper limb. Cross-transfer of strength plays an important role in rehabilitation of unilateral injuries. The present research intended to evaluate the acute effect of low frequency WBV training on cross-transfer of electromyographic activity and hand muscles strength when the measurement was performed on the contralateral limb. This was a randomized crossover trial conducted in a clinical biomechanics laboratory. Twenty-eight healthy participants aging between 20 and 35 years were included who were involved in two sessions with two weeks of rest. The participants were randomly assigned in two groups as follows: 1) active WBV/sham WBV; 2) sham WBV/active WBV. The participants were asked to stand on the vibrating plate and pull its belt in a vibrating mode using their dominant hand. Then, after a two-week rest, they performed the same task in the vibrating mode (35 Hz). Grip strength and electromyography (root mean square) in flexor digitorum profundus (FDP), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), and extensor carpi ulnaris (ECU) muscles of the contralateral limb were measured before and after exercise in both phases. No significant change was observed in the electrical activity of FDP, FDS, ECR, ECU muscles, and hands' grip strength of the contralateral limb (P > 0.05). WBV (35 Hz) was not able to augment cross-transfer in electromyographic activity and neuromuscular performance of the upper limb. Further studies would help to explore these results for several sessions of WBV on cross-transfer of training.


Naturally-occurring bacterial cellulose-hyperbranched cationic polysaccharide derivative/MMP-9 siRNA composite dressing for wound healing enhancement in diabetic rats.
The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. STATEMENT OF SIGNIFICANCE: In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.


Factors influencing delay in initiating post-exposure prophylaxis for rabies prevention among animal bite victims: A cross sectional study.
The aim of this study was to identify the delay and the factors associated with delay in initiating post exposure prophylaxis. A consecutive sampling method was proceeded, and 199 patients attending the anti-rabies clinic with a history of animal bite reported at SMHS Hospital were the subjects of the study. Majority of the patients (72.36%) reported a delay within 6 h after exposure, 18.59% within (6-48) h and 9.04% after 48 h of exposure. Increasing the number of accessible anti-rabies clinics as well as increasing the awareness among general public about timely post exposure prophylaxis in the community are some of the factors that need to be implemented.


Lumbar hernia after breast reconstruction.
Lumbar hernia is a rare complication that can occur after breast reconstruction using a latissimus dorsi flap. The defect occurs within the superior lumbar triangle and may result in visceral incarceration. We report a 61-year-old female who presented with a left sided lumbar bulge and pain 7 years following a modified radical mastectomy and latissimus dorsi flap reconstruction. Computed tomography demonstrated a lumbar hernia with incarcerated colon. The patient underwent a successful laparoscopic repair with prosthetic mesh underlay. Lumbar hernias may be congenital, secondary to trauma or prior surgery. Imaging studies assist in excluding soft tissue tumors, infections, hematoma or abdominal wall denervation atrophy, which may also present as a lumbar bulge. Repair may be performed in an open, laparoscopic or retroperitoneoscopic approach. Laparoscopic lumbar hernia repair with mesh is a safe and feasible way to manage an uncommon complication after breast reconstruction with a latissimus flap.