Carbon nanotube mediated microscale membrane extraction.
We demonstrate that functionalized carbon nanotubes can be readily immobilized into the pore structure of a polymeric membrane, which can dramatically improve its performance in analytical scale membrane extraction. This was accomplished by injecting an aqueous dispersion of the nanotubes through a polypropylene hollow fiber under pressure. The nanotubes were trapped and held within the pores and served as sorbents facilitating solute exchange from the donor to the acceptor phase. The effectiveness of this carbon nanotube mediated process was studied by direct solvent enrichment of nonpolar organics, and also by selective extraction of organic acids via a supported liquid membrane. In both cases, the enrichment factor measured as the ratio of concentrations in the acceptor to the donor phases could be increased by more than 200%.


Enzymatic properties of overexpressed human hexokinase fragments.
Full-length hexokinase (HK; ATP: D-hexose 6-phosphotransferase, EC 188.8.131.52), a truncate form of the enzyme lacking the first 11 amino acids (HK-11aa) and the 50 kDa C-terminal half ('mini'-HK) containing the catalytic domain, were overexpressed and purified to homogeneity to investigate the influence of the N-terminal region of human hexokinase type I (HK) on its regulatory properties. All forms of the enzyme are catalytically active with the HK-11aa being the most active. All the forms of HK showed the same affinity for glucose and MgATP and were also inhibited by glucose 6-phosphate (Glc 6-P) competitively vs. MgATP with similar Kis (28.5-37 microM). Glucose 1,6-bisphosphate (Glc 1,6-P2) was also a strong inhibitor of all HKs without significant differences among the different truncate forms of the enzyme (Kis 49.5-59 microM). At low concentrations (0-3 mM), Pi was able to reverse the sugar phosphate inhibition of the full-length HK and HK-11aa but not of the 'mini'-HK. In contrast, at high concentrations Pi was an inhibitor of all the hexokinases investigated. These findings confirm that Pi has a low affinity binding site on the C-terminal of HK while counteracts glucose 6-phosphate inhibition by binding to or requiring the N-terminal half of the enzyme. The first 11 N-terminal amino acids influence the specific activity of HK but are unable to affect the kinetic properties investigated.


Bony injuries in association with minor head injury: lessons for improving the diagnosis of facial fractures.
One hundred consecutive admissions for minor head injury over a 12-week period in 1992 were analysed for all associated bony injuries. Fractures of the facial bones were found to be the commonest concurrent injury. A number of these were missed in the Accident and Emergency Department either due to inadequate radiographic views or incomplete recognition of clinical and radiological findings. A protocol for assessment of injury to the head and face is suggested.


Adenylyl cyclase deficient cr-1 (Crisp) mutant of Neurospora crassa: cyclic AMP-dependent nutritional deficiencies.
The inability to synthesize cyclic AMP drastically affects the nutritional metabolism of Neurospora crassa. The adenylyl cyclase-less mutant cr-1 (crisp) did not utilize several carbon sources, including glycerol, mannitol, arabinose, and casaminoacids. However, in glucose or acetate it grew as well as the wild type. The following evidence suggested that these nutritional deficiencies were a direct result of the cr-1 mutation: (i), in crosses to wild type they segregated together with the crisp morphological marker; (ii), cyclic AMP added to the cr-1 mutant growth medium overcame the nutritional deficiencies; (iii), the cyclic AMP effect was specific for the crisp mutant, for it was not observed with the wild type, nor with a spontaneous glycerol-utilizing cr-1 strain.


Spontaneous rupture of the urinary bladder (SRUB); A case report and review of literature.
Spontaneous urinary bladder rupture is a rare urological emergency. It is usually secondary to an underlying pathology and it is an uncommon complication of urosepsis. We report a case of spontaneous urinary bladder rupture as a complication of urosepsis in a 67 year old male patient, who was admitted as a case of left diabetic foot and urinary tract infection. A 67 year old male patient with a long standing indwelling urinary catheter and chronic cystitis developed acute peritonitis. Intraoperative finding was ruptured urinary bladder. A few cases of spontaneous urinary bladder rupture due to infection were found in literature. The majority of the patients present with diffuse abdominal pain, and tenderness due to chemical peritonitis. In the majority of cases the bladder perforation was diagnosed intra-operative. A diagnosis of spontaneous perforation of the bladder should be considered in patients presenting with an acute abdomen. The general surgeon is more likely than the urologist to encounter such patients in the first instance. There should be a high index of suspicion in patients with an acute abdomen and have associated urinary bladder condition.


An open randomized study comparing disulfiram and acamprosate in the treatment of alcohol dependence.
To compare the efficacy of acamprosate (ACP) and disulfiram (DSF) for preventing alcoholic relapse in routine clinical practice. One hundred alcoholic men with family members who would encourage medication compliance and accompany them for follow-up were randomly allocated to 8 months of treatment with DSF or ACP. Weekly group psychotherapy was also available. The psychiatrist, patient, and family member were aware of the treatment prescribed. Alcohol consumption, craving, and adverse events were recorded weekly for 3 months and then fortnightly. Serum gamma glutamyl transferase was measured at the start and the end of the study. At the end of the trial, 93 patients were still in contact. Relapse (the consumption of >5 drinks/40 g of alcohol) occurred at a mean of 123 days with DSF compared to 71 days with ACP (P = 0.0001). Eighty-eight per cent of patients on DSF remained abstinent compared to 46% with ACP (P = 0.0002). However, patients allocated to ACP had lower craving than those on DSF (P = 0.002). DSF is superior to ACP for preventing relapse in alcohol-dependent men with good family support. Further comparisons between these two drugs in different treatment settings and populations are warranted.


[Qualitative analysis of eight suicide notes of elderly people].
We analize and classify eight suicide notes left by elderly patients who attempted suicide; older adults leave more frequently suicide notes. We used the typologie created by Jacobs in 1967 who classifies the notes in five categories. The issues which frequently appear are: physical illnes, cronic pain, loneliness, disability, depression and isolation.


Relationship between uric acid and lipid accumulation product index by gender in Korean adults: The 2016 Korean National Health and Nutrition Examination Survey.
The present study assesses the relationship between uric acid (UA) and lipid accumulation product index (LAP) by gender among Korean adults. Data from 5670 subjects (2463 men and 3207 women) in the Korean National Health and Nutrition Examination Survey (KNHANES VII-1) 2016 were analyzed. LAP was divided into four quartiles (Q1-Q4). There were several key findings. Compared with Q1, in the overall population, the odds ratios (ORs) of hyperuricemia (UA ≥ 7.0 mg/dL in men or UA ≥ 6.0 mg/dL in women) were significantly higher in Q2 [1.847 (95% confidence interval [CI], 1.325-2.575)], Q3 [3.050 (95% CI, 2.216-4.198)], and Q4 of LAP [6.367 (95% CI, 4.658-8.704)]. In men, the ORs of hyperuricemia were significantly higher in Q2 [1.658 (95% CI, 1.162-2.367)], Q3 [2.341 (95% CI, 1.656-3.308)], and Q4 [4.633 (95% CI, 3.290-6.525)] than Q1. In women, the ORs of hyperuricemia were significantly higher in Q2 [2.254 (95% CI, 1.085-4.680)], Q3 [5.402 (95% CI, 2.735-10.668)], and Q4 [11.025 (95% CI, 5.620-21.628)] than Q1. In addition, UA levels were positively associated with LAP level in men (r = 0.218; p < 0.001), women (r = 0.261; p < 0.001), and the overall population (r = 0.260; p < 0.001). Hyperuricemia was positively associated with LAP in Korean men and women.


Critical review on phytoremediation of polyfluoroalkyl substances from environmental matrices: Need for global concern.
Poly- and perfluoroalkyl substances (PFAS) are a class of emerging organic contaminants that are impervious to standard physicochemical treatments. The widespread use of PFAS poses serious environmental issues. PFAS pollution of soils and water has become a significant issue due to the harmful effects of these chemicals both on the environment and public health. Owing to their complex chemical structures and interaction with soil and water, PFAS are difficult to remove from the environment. Traditional soil remediation procedures have not been successful in reducing or removing them from the environment. Therefore, this review focuses on new phytoremediation techniques for PFAS contamination of soils and water. The bioaccumulation and dispersion of PFAS inside plant compartments has shown great potential for phytoremediation, which is a promising and unique technology that is realistic, cost-effective, and may be employed as a wide scale in situ remediation strategy.


Oxidative stress activates both Src-kinases and their negative regulator Csk and induces phosphorylation of two targeting proteins for Csk: caveolin-1 and paxillin.
Csk negatively regulates Src family kinases (SFKs). In lymphocytes, Csk is constitutively active, and is transiently inactivated in response to extracellular stimuli, allowing activation of SFKs. In contrast, both SFKs and Csk were inactive in unstimulated mouse embryonic fibroblasts, and both were activated in response to oxidative stress. Csk modulated the oxidative stress-induced, but not the basal SFK activity in these cells. These data indicate that Csk may be more important for the return of Src-kinases to the basal state than for the maintenance of basal activity in some cell types. Csk must be targeted to its SFK substrates through an SH2-domain-mediated interaction with a phosphoprotein. Our data indicate that caveolin-1 is one of these targeting proteins. SFKs bind to caveolin-1 and phosphorylate it in response to oxidative stress and insulin. Csk binds specifically to the phosphorylated caveolin-1 and attenuates its stress-induced phosphorylation. Importantly, phosphocaveolin was one of two major phosphoproteins associated with Csk after incubation with peroxide or insulin. Paxillin was the other. Activation/rapid attenuation of SFKs by Csk is required for actin remodeling. Caveolin-1 is phosphorylated at the ends of actin fibers at points of contact between the actin cytoskeleton and the plasma membrane, where it could in part mediate this attenuation.


Influenza A virus induced bacterial otitis media is independent of virus tropism for α2,6-linked sialic acid.
Otitis media (OM) affects ≥80% of children before the age of three. OM can arise following co-infection with influenza A virus (IAV) and the bacterium Streptococcus pneumoniae. We have previously shown that H3 IAV strains (such as Udorn/72) induced a higher rate of bacterial OM than H1 strains (such as PR8/34). This was associated with more efficient replication of H3 strains in the middle ear. Here, we assess if the increased replication of IAV strains such as Udorn/72 in the middle ear is dependent upon the binding of the viral HA to α2,6-linked sialic acid. Using murine and in vitro models, the present study shows that recognition of α2,6-linked sialic acid was not required to facilitate bacterial OM. Taken together, these data suggest that other features of the HA mediate bacterial OM.


Use of capnography to verify emergency ventilator sharing in the COVID-19 era.
Exacerbation of COVID-19 pandemic may lead to acute shortage of ventilators, which may require shared use of ventilator as a lifesaving concept. Two model lungs were ventilated with one ventilator to i) test the adequacy of individual tidal volumes via capnography, ii) assess cross-breathing between lungs, and iii) offer a simulation-based algorithm for ensuring equal tidal volumes. Ventilation asymmetry was induced by placing rubber band around one model lung, and the uneven distribution of tidal volumes (VT) was counterbalanced by elevating airflow resistance (HR) contralaterally. VT, end-tidal CO2 concentration (ETCO2), and peak inspiratory pressure (Ppi) were measured. Unilateral LC reduced VT and elevated ETCO2 on the affected side. Under HR, VT and ETCO2 were re-equilibrated. In conclusion, capnography serves as simple, bedside method for controlling the adequacy of split ventilation in each patient. No collateral gas flow was observed between the two lungs with different time constants. Ventilator sharing may play a role in emergency situations.


Conserved spatial organization of FG domains in the nuclear pore complex.
Selective transport through the nuclear pore complex (NPC) requires nucleoporins containing natively unfolded phenylalanine-glycine (FG) domains. Several differing models for their dynamics within the pore have been proposed. We characterize the behavior of the FG nucleoporins in vivo using polarized fluorescence microscopy. Using nucleoporins tagged with green fluorescent protein along their FG domains, we show that some of these proteins are ordered, indicating an overall orientational organization within the NPC. This orientational ordering of the FG domains depends on their specific context within the NPC, but is independent of active transport and cargo load. For most nups, behavior does not depend on the FG motifs. These data support a model whereby local geometry constrains the orientational organization of the FG nups. Intriguingly, homologous yeast and mammalian proteins show conserved behavior, suggesting functional relevance. Our findings have implications for mechanistic models of NPC transport.


New trends in LC protein ligand screening.
The diversity of small molecules available to produce truly innovative drugs associated with the wealth of known biological targets calls for key strategies in protein ligand screening. This review encompasses the recently developed bioaffinity-based strategies. A critical view of the use of zonal, frontal, and nonlinear chromatography with immobilized proteins is given. The association of these elution modes with the ligand fishing method, which uses nanomagnetics particles, is also addressed. A series of applications and how these new screening strategies can be used to determine the function, affinity, and activity parameters of proteins is discussed.


Global Health in Radiation Oncology: The Emergence of a New Career Pathway.
The massive global shortfall in radiotherapy equipment and human resources in developing countries is an enormous challenge for international efforts in cancer control. This lack of access to treatment has been long-standing, but there is now a growing consensus about the urgent need to prioritize solutions to this problem and that a global strategy is required for them to be successful. An essential element of making radiotherapy universally accessible is a coordinated approach to clinical training and practice. This has been recently recognized by many university departments and clinical training programs. However, formalized training and career promotion tracks in global health within radiation oncology have been slow to emerge, thereby limiting the sustained involvement of students and faculty, and restricting opportunities for leadership in this space. We examine here potential structures and benefits of formalized global health training in radiation oncology. We explore how defining specific competencies in this area can help trainees and practitioners integrate their activities in global health within their existing roles as clinicians, educators, or scientists. This would also help create a new global health track for academic advancement, which could focus on such domains as implementation science, health service, and advocacy. We discuss how effective mentorship models, international partnerships, and institutional twinning arrangements support this work and explore how new resources and funding models might be used to further develop and expand radiation oncology services globally.


Surgery for acute ascending aortic dissection: closed versus open distal aortic repair.
One hundred twelve consecutive patients with acute ascending aortic dissection and submitted to immediate surgery were retrospectively analyzed with regard to perioperative mortality and morbidity. The patients were divided into two groups according to whether distal aortic repair was carried out by the open procedure (using deep hypothermic circulatory arrest, group A: 68 patients) or by the closed technique (without circulatory arrest, group B: 44 patients). Patients' ages ranged from 24 to 78 years (mean 57.4 years). No significant difference was found between the two groups in terms of age and sex distribution. However, the prevalence in the extent of clinical and anatomical alterations was significantly higher in group A (hemodynamic instability, pericardial tamponade and neurological deficit). The duration of hypothermic circulatory arrest for group A patients averaged 25 min and ranged from 12 to 65 min. The overall perioperative mortality was 17% (19/112 patients); it was 20.6% (14/68) in group A and 11.4% (5/44) in group B; the difference was not statistically significant but consistent with a clear trend. The trend towards a higher mortality in group A mainly reflected the more severe and complex anatomical characteristics and could not be attributed to the circulatory arrest per se. The period of deep hypothermic circulatory arrest in the survivors (25 min) was similar to that of the group with lethal outcome (32 min). Among the non-lethal complications, however, group A patients more frequently showed clinical signs consistent with cerebral injury: apart from the transient symptoms suggestive in reversible diffuse cerebral damage, five patients in group A had a permanent focal neurological deficit (versus one patient in group B).(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical study of the 1CU accommodating intraocular lens.
To compare the near functional capacities of patients with an accommodating intraocular lens (IOL) with those of patients with a conventional monofocal IOL. Department of Ophthalmology, University of Chieti, Chieti, Italy. This prospective double-blind case-control study comprised 42 eyes that had phacoemulsification and implantation of 1 of 2 types of IOLs: HumanOptics accommodating 1CU(R) (study group) and Eurocrystal IFP 3G 6.00 (control group). The main outcome measures were subjective refraction, uncorrected distance acuity, best corrected distance acuity, distance corrected near acuity at 40 cm, best corrected near acuity at 40 cm, and subjective amplitude of accommodation. Patients were examined 7, 30, 90, and 180 days after surgery. Postoperatively, both groups had excellent uncorrected distance acuity, best corrected distance acuity, and best corrected near acuity. In the study group, the mean distance corrected near acuity (Jaeger) was 5.43 +/- 0.98 (SD) (range 4 to 7) at 7 days, 2.33 +/- 0.48 (range 2 to 3) at 1 and 3 months, and 3.66 +/- 2.12 (range 2 to 7) at 6 months. In the control group, the mean distance corrected near acuity was 7.43 +/- 0.50 (range 7 to 8) during the entire follow-up. The differences between the groups was statistically significant (P<.001). The mean amplitude of accommodation was 0.00 diopter (D) in the control group and 1.14 +/- 0.44 D (range 0.75 to 2.00 D) in the study group at 7 days, 2.36 +/- 0.28 D (range 2.00 to 2.75 D) at 30 and 90 days, and 1.90 +/- 0.77 D (range 0.75 to 2.75 D) at 6 months. The 1CU accommodating IOL provided better useful spectacle-free near visual acuity than the conventional monofocal IOL. However, the accommodating mechanism can play a role in capsule fibrosis.


Highly increased natural killer cell number and lytic activity in the murine peripheral blood and lungs after interferon induction in vivo.
We have studied the effect of interferon in vivo (induced by polyinosinic-polycytidylic acid (pIC] on the natural killer (NK) cell lytic activity and on the numbers of large granular lymphocytes (LGL) and target-binding cells (TBC) in different lymphoid compartments. One day after the pIC induction the spleen contained two- to four-fold increased lytic activity without a significant change in percentages of TBC and LGL. In the peripheral blood the lytic activity was 12- to 40-fold higher, and a concomitant clear increase in the number of LGL and TBC was seen. In the lungs the increase in lytic activity was 8- to 16-fold and in the number of LGLs ca. 3-fold. These results demonstrate that not only the lytic activity of the pre-existing NK cells but also the total amount of NK cells is clearly elevated in the body, but this could be seen more significantly in other highly NK-active organs than the spleen.


Modeling differences in the vibration response characteristics of the human body.
Mathematical models may provide a useful tool for the development and evaluation of seating systems for vibration mitigation. A five-degree-of-freedom (DOF) model was formulated based on the measured driving-point impedance and transmissibilities of major anatomical structures contributing to the observed resonance behaviors. The model was limited in its ability to simulate differences observed in the resonance behaviors of a broader population and was unable to simulate the multiple resonances observed in the thigh. This paper describes the effectiveness of a modified five DOF model in simulating the major resonance behaviors observed in the population using representative data from a 56 kg female and 75 kg male. In addition, the model was also evaluated for its ability to predict the effects of selected seat cushions. The modified lumped-parameter model improved the peak chest and spine transmissibility simulations. The model was effective in simulating both the lower impedance peak observed in the primary resonance region (4-8 Hz) and the prevalent impedance peak observed in the second resonance region (7-10 Hz) in the smaller subjects. However, the model was not effective in predicting the dampening observed in the second resonance peak with the use of cushions. Redistribution of the model coefficients for the legs and the consideration of coupling between the legs and other anatomical structures may further improve the ability of the lumped-parameter model to predict the effects of seating systems on vibration transmission in the human body.


Single-Pulse X-ray Acoustic Computed Tomographic Imaging for Precision Radiation Therapy.
High-precision radiation therapy is crucial for cancer treatment. Currently, the delivered dose can only be verified via simulations with phantoms, and an in-tumor, online dose verification is still unavailable. An innovative detection method called x-ray-induced acoustic computed tomography (XACT) has recently shown the potential for imaging the delivered radiation dose within the tumor. Prior XACT imaging systems have required tens to hundreds of signal averages to achieve high-quality dose images within the patient, which reduces its real-time capability. Here, we demonstrate that XACT dose images can be reproduced from a single x-ray pulse (4 µs) with sub-mGy sensitivity from a clinical linear accelerator. By immersing an acoustic transducer in a homogeneous medium, it is possible to detect pressure waves generated by the pulsed radiation from a clinical linear accelerator. After rotating the collimator, signals of different angles are obtained to perform a tomographic reconstruction of the dose field. Using 2-stage amplification with further bandpass filtering increases the signal-to-noise ratio (SNR). Acoustic peak SNR and voltage values were recorded for singular and dual-amplifying stages. The SNR for single-pulse mode was able to satisfy the Rose criterion, and the collected signals were able to reconstruct 2-dimensional images from the 2 homogeneous media. By overcoming the low SNR and requirement of signal averaging, single-pulse XACT imaging holds great potential for personalized dose monitoring from each individual pulse during radiation therapy.


Cytokines transcript levels in lung and lymphoid organs during genotype 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection.
Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most economically important diseases of swine. PRRS virus (PRRSV) infection in the pig is characterized by a weak or absent host innate immune response. The underlying mechanisms of PRRSV pathogenesis are still unclear. The analysis of transcript levels represents an alternative to immunoassays for the detection of cytokines that sometimes are difficult to detect due to their low amounts. This study sets out to determine the differences in pathogenesis and the immune response between lung, tonsil, tracheobronchial lymph node (Tb-LN) and retropharyngeal LN (Rf-LN) of PRRSV 2982 strain infected pigs. PRRSV strain 2982 avoided the onset of an effective innate immune response, especially in PRRSV main target (lung) and reservoir (tonsil) organs. PRRSV lead to an impaired expression of IFN-α and TNF-α gene expression, which finally induced a weak and delayed adaptive immune response through an inefficient IL-12 and IFN-γ expression. Finally, PRRSV replication favored the expression of the anti-inflammatory IL-10 cytokine in infected pigs.


Biomonitoring and phytoremediation potential of the leaves, bark, and branch bark of street trees for heavy metal pollution in urban areas.
Tree tissues can accumulate heavy metals from the environment. We therefore aimed to evaluate the presence of the metals Pb, Cr, Mn, Cu, and Zn in four street tree species, namely Ailanthus altissima, Broussonetia papyrifera, Pinus tabuliformis, and Rhus typhina, along the highway side of Beijing, China. Sampling from the leaves, trunk bark, and branch annual segment bark of trees was conducted in the summer of 2021, and the concentration of heavy metals was determined. The results revealed the highest average concentration of total heavy metals in the R. typhina leaves (23.724 mg/kg) and barks (14.454 mg/kg). The maximum bio-concentration factor was noted for Zn in the B. papyrifera leaves (0.36) and P. tabuliformis barks (0.21). The maximum comprehensive bio-concentration index was observed for the B. papyrifera leaves (0.225) and P. tabuliformis bark (0.108). The maximum metal accumulation index was measured in the R. typhina leaves (29.682) and bark (12.407). Based on the air-originated metals, P. tabuliformis showed the highest dust collection capacity. In general, B. papyrifera and P. tabuliformis exhibited the highest absorption rate from the soil relative to the other studied species. R. typhina demonstrated the strongest phytoremediation ability for heavy metal pollution in air. In addition, our results proved that the branch annual segment bark of P. tabuliformis is an excellent record carrier that can be used to monitor heavy metal pollution in a specific time duration in an urban area.


Comparison of plastic and Orfit masks for patient head fixation during radiotherapy: precision and costs.
Two widely used immobilization systems for head fixation during radiotherapy treatment for ear-nose-throat (ENT) tumors are evaluated. Masks made of poly vinyl-chloride (plastic) are compared to thermoplastic masks (Orfit) with respect to the accuracy of the treatment setup and the costs. For both types of material, a cut-out (windows corresponding to treatment fields) and a full mask (not cut out) are considered. Forty-three patients treated for ENT tumors were randomized into four groups, to be fixed by one of the following modalities: cut-out plastic mask (12 patients), full plastic mask (11 patients), cut-out Orfit mask (10 patients), and full Orfit mask (10 patients). Reproducibility of the treatment setup was assessed by calculating the deviations from the mean value for each individual patient and was demonstrated to be identical for all subgroups: no differences were demonstrated between the plastic (s = 2.1 mm) and the Orfit (s = 2.1 mm) group nor between the cut-out (s = 2.0 mm) and not cut-out (s = 2.1 mm) group. The transfer chain from similar to treatment unit was checked by comparing portal images to their respective simulation image, and no differences between the four subgroups (s = +/- 3.5 mm) could be detected. A methodology was described to compare the costs of both types of masks, and illustrated with the data for a department. It was found that Orfit masks are a cheaper alternative than plastic masks; they require much less investment expenses and the workload and material cost of the first mask for each patient is also lower. Cut-out masks are more expensive than full masks, because of the higher workload and the additional material required for second and third masks that are required in case of field modifications. No substantial difference in patient setup accuracy between both types of masks was detected, and cutting out the masks had no impact on the fixing capabilities. A first Orfit mask will typically be a cheaper alternative than a plastic mask for most departments (lower fixed and variable costs). The higher material cost of the subsequent Orfit masks, compared to the plastic masks, offset the lower investment expenses.


Comparative effectiveness research on proximal femoral nail versus dynamic hip screw in patients with trochanteric fractures: a systematic review and meta-analysis of randomized trials.
The treatments for trochanteric fractures try to regain early mobility and limit morbidity and risk of reoperations. The most currently used dynamic hip screw (DHS) and the proximal femoral nail (PFN) are both with pros and cons. We aimed to assess the comparative effectiveness of these interventions for trochanteric fractures by evaluating the surgical performance and postoperative outcomes. PubMed, Web of Science and Cochrane Central Register were searched for RCTs comparing DHS and PFN for trochanteric fractures. All selected studies and the risk of bias were assessed. Clinical data including operative time, intraoperative blood loss, intraoperative fluoroscopy time, successful closed reduction and complications like nonunion, implant failure and reoperation were recorded. Random-effects models were used in Review Manager software, and GRADE was applied for the interpretation of the evidence. From 286 identified trials, twelve RCTs including 1889 patients were eligible for inclusion; six RCTs directly comparing DHS with PFN, while other six compared DHS with proximal femoral nail antirotation (PFNA). Compared to DHS, PFN had shorter operative time and led to less intraoperative blood loss. However, DHS need less intraoperative fluoroscopy time than PFN. No difference was seen for the achievement of closed reduction. For risk of postoperative complications, no difference was seen between PFN and DHS for non-union, risk of implant failure and revision surgery. PFN(A) resulted in a shorter operative time and less intraoperative blood loss compared to DHS. However, no difference was seen for postoperative complications. Trial registration PROSPERO: CRD42021239974.


[Gastric and pancreatic cancers: Will neoadjuvant (chemo)radiotherapy replace adjuvant chemoradiotherapy?]
For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal.


New Marginal Spectrum Feature Information Views of Humpback Whale Vocalization Signals Using the EMD Analysis Methods.
Marginal spectrum (MS) feature information of humpback whale vocalization (HWV) signals is an interesting and significant research topic. Empirical mode decomposition (EMD) is a powerful time-frequency analysis tool for marine mammal vocalizations. In this paper, new MS feature innovation information of HWV signals was extracted using the EMD analysis method. Thirty-six HWV samples with a time duration of 17.2 ms were classified into Classes I, II, and III, which consisted of 15, 5, and 16 samples, respectively. The following ratios were evaluated: the average energy ratios of the 1 first intrinsic mode function (IMF1) and residual function (RF) to the referred total energy for the Class I samples; the average energy ratios of the IMF1, 2nd IMF (IMF2), and RF to the referred total energy for the Class II samples; the average energy ratios of the IMF1, 6th IMF (IMF6), and RF to the referred total energy for the Class III samples. These average energy ratios were all more than 10%. The average energy ratios of IMF1 to the referred total energy were 9.825%, 13.790%, 4.938%, 3.977%, and 3.32% in the 2980-3725, 3725-4470, 4470-5215, 10,430-11,175, and 11,175-11,920 Hz bands, respectively, in the Class I samples; 14.675% and 4.910% in the 745-1490 and 1490-2235 Hz bands, respectively, in the Class II samples; 12.0640%, 6.8850%, and 4.1040% in the 2980-3725, 3725-4470, and 11,175-11,920 Hz bands, respectively, in the Class III samples. The results of this study provide a better understanding, high resolution, and new innovative views on the information obtained from the MS features of the HWV signals.


Explantation/exchange of the components of a new fluid-filled, modular, accommodating IOL.
To evaluate the ease of replacement and capsular stability of a new fluid-filled, modular, accommodating intraocular lens (IOL) system composed of a monofocal base lens with a fluid lens clipped inside of it. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Experimental study. Five New Zealand rabbits underwent bilateral phacoemulsification with implantation of the test lens (Juvene, LensGen, Inc.) in both eyes (4 rabbits), or a control IOL in 1 eye (AcrySof, Alcon Laboratories, Inc.) and the test IOL in the other (1 rabbit). At 2 weeks, the 4 rabbits with bilateral Juvene IOLs had the clipped-in fluid lens exchanged for a new fluid lens in 1 eye, and the base and fluid lenses exchanged for a control lens in the contralateral eye. Slitlamp examinations were performed weekly for 4 weeks. The globes were enucleated and evaluated with ultrasound biomicroscopy, grossly from the posterior Miyake-Apple view, and histopathologically. Explantation/exchange of the fluid lens was considered straightforward by the surgeon. Explantation of the base lens (4) was also safely performed, albeit more demanding, without any signs of damage to the capsular bag under clinical, ultrasound biomicroscopy, and pathological examination in the exchanged eyes. Less capsular bag opacification was observed with the Juvene lens system. Explantation/exchange of the fluid lens component, or both fluid and base lenses, of this new lens system can be safely accomplished if necessary, because of its modular design and the relative lack of postoperative capsular bag opacification associated with it.


Prognostic and clinicopathological significance of cytocapsular tubes in oral squamous cell carcinoma.
Cytocapsular tubes (CTs) provide membranous channels for cancer cells interconnection and multidirectional locomotion, which facilitate cancer cell transportation and metastasis. However, the clinicopathological significance of CTs has not been documented in oral squamous cell carcinoma (OSCC). Herein, we aimed to identify CTs and assess their clinicopathological significance in OSCC. Operetta CLS™ high-content analysis system was used to detect the CTs originated from OSCC cells cultured in a 3D Matrigel matrix. Then, pan-cadherin and γ-actin immunostaining were performed to identify CTs in 4NQO-induced murine OSCC tissues, OSCC xenografts and 88 human primary OSCC samples. Finally, the prognostic value and clinicopathological significance of CTs in OSCC were further examined by using the Kaplan-Meier method and Cox regression analysis. CTs were observed in OSCC cells in a 3D Matrigel matrix. In vivo, CTs were frequently identified in 4NQO-induced murine OSCC tissues, OSCC xenografts and human primary OSCC samples. CTs density was significantly associated with T stage, lymph node metastasis, differentiation, invasive depth, tumor budding, TNM stage and tumor recurrence. Importantly, the high-CTs density indicated a decreased overall survival (OS) and progression-free survival (PFS) in OSCC patients. Cox regression models showed that CTs could serve as a prognostic factor for OS and PFS. CTs, which are correlated with the cell migration and invasion, can be readily identified in OSCC and appear to be a novel biomarker for patients at risk of metastasis.


Isolation of cupanioside, a novel cytotoxic and antibacterial long-chain fatty alcohol glycoside from the bark of Cupania glabra.
The crude dichloromethane extract from the stem bark of Cupania glabra (Sapindaceae), showed in vitro cytotoxic activity against Hep G2, MDA-MB-231, Hs 578T, MCF-7, and PC-3 cells, and antibacterial activity against Bacillus cereus, Staphylococcus aureus, and Escherichia coli. Bioactivity-directed fractionation led to isolation of the new 1-O-[2'',3'',4''-tri-O-acetyl-alpha-L-rhamnopyranosyl-(1-->2)-beta- D-glucopyranosyl]-hexadecanol (cupanioside) as the cytotoxic agent. The structure was elucidated by analysis of 2D-NMR spectra.


Non-conventional therapeutical approaches to acne vulgaris related to its association with metabolic disorders.
The ever-increasing frequency of metabolic syndrome (MetS) is still a major challenge of the public health care system, worldwide. In recent years, researchers have been drawn to the uncommon (at first look) link between skin illnesses and MetS. Because of the pro-inflammatory mechanisms and insulin resistance (IR) that are upregulated in metabolic syndrome, many skin disorders are correlated to metabolic dysfunctions, including acne vulgaris. A comprehensive understanding of the link between MetS and acne vulgaris may contribute to the development of new treatment strategies. The current review focuses on dietary and therapeutic interventions and assesses the effect of various approaches such as improving diet by avoiding certain food products (i.e., milk and chocolate) or increasing the intake of others (i.e., food products rich in omega-3 fatty acids), metformin administration, therapy with plant extracts, plant essential oils, and probiotic supplementation on the improvement of certain acne vulgaris severity parameters. These therapeutic approaches, when combined with allopathic treatment, can improve the patients' quality of life.


Keratinolytic fungi of wadi Qena in Egypt.
Forty-six soil samples collected from different sites of wadi Qena were examined for keratinophilic fungi using the hair baiting technique. Thirty-two species in addition to one variety of each of A. nidulans and A. flavus which belong to eighteen genera were recovered. Aspergillus, Chrysosporium, Penicillium, Microsporum and Fusarium were the most frequent genera developed from baited soils.


Assessment of DNA Methylation and Oxidative Changes in the Heart and Brain of Rats Receiving a High-Fat Diet Supplemented with Various Forms of Chromium.
The aim of the study was to determine how feeding rats a high-fat diet supplemented with various forms of chromium affects DNA methylation and oxidation reactions as well as the histology of heart and brain tissue. The rats received standard diet or high-fat diet and chromium at 0.3 mg/kg body weight (BW) in form of chromium (III) picolinate, chromium (III)-methionine, or nano-sized chromium. The content of malondialdehyde (MDA), protein carbonyl (PC), and 8-hydroxydeoxyguanosine (8-OHDG), the level of global DNA methylation and the activity of selected DNA repair enzymes were determined in the blood. In the brain and heart, the content of MDA, PC, 8-OHDG, and levels of global DNA methylation were determined. The brain was subjected to histological examination. The use of a high-fat diet was found to intensify epigenetic changes and oxidation reactions in the heart and brain. It was concluded that epigenetic changes and oxidation of lipids, proteins, and DNA in the heart and brain of rats resulting from the use of a high-fat diet cannot be limited by supplementing the diet with chromium. It was established that the use of chromium to supplement a high-fat diet intensifies the negative epigenetic and oxidative changes in the heart and brain, especially in the case of chromium nanoparticles.


Combined Endovascular and Endoscopic Approach for Treatment of Concomitant Sphenoid Sinus Giant Traumatic Aneurysm and Direct Carotid Cavernous Fistulas.
Direct carotid cavernous fistulas (CCFs) and sphenoid sinus traumatic aneurysms are well-known pathologies that can present concomitantly in rare cases. Patients with both lesions are usually symptomatic from both the CCF and the traumatic aneurysm. Symptoms include proptosis, chemosis, bruit, epistaxis, visual field defects, and loss of vision. Surgical treatment can be challenging, and for most cases an endovascular approach is the treatment of choice. We present an unusual case of a direct CCF with an associated large traumatic aneurysm in the sphenoid sinus due to a history of trauma presenting with unusual symptoms that was treated by a combined endoscopic and endovascular approach. Concurrent occurrence of a traumatic CCF and traumatic aneurysm of the cavernous segment is extremely rare. Early diagnosis and treatment of these lesions are important considering their high mortality rate. Complete occlusion of the fistula and aneurysm while preserving the patency of the carotid artery via an endovascular approach is the treatment of choice for these lesions.


ABCA7 links sterol metabolism to the host defense system: Molecular background for potential management measure of Alzheimer's disease.
ATP-binding cassette transporter (ABC) A7 is a membrane protein that belongs to the large family of ABC transporters. It is 54% homologous in amino acid residue sequence to ABCA1 which mediates biogenesis of plasma high density lipoprotein (HDL) from cellular phospholipid and cholesterol with extracellular helical apolipoproteins such as apolipoprotein (apo) A-I. When transfected and expressed, ABCA7 also mediates generation of HDL-like particles but small and of less cholesterol content. However, endogenous ABCA7 is unlikely involved in HDL biogenesis and rather to regulate the host-defense system such as phagocytotic function of the cells. ABCA1 expression is regulated by cellular cholesterol levels, positively by the liver X receptor (LXR) in extrahepatic peripheral cells. However, it is modulated dually in the liver being relevant to transport of cholesterol for its catabolism; positively by LXR and negatively by sterol regulatory element binding protein (SREBP) or hepatic nuclear factor 4α (HNF4α). In contrast, ABCA7 expression was shown to be regulated negatively by the SREBP system so that decrease of cell cholesterol enhances ABCA7 function such as cellular phagocytotic reaction, suggesting that it links cholesterol metabolism to the host defense system. The interest is being build up in ABCA7 as its genomic diversity has been found related to a risk for late-onset Alzheimer's diseases. More recent findings indicate that ABCA7 is involved in metabolism of amyloid β peptide including its phagocytotic clearance. Accordingly, modulation of ABCA7 activity by manipulating cholesterol metabolism may open a new path for management of Alzheimer's disease.


A Systematic Review of Outcomes Following Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has increasingly become a significant concern for patients. Focus thus far has been on understanding pathogenesis and establishing treatment pathways. There has been less attention on the assessment of long-term treatment outcomes. The purpose of this study was to perform a systematic review to assess published data on treatment outcomes for BIA-ALCL. Using PRISMA guidelines, a systematic search of the literature was carried out from January 1997 to January 2021 using the Web of Science (PubMed) and Ovid Medline. Included in the review were any studies on the management and follow-up of patients, including disease status at a minimum of 18 months following treatment. A total of 39 articles matched the inclusion criteria. However, 94% of patients were managed with explantation and capsulectomy. Then, 39% of patients had adjuvant chemotherapy, 19% radiotherapy, 6% autologous stem cell transplant, and 4% immunotherapy. The mean follow-up was 19 months (range 3-36 months), and 69% of patients were reported to be alive at 18 months. The mainstay of treatment was surgical - en bloc capsulectomy with adjuvant treatment for advanced disease. Robust survival data based on high-level evidence are challenging to establish in BIA-ALCL. Early diagnosis and en bloc capsulectomy with negative margins, whilst considering the need for adjuvant treatment, particularly targeted immune therapy in advanced disease represents the consistent forms of treatment. National databases, prospective studies, and treatment of patients in tertiary centres are all recommended to improve the quality of the research available in the management of BIA-ALCL.


Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.
As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.


Compensating behaviors, regret, and heterogeneity in the dynamics of smoking behavior.
This paper studied smoking behavior in the context of the interactions among health, smoking, exercise and seeking medical care using a microeconomic model. Based on a dynamic optimal choice theory, a simultaneous equation system was used in the empirical estimation. This study found that smokers with longer smoking history tend to have extra incentives to maintain or improve their health. It was found that they tend to use more medical services and to be more active in exercise than smokers with shorter smoking history. Health status nonlinearly affects smoking decisions. Quitting incentives can be "curative" or "preventive", depending on one's health status. Light smokers' addiction is qualitatively and quantitatively different from heavy smokers'.


Association among cigarette smoking, metabolic syndrome, and its individual components: the metabolic syndrome study in Taiwan.
Insulin resistance is a common feature of metabolic syndrome. Smokers are at great risk of developing insulin resistance. Theoretically, smoking status should be associated with metabolic syndrome. This study aimed to explore the association among cigarette smoking, metabolic syndrome, and its individual components. Information of participants regarding previous and current diseases, family history of disease, smoking habits, alcohol consumption, betel nut chewing, and physical activity status were gathered from self-reported nutrition and lifestyle questionnaires. The fasting plasma glucose, triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, blood pressure, and anthropometric indices in each patient were measured. Data of 1146 male subjects were analyzed. Individuals who currently smoked had a higher prevalence of metabolic syndrome than those who had never smoked and those who had quit smoking. The adjusted odds ratios of current smoking amount showed a statistically significant dose-dependent association with metabolic syndrome, high triglyceride level, and low HDL-C level. Current smokers who smoke > or =20 pack-years have a significantly increased risk of developing metabolic syndrome, high triglyceride level, and low HDL-C level. The higher risk of development of metabolic syndrome, high triglyceride level, and low HDL-C level was insignificant in former smokers. In conclusion, this community-based study supports the view that smoking is associated with metabolic syndrome and its individual components. Smoking cessation is beneficial to metabolic syndrome and its individual components.


[Metformin associates lactic acidosis].
Metformin Associates lactic acidosis (MALA) is a metabolic acidosis with higher anion gap, high levels of blood lactates and treatment by metformin. MALA is a very rare entity but is associated with high mortality (30 to 50%). The extrarenal blood purification may be necessary in emergency. Relatively good clinical tolerance contrasts with a very elevated serum lactate. There is always a trigger and hypovolemia is prevalent. MALA often occurs when its prescription is not indicated (renal failure, cardiac failure, hypovolemia, or patient aged over 80 years). Metformin must be stopped in situations of acute hypovolemia or frail patients as diuretics or blockers of the rennin-angiotensin-aldosterone system.


A repeatable and quantitative DNA metabarcoding assay to characterize mixed strongyle infections in horses.
Horses are ubiquitously infected by a diversity of gastro-intestinal parasitic helminths. Of particular importance are nematodes of the family Strongylidae, which can significantly impact horse health and performance. However, knowledge about equine strongyles remains limited due to our inability to identify most species non-invasively using traditional morphological techniques. We developed a new internal transcribed spacer 2 (ITS2) DNA metabarcoding 'nemabiome' assay to characterise mixed strongyle infections in horses and assessed its performance by applying it to pools of infective larvae from fecal samples from an experimental herd in Kentucky, USA and two feral horse populations from Sable Island and Alberta, Canada. In addition to reporting the detection of 33 different species with high confidence, we illustrate the assay's repeatability by comparing results generated from aliquots from the same fecal samples and from individual horses sampled repeatedly over multiple days or months. We also validate the quantitative potential of the assay by demonstrating that the proportion of amplicon reads assigned to different species scales linearly with the number of larvae present. This new tool significantly improves equine strongyle diagnostics, presenting opportunities for research on species-specific anthelmintic resistance and the causes and consequences of variation in mixed infections.


Conformation of a trimannoside bound to mannose-binding protein by nuclear magnetic resonance and molecular dynamics simulations.
A model of the carbohydrate recognition domain of the serum form of mannose-binding protein (MBP) from rat complexed with methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside is presented. Allowed conformations for the bound sugar were derived from simulated annealing protocols incorporating distance restraints computed from transferred NOESY spectra. The resulting sugar conformations were then modeled into the MBP binding site, and these models of the complex were refined using molecular dynamics (MD) simulations in the presence of solvent water. These studies indicate that only one of the two major conformations of the alpha(1-->6) linkage found in solution is significantly populated in the bound state (omega = 60 degrees ), whereas the alpha(1-->3) linkage samples at least two states, similar to its behavior in free solution. The bound conformation allows direct hydrogen bonds to form between the sugar and K182 of MBP, in addition to other water-mediated hydrogen bonds. Estimates of binding constants of candidate complexes based on changes in solvent-accessible surface areas upon binding support the NMR and MD results. These estimates further suggest that the enthalpic gains of the additional sugar-MBP interactions in a trisaccharide as opposed to a monosaccharide are offset by entropic penalties, offering an explanation for previous binding data.


Evidence for net uptake of GABA into mouse astrocytes in primary cultures--its sodium dependence and potassium independence.
Content of GABA was measured in cultured, normal astrocytes [from the brain cortex of newborn mice] together with the effect of nonradioactive GABA on the efflux of labeled GABA from cells previously loaded with (14C)GABA. An increase of external GABA concentration from 0 to 25 micron evoked a rise of the GABA content in the cells to a level which was approximately 50 times that of the incubation medium. Neither 200 nor 2000 micron nonradioactive GABA had any effect on the rate of release of radioactivity from cells loaded with (14C)GABA. Both the high tissue/medium ratio and the lack of a GABA-induced enhancement of the release of radioactivity indicate that the previously observed high-affinity uptake of GABA in cultured astrocytes represents a net uptake and not a homoexchange with endogenous GABA. This uptake is sodium dependent but was found to be unaffected in potassium-free media; the quantitative correlation between GABA transport and sodium transport differed from that reported for synaptosomes.


D-alanine added to antipsychotics for the treatment of schizophrenia.
Hypofunction of the N-methyl-d-aspartate (NMDA) subtype glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine, glycine, endogenous full agonists of the glycine site of the NMDA receptor (NMDA-glycine site), D-cycloserine, a partial agonist, or sarcosine, a glycine transporter-1 inhibitor, improves the symptoms of schizophrenia. D-alanine is another endogenous agonist of the NMDA-glycine site that might have beneficial effects on schizophrenia. Thirty-two schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-alanine (100 mg/kg/day), which was added to their stable antipsychotic regimens. Measures of clinical efficacy and side effects were determined every other week. Patint who received D-alanine treatment revealed significant reductions in their Clinical Global Impression Scale and Positive and Negative Syndrome Scale (PANSS) total scores. The Scale for the Assessment of Negative Symptoms and PANSS subscores of positive and cognitive symptoms were improved. D-alanine was well tolerated, and no significant side effect was noted. The significant improvement with the D-alanine further supports the hypothesis of hypofunction of NMDA neurotransmission in schizophrenia and strengthens the proof of the principle that NMDA-enhancing treatment is a promising approach for the pharmacotherapy of schizophrenia.


Nitric oxide synthesis, epileptic seizures and kindling.
Nitric oxide (NO) has been implicated in synaptic changes underlying long-term potentiation and some forms of learning. It is unclear, however, whether NO contributes to long-term changes associated with the kindling of epileptic seizures. In the present study rats were treated, on the first 6 days of kindling, with L-arginine (L-Arg), the endogenous donor from which NO derives, or with L-nitro-arginine (L-No-Arg), a competitive inhibitor of NO synthesis, or with vehicle. Drugs were given in doses previously shown to affect learning or other behaviour. L-Arg (750 mg/kg IP) did not affect kindling or seizure severity. L-No-Arg (100 mg/kg) prolonged the duration of afterdischarges and convulsions on treatment days but did not advance kindling or affect seizures on subsequent days. A second experiment examined the possible role of NO in the development of resistance to seizures following prior seizures. Six or more stimuli were administered at 10-min intervals to fully-kindled rats after injection of L-No-Arg or vehicle. Vehicle-treated rats became progressively more resistant to afterdischarges and convulsions with successive stimulations but L-No-Arg-treated rats failed to do so. Rats injected with L-NO-Arg also showed an unexpected high mortality in the ensuing 24 h. L-No-Arg appeared to have no direct effect on the course of kindling but impaired the development of postictal resistance, and increased the duration and lethal after-effects of closely repeated seizures. The results do not support suggestions that antagonists of NO might prove clinically useful as anticonvulsants.


Binding of divalent cation to phosphoenzyme of sodium- and potassium-transport adenosine triphosphatase.
In order to study the action of the divalent cation which is essential for phosphorylation of sodium- and potassium-transport adenosine triphosphatase, magnesium ion, the normal ligand, was replaced with calcium ion, which had properties diffeerent from those of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, or Zn2+. Phosphorylation of the enzyme from ATP at pH 7.4 in the presence of Na+ and Ca2+ yielded a Ca.phosphoenzyme (60% of the maximal level) with a normal rate of dephosphorylation following a chase with unlabeled Ca.ATP (PK = 0.092S-1 at 0 degrees C). In contrast, after a chase by a chelator, namely ethylenediaminetetraacetic acid, 1,2-cyclohexylenedinitrilotetraacetic acid, or ethylene glycol bis-(beta-aminoethyl ether)N,N'-tetraacetic acid, dephosphorylation slowed within 5 s and half of the initial phosphoenzyme remained with a stability about 5-fold greater than normal. Three states of the phosphoenzyme were distinguished according to their relative sensitivity to ADP or to K+ added during a chase. Normally prepared Mg.phosphoenzyme was sensitive to K+ but not to ADP; Ca.phosphoenzyme was sensitive either to ADP or to K+; and the stabilized phosphoenzyme prepared from Ca.phosphoenzyme by addition of a chelator was sensitive neither to ADP nor to K+ nor to both together. Addition of Ca2+ to the stabilized phosphoenzyme restored the reactivity to that of Ca.phosphoenzyme. Addition of Mg2+ to the stabilized phosphoenzyme changed the reactivity to that of Mg.phosphoenzyme. Therefore, this unreactive, stabilized state of the phosphoenzyme appeared to be a divalent cation-free phosphoenzyme. With respect to sensitivity to ouabain, Ca.phosphoenzyme was as sensitive as Mg.phosphoenzyme but calcium-free phosphoenzyme was much less sensitive. It was concluded that the divalent cation required for phosphorylation normally remains tightly bound to the phosphoenzyme and is required for normal reactivity. Calcium ion was almost unique in dissociating relatively easily from the phosphoenzyme. Strontium ion appeared to act similarly to Ca2+.


Combined strabismus and phacoemulsification cataract surgery: a useful option in selected patients.
To evaluate the role of combined strabismus and phacoemulsification cataract extraction in patients with symptomatic cataract and strabismus. Four procedures of combined strabismus and cataract surgery are described in 3 elderly patients with strabismus of differing aetiologies. Two patients underwent one procedure; the other patient underwent two combined procedures, one to each eye. The visual acuity improved in all 3 patients. Post-operative alignment of the visual axis was achieved which allowed resolution of symptomatic diplopia in patient 1, functional binocular single vision in patient 2 and a noticeably reduced compensatory head posture in patient 3. Combined strabismus and cataract surgery is a safe procedure that can optimise visual alignment and improve visual acuity with a minimum number of operations.


Fabrication of optical chemical ammonia sensors using anodized alumina supports and sol-gel method.
In this comparative study, the fabrication and the sensing properties of various reflectometric optical ammonia gas sensors are described. In the first set of experiments the role of the support material was investigated on four different sensor membranes. Two of them were prepared by the adsorption of bromocresol green indicator on anodized aluminum plates. The applied anodizing voltages were 12 V and 24 V, which resulted in different dynamic ranges and response times for gaseous ammonia. The sol-gel method was used for the preparation of the other batch of sensors. These layers were coated on anodized aluminum plates (24 V) and on standard microscope cover glasses. In spite of the identical sensing chemistry, slightly different response times were measured merely because of the aluminum surface porosity. Gas molecules can remain entrapped in the pores, which results in delayed recovery time. On the other hand, the porous oxide film provides excellent adhesion, making the anodized aluminum an attractive support for the sol-gel layer.


Liver Fibrosis Scores and Prostate Cancer Risk and Mortality in the Atherosclerosis Risk in Communities Study.
Subclinical liver impairment due to fibrosis could influence the development and detectability of prostate cancer. To investigate the association between liver fibrosis and prostate cancer incidence and mortality, we included 5,284 men (mean age: 57.6 years, 20.1% Black) without cancer or liver disease at Visit 2 in the Atherosclerosis Risk in Communities study. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index, fibrosis 4 index (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). Over 25 years, 215 Black and 511 White men were diagnosed with prostate cancer, and 26 Black and 51 White men died from the disease. We estimated HRs for total and fatal prostate cancer using Cox regression. FIB-4 [quintile 5 vs. 1: HR = 0.47, 95% confidence interval (CI): 0.29-0.77, Ptrend = 0.004] and NFS (HR = 0.56, 95% CI: 0.33-0.97, Ptrend = 0.03) were inversely associated with prostate cancer risk in Black men. Compared with no abnormal score, men with ≥1 abnormal score had a lower prostate cancer risk if they were Black (HR = 0.46, 95% CI: 0.24-0.89), but not White (HR = 1.04, 95% CI: 0.69-1.58). Liver fibrosis scores did not appear to be associated with fatal prostate cancer in Black or White men. Among men without a clinical diagnosis of liver disease, higher liver fibrosis scores were associated with lower incidence of prostate cancer in Black men, but not in White men, and not with fatal prostate cancer in either race. Further research is needed to understand the influence of subclinical liver disease on prostate cancer development versus detectability and the racial differences observed. Investigating the link between liver fibrosis and prostate cancer risk and mortality, our study reveals the potential influence of liver health on prostate cancer development and on detection using PSA test, urging further research to understand the differential findings by race and to optimize prevention and intervention strategies.


Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions.
Melatonin is functionally involved in the control of circadian rhythm and hormonal secretion. In the present study, we investigated the roles of melatonin in the interaction of catecholamine synthesis with adrenocortical steroids by focusing on bone morphogenetic protein (BMP)-4 expressed in the adrenal medulla using rat pheochromocytoma PC12 cells. Melatonin treatment significantly reduced the mRNA expression of catecholamine synthases, including the rate-limiting enzyme tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanine decarboxylase and dopamine-β-hydroxylase expressed in PC12 cells. In accordance with changes in the expression levels of enzymes, dopamine production and cAMP synthesis determined in the culture medium and cell lysate were also suppressed by melatonin. The MT1 receptor, but not the MT2 receptor, was expressed in PC12 cells, and luzindole treatment reversed the inhibitory effect of melatonin on Th expression, suggesting that MT1 is a functional receptor for the control of catecholamine synthesis. Interestingly, melatonin enhanced the inhibitory effect of BMP-4 on Th mRNA expression in PC12 cells. Melatonin treatment accelerated BMP-4-induced phosphorylation of SMAD1/5/8 and transcription of the BMP target gene Id1. Of note, melatonin significantly upregulated Alk2 and Bmpr2 mRNA levels but suppressed inhibitory Smad6/7 expression, leading to the enhancement of SMAD1/5/8 signaling in PC12 cells, while BMP-4 did not affect Mt1 expression. Regarding the interaction with adrenocortical steroids, melatonin preferentially enhanced glucocorticoid-induced Th mRNA through upregulation of the glucocorticoid receptor and downregulation of Bmp4 expression, whereas melatonin repressed Th mRNA expression induced by aldosterone or androgen without affecting expression levels of the receptors for mineralocorticoid and androgen. Collectively, the results indicate that melatonin plays a modulatory role in catecholamine synthesis by cooperating with BMP-4 and glucocorticoid in the adrenal medulla.


Assessment by planimetry of Langerhans' cell density in penile epithelium with human papillomavirus infection: changes observed after topical treatment.
Langerhans' cells could have an important role in the immune surveillance for the malignant transformation associated with certain viral infections. A planimetric study of Langerhans' cells was performed on epithelial sheets obtained from male and female patients who presented with human papillomavirus-induced condylomata. Preliminary epidemiological studies have indicated that after a human papillomavirus infection the risk of malignant transformation is higher in the cervix than in the penis. Our study was designed in such a way that the Langerhans' cell density observed in condylomata could be compared to that detected in adjacent normal areas from the same patients. The results showed that a highly significant decrease in Langerhans' cells occurred in male and female human papillomavirus infected genital tracts. In the penis the local treatment with 5-fluorouracil restored the normal Langerhans' cell density. The significance of these findings in relationship with malignant transformation is discussed.


Ionizing diagnostic radiation exposure in patients with Crohn's disease: A retrospective study in a medium hospital and its predictive factors.
It is estimated that diagnostic medical radiation exposure may be responsable for 0.5-2% of cancers worldwide. Because of the relapsing course of Crohn's disease (CD), these patients usually requiere multiple ionizing radiation test. Stimating the total cumulative effective dose received by our CD patients and identifying the risk factors associated with the exposure to a cumulative effective dose due to the disease (CEED) > 50mSv. Retrospective cohort study (2001-2014). patients with CD. Risk dose >50mSv. For calculating de cumulative effective dose and the CEED, all the ionizing test done were taken. For identifying predictive factors for receiving a CEDD >50mSv, an univariate and a multivariate logistic regression analyses were performed using a >50mSv dose as dependent variable. Of the 267 patients analyzed the 24.6% of them received a cumulative effective dose > 50mSv and the 15.2% a CEED>50mSv. In the multivariate analysis, the following variables were identified as independent predictors associated with a CEDD >50mSv: major surgery (OR= 2.1; IC95% [1.1-3.8]; p=.019) and severity (OR= 20.6; IC95% [4.5-94.8]; p<.01). Patients with CD are more at risk of receiving risk CEED, so it would be advisable to monitor the cumulative effective dose received to anticipate our intervention in order to avoid reaching that dose. The ultrasounds and abdominal resonance enterography are alternatives in these cases, although their accessibility is limited in some centers.


MicroRNA-195 prevents hippocampal microglial/macrophage polarization towards the M1 phenotype induced by chronic brain hypoperfusion through regulating CX3CL1/CX3CR1 signaling.
Microglial polarization is a dynamic response to acute brain hypoxia induced by stroke and traumatic brain injury (TBI). However, studies on the polarization of microglia in chronic cerebral circulation insufficiency (CCCI) are limited. Our objective was to investigate the effect of CCCI on microglial polarization after chronic brain hypoperfusion (CBH) and explore the underlying molecular mechanisms. CBH model was established by bilateral common carotid artery occlusion (2-vessel occlusion, 2VO) in rats. Using the stereotaxic injection technique, lenti-pre-miR-195 and anti-miR-195 oligonucleotide fragments (lenti-pre-AMO-miR-195) were injeted into the CA1 region of the hippocampus to construct animal models with high or low expression of miR-195. Immunofluorescence staining and flow cytometry were conducted to examine the status of microglial polarization. In vitro, Transwell co-culture system was taken to investigate the role of miR-195 on neuronal-microglial communication through CX3CL1-CX3CR1 signaling. Quantitative real-time PCR was used to detect the level of miR-195 and inflammatory factors. The protein levels of CX3CL1 and CX3CR1 were evaluated by both western blot and immunofluorescence staining. CBH induced by 2VO initiated microglial/macrophage activation in the rat hippocampus from 1 week to 8 weeks, as evaluated by increased ratio of (CD68+ and CD206+)/Iba-1 immunofluorescence. And the microglial/macrophage polarization was shifted towards the M1 phenotype at 8 weeks following CBH. The expression of CX3CL1 and CX3CR1 was increased in the hippocampus of 2VO rats at 8 weeks. An in vitro study in a Transwell co-culture system demonstrated that transfection of either primary-cultured neonatal rat neurons (NRNs) or microglial BV2 cells with AMO-195-induced M1 polarization of BV2 cells and increased CX3CL1 and CX3CR1 expression and that these effects were reversed by miR-195 mimics. Furthermore, the upregulation of miR-195 induced by lenti-pre-miR-195 injection prevented microglial/macrophage polarization to M1 phenotype triggered by hippocampal injection of lenti-pre-AMO-miR-195 and 2VO surgery. Our findings conclude that downregulation of miR-195 in the hippocampus is involved in CBH-induced microglial/macrophage polarization towards M1 phenotype by governing communication between neurons and microglia through the regulation of CX3CL1 and CX3CR1 signaling. This indicates that miR-195 may provide a new strategy for clinical prevention and treatment of CBH.


The impact of resistance to methicillin in Staphylococcus aureus bacteremia on mortality.
Background: It is unclear whether methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) differ in virulence. We therefore carried out a prospective study of cases of S. aureus bacteremia over a period of 2 years at our university hospital. We report herein the results of a comparative analysis of the clinical characteristics and mortality rates associated with cases of bacteremia caused by MRSA and MSSA. Methods: Over a 2-year period, we reviewed the medical records of hospitalized patients with blood cultures positive for S. aureus. Demographic characteristics, underlying diseases, diagnosis, clinical features, severity, laboratory findings, antimicrobial treatment, and resistance to methicillin were analyzed as possible risk factors for death attributed to bacteremia. Results: The rate of mortality attributed to bacteremia was 27.3% (27 patients): 13 (43.3%) deaths were recorded for patients infected with MRSA and 14 (20.3%) for patients infected with MSSA (P=0.0339, OR=3.00 (1.08--8.46)). Two variables were significantly associated with death within 14 days of the onset of bacteremia in univariate and multivariate analyses after adjusting for antimicrobial treatment: malignant hematologic disease (protective factor; OR=0.184 (0.038--0.882)) and resistance to methicillin (risk factor; OR=2.97 (1.12--7.88)). Conclusion: This study shows that S. aureus bacteremia has a high mortality rate, especially if the strain involved is methicillin-resistant, regardless of patient age and the efficacy of antimicrobial treatment.


Altered positional regulation of nasal patency in patients with obstructive sleep apnoea syndrome.
We assessed the regulation of nasal patency supine in subjects with obstructive sleep apnoea syndrome (OSAS) compared to healthy controls. Healthy subjects increase nasal obstruction when changing body position from sitting to supine, possibly due to increased hydrostatic pressure in the head supine. Limited data indicate that this response is altered in patients with OSAS, suggesting that supine nasal patency is actively regulated. This study examined the nasal response to recumbent body position using acoustic rhinometry in OSAS patients and healthy controls. Twenty subjects (16 men and 4 women, mean age 55 +/- 16 years), with diagnosed OSAS [mean apnoea hypopnoea index (AHI) 46 +/- 22 events/h] without nasal obstruction and continuous positive airway pressure (CPAP)-naive, underwent measurement of intra-nasal cross sectional area by acoustic rhinometry at sitting and after 5 min supine. Twenty healthy controls (13 men, 7 women, mean age 35 +/- 9 years) were also included in the study. In the patients with OSAS, the mean minimal cross sectional area (MCA, left + right nasal cavity) was unchanged between sitting (1.18 +/- 0.41 cm(2)) and supine (1.21 +/- 0.35 cm(2), P = 0.5). In the healthy controls, the mean MCA decreased from 1.06 +/- 0.18 to 0.94 +/- 0.21 cm(2) supine, P = 0.01. This study showed that the normal decrease in nasal patency following a change in body position from sitting to supine is absent in patients with OSAS. The results indicate that there is an active regulation of supine nasal patency.


An exploratory randomized controlled trial comparing telephone and hospital follow-up after treatment for colorectal cancer.
Following treatment for colorectal cancer it is common practice for patients to attend hospital clinics at regular intervals for routine monitoring, although debate persists on the benefits of this approach. Nurse-led telephone follow-up is effective in meeting information and psycho-social needs in other patient groups. We explored the potential benefits of nurse-led telephone follow-up for colorectal cancer patients. Sixty-five patients were randomized to either telephone or hospital follow-up in an exploratory randomized trial. The telephone intervention was deliverable in clinical practice and acceptable to patients and health professionals. Seventy-five per cent of eligible patients agreed to randomization. High levels of satisfaction were evident in both study groups. Appointments in the hospital group were shorter (median 14.0 min, range 2.3-58.0) than appointments in the telephone group (median 28.9 min, range 6.1-48.3). Patients in the telephone arm were more likely to raise concerns during consultations. Historical approaches to follow-up unsupported by evidence of effectiveness and efficiency are not sustainable. Telephone follow-up by specialist nurses may be a feasible option. A main trial comparing hospital and telephone follow-up is justified, although consideration needs to be given to trial design and practical issues related to the availability of specialist nurses at study locations.


An information aid for newly diagnosed multiple sclerosis patients improves disease knowledge and satisfaction with care.
Patients report information deficits in the period surrounding diagnosis of multiple sclerosis (MS). We assessed the effectiveness of an add-on information aid for newly diagnosed MS patients. We randomly assigned 120 newly diagnosed MS patients from five Italian centres to diagnosis disclosure (current practice at the centre) or current practice plus information aid (ISRCTN81072971). The information aid consisted of a personal interview with a physician using a navigable compact disc and a take-home booklet. The primary composite endpoint was score in the highest tertile of MS knowledge and satisfaction with care questionnaires. Other endpoints were safety; treatment adherence; extra contacts/consultations; switching of care centre; and changes in Hospital Anxiety and Depression Scale and Control Preference Scale scores. At 1 month, 30/60 intervention and 8/60 control patients achieved the primary endpoint (odds ratio [OR] 6.5, 95% CI 2.6-16.0; p < 0.001; number needed to treat [NNT] 3). Figures at 6 months were 26/60 intervention and 11/60 control patients (OR 3.4, 95% CI 1.5-7.8; p = 0.04; NNT 4). There were no adverse events. No significant treatment effects were seen on secondary outcomes. The information aid was safe and significantly associated with attainment of the primary outcome at 1 and 6 months.


Optimising Multimodality Treatment of Resectable Oesophago-Gastric Adenocarcinoma.
Oesophago-gastric adenocarcinoma remains a leading cause of cancer-related morbidity and mortality worldwide. Although there has been an enormous progress in the multimodality management of resectable oesophago-gastric adenocarcinoma, most patients still develop a recurrent disease that eventually becomes resistant to systemic therapy. Currently, there is no global consensus on the optimal multimodality approach and there are variations in accepted standards of care, ranging from preoperative chemoradiation to perioperative chemotherapy and, more recently, adjuvant immune checkpoint inhibitors. Ongoing clinical trials are aimed to directly compare multimodal treatment options as well as the additional benefit of targeted therapies and immunotherapies. Furthermore, our understanding of the molecular and genetic features of oesophago-gastric cancer has improved significantly over the last decade and these data may help inform the best approach for the individual patient, utilising biomarker selection and precision medicine.


Spatial identification and multilevel zoning of land use functions improve sustainable regional management: a case study of the Yangtze River Economic Belt, China.
The quantitative identification and zoning management of land use functions (LUFs) are important starting points for solving the problems of resource allocation and sustainable development. In this study, with the Yangtze River Economic Belt (YREB) as the case study area, LUFs were grouped into three primary categories: economic function (ENF), social function (SCF), and ecological function (ELF). The least square error model was adopted to identify the morphological changes of LUFs. A two-dimensional discriminant matrix of the dynamic degree of LUF change and terrain niche index was constructed to explain the terrain gradient effect of LUFs. Bivariate local spatial autocorrelation was used to analyze the trade-offs in 2018 between ELF and ENF, and ELF and SCF. Finally, a new multilevel zoning scheme for LUFs was proposed. The results showed that from 1990 to 2018, ENF increased rapidly in cities along the Yangtze River, the overall level of SCF declined, and ELF in the south of the Yangtze River was better than that in the north. LUFs' morphological zoning exhibited significant regional differences. SCF-ELF combination areas and ELF dominance areas were mainly optimized in the second-level zoning. The areas with weak ELF were concentrated in the east of the YREB. Based on these results, nine kinds of LUF zonings and six kinds of major functional zonings were devised, and policy allocation was arranged for each zoning to improve the efficiency of spatial zoning management. Our research provides a reference for large-scale regional sustainable development and land use zoning management.


Cortical function and sensorimotor plasticity are prognostic factors associated with future low back pain after an acute episode: the Understanding persistent Pain Where it ResiDes prospective cohort study.
Predicting the development of chronic low back pain (LBP) at the time of an acute episode remains challenging. The Understanding persistent Pain Where it ResiDes study aimed to identify neurobiological and psychological risk factors for chronic LBP. Individuals with acute LBP (N = 120) participated in a prospective cohort study with 6-month follow-up. Candidate predictors were selected from the neurobiological (eg, sensorimotor cortical excitability assessed by sensory and motor-evoked potentials and brain-derived neurotrophic factor genotype), psychological (eg, depression and anxiety), symptom-related (eg, LBP history), and demographic domains. Analyses involved multivariable linear regression models with pain intensity or disability degree as continuous variables. Secondary analyses involved a multivariable logistic model with the presence of LBP at 6 months (thresholding pain intensity and disability degree) as a dichotomous variable. Lower sensory cortex and corticomotor excitability, higher baseline pain intensity, higher depression, stress, and pain catastrophizing were the strongest predictors ( R2 = 0.47) of pain intensity at 6 months. Older age and higher pain catastrophizing were the strongest predictors ( R2 = 0.30) of disability at 6 months. When the LBP outcome was dichotomised, sensory cortex and corticomotor excitability, brain-derived neurotrophic factor genotype, depression and anxiety, LBP history and baseline pain intensity, discriminated between those who did and did not report LBP at 6 months (C-statistic 0.91). This study identifies novel risk factors for the development of future LBP. Neurobiological risk factors, when added to a multivariable linear regression model, explained a further 15% of the variance in the 6-month pain intensity.


Gender differences in health indicators by longest-held occupation and industry of longest employment.
As more women enter the work force, they may increasingly come into contact with occupational and industrial hazards. The distribution of longest-held occupation and industry of longest employment and selected health indicators are presented for US men and women. These data are based on the National Center for Health Statistics' 1980 National Health Interview Survey, the first survey to collect data on longest-held, in addition to current, occupation and industry of employment. Data on limitation of activity, disability days, and physician and dentist visits are presented by categories of longest-held occupation and industry of longest employment. Overall, more men than women (except for younger female farm laborers and farm foremen) reported a limitation of activity due to chronic conditions; however, more women reported days of restricted activity. Female private household workers reported over a month of restricted activity. This study suggests the need to further investigate more direct health measures of female farm and agriculture workers and female private household workers.


Cellular Immune Responses in Lymphoid Tissues of Broiler Chickens Experimentally Infected with Necrotic Enteritis-Producing Clostridium perfringens Strains.
Host cellular responses against Clostridium perfringens (CP), the causative agent of necrotic enteritis (NE) in chickens, are poorly understood. In the present study, we first tested the NE-producing ability of seven netB+ CP strains (CP5, CP18, CP26, CP64, CP67, CP68, and NCNE-1), using an experimental infection model of broiler chickens. Evaluation of intestinal gross lesions showed that all the strains, except CP5, were able to produce NE, while CP26 and CP64 strains produced relatively more severe lesions when compared with other groups. Next, cellular responses in the cecal tonsil (CT), bursa of Fabricius, and spleen were evaluated in chickens infected with strains representing variation in the level of virulence, namely, avirulent CP5, virulent CP18, and a relatively more virulent CP26 strain. Immunophenotyping analysis showed that CT or splenic macrophage frequencies were significantly higher in CP18- and CP26-infected chickens compared with uninfected controls, while the frequencies of γδ T-cells and B-cells in the CT of CP26-infected chickens were significantly higher than those in the uninfected, CP5- or CP18-infected groups. The T-cell analysis showed that chickens infected with CP18 and CP26 had a significantly higher number of splenic CD4+ and CD8+ T-cells expressing CD44 and CD28 activation molecules, while CP26-infected chickens also had significantly increased CT frequency of these activated CD4+ and CD8+ T-cells when compared with uninfected or CP5-infected groups. Collectively, our findings suggested that cellular responses, including activation of T-cells, are selectively induced against virulent CP strains and that the NE-producing characteristics of this pathogen may influence the outcome of immunity to NE.


Enhanced IMC based PID controller design for non-minimum phase (NMP) integrating processes with time delays.
Internal model control (IMC) with optimal H2 minimization framework is proposed in this paper for design of proportional-integral-derivative (PID) controllers. The controller design is addressed for integrating and double integrating time delay processes with right half plane (RHP) zeros. Blaschke product is used to derive the optimal controller. There is a single adjustable closed loop tuning parameter for controller design. Systematic guidelines are provided for selection of this tuning parameter based on maximum sensitivity. Simulation studies have been carried out on various integrating time delay processes to show the advantages of the proposed method. The proposed controller provides enhanced closed loop performances when compared to recently reported methods in the literature. Quantitative comparative analysis has been carried out using the performance indices, Integral Absolute Error (IAE) and Total Variation (TV).


Biogenic Volatile Organic Compounds Emission of Brazilian Atlantic Tree Grown Under Elevated Ozone in Ambient Controlled and Field Conditions.
Croton floribundus (L.) Spreng trees were exposed to accumulated ozone (O3) levels under laboratory and field conditions and monitored the foliar visible symptoms and BVOC emissions. Plants exposed to O3 in the laboratory presented more substantial damage and significant increase in the BVOC emissions than plants in the field. Caryophyllene and 3-hexen-1-ol emissions were significantly increased in plants exposed to O3 in the laboratory. Under field conditions, methyl salicylate (MeSA) was the majority compound emitted. A positive correlation among the meteorological conditions, O3 and MeSA emission was observed in the field conditions, which may represent a mechanism of tolerance by C. floribundus to deal with long-term exposure to O3.


Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations.
Recombinant human interferon gamma used for treatment of psoriatic arthritis was found to induce expression of HLA-DR, but not HLA-DP or HLA-DQ, on keratinocytes at the site of injection. Some patients showed an improvement of their joint symptoms, but the cutaneous manifestations remained unaffected. In 10 of 42 patients, punctiform psoriatic foci could be induced at the site of injection of interferon gamma. For this presentation, we selected a female patient with psoriatic arthropathy and type II diabetes mellitus in whom psoriasis was induced at the site of application of interferon gamma, but not after subcutaneous injection of insulin or placebo. We conclude that interferon gamma is an important lymphokine in the development of psoriasis.


The Replication Checkpoint Prevents Two Types of Fork Collapse without Regulating Replisome Stability.
The ATR replication checkpoint ensures that stalled forks remain stable when replisome movement is impeded. Using an improved iPOND protocol combined with SILAC mass spectrometry, we characterized human replisome dynamics in response to fork stalling. Our data provide a quantitative picture of the replisome and replication stress response proteomes in 32 experimental conditions. Importantly, rather than stabilize the replisome, the checkpoint prevents two distinct types of fork collapse. Unsupervised hierarchical clustering of protein abundance on nascent DNA is sufficient to identify protein complexes and place newly identified replisome-associated proteins into functional pathways. As an example, we demonstrate that ZNF644 complexes with the G9a/GLP methyltransferase at replication forks and is needed to prevent replication-associated DNA damage. Our data reveal how the replication checkpoint preserves genome integrity, provide insights into the mechanism of action of ATR inhibitors, and will be a useful resource for replication, DNA repair, and chromatin investigators.


Sudden Transition between Classical to Quantum Decoherence in bipartite correlated Qutrit Systems.
Classical to quantum decoherence transition, an issue existing for incoherent superposition of Bell-diagonal states is studied for three dimensional bipartite AB mixed quantum systems. Depending on the initial conditions, the dynamics of classical and quantum correlations can exhibit a sudden transition between classical to quantum decoherence. This result is calculated numerically by using entropic and geometric measures of correlations. An alternative explanation for this effect could be obtained by extending the bipartite A ⊗ B qutrit system to a pure tripartite A ⊗ B ⊗ C system. The freezing of classical correlations in AB is related to a freezing of the entanglement in the AC bipartition.


[Unwanted pregnancy as conflict. Potential for developmental steps?].
Problems of pregnancy-conflicts are presented from the point of view of counselors of the family planning service at the university clinic for obstetrics and gynecology in Bern. By means of case examples and a literature review, the possible backgrounds of undesired pregnancies are elucidated.


Determination of slime-producing S. epidermidis specific antibodies in human immunoglobulin preparations and blood sera by an enzyme immunoassay: correlation of antibody titers with opsonic activity and application to preterm neonates.
Slime-producing Staphylococcus epidermidis is responsible for severe infections in immunocompromised patients and, particularly, in premature infants who are transiently deficient in IgG. A sulfated polysaccharide with molecular mass of 20-kDa (20-kDa PS) has been recognized as the major polysaccharide component and antigenic determinant of S. epidermidis extracellular slime layer. The presence of adequate amounts of antibodies to 20-kDa PS in patients' sera would be of importance to prevent or treat slime-producing S. epidermidis bacteremia. Administration of intravenous immunoglobulin (IVIG) is considered to be a reasonable IgG replacement therapy and has been widely used to prevent or treat neonatal sepsis. Clinical trials have shown conflicting results on the efficacy of IVIGs and this phenomenon has been attributed to the variability of IVIG preparations in the content and opsonic activity of IgG against microorganisms of clinical importance. Monitoring of antibodies to distinct bacterial macromolecules, which are species-specific and responsible for bacterial infections, has not been performed previously. A highly precise and repeatable enzyme immunoassay was developed to determine quantitatively the levels of antibodies against the 20-kDa PS of S. epidermidis slime. The amount of 20-kDa PS specific antibodies found in 27 lots of an IVIG preparation (Sandoglobulin) correlated well with their in vitro opsonic activity against slime-producing S. epidermidis. The majority of lots (75%) having titers higher than 200 units/ml showed significant opsonic activity (50-75%) towards slime-producing S. epidermidis. Sandoglobulin lots with titers higher than 200 units/ml of 20-kDa PS specific IgG were administered as a prophylactic agent to low-birth weight (lower than 1700 g) preterm neonates immediately after birth. The levels of total and 20-kDa PS specific IgG in neonates' blood sera were significantly higher than those found in the control group, even 10 days after the last infusion. The rate of slime-producing S. epidermidis bacteremia in neonates who received IVIG was also considerably lower than those in the control group. The results of this study suggest that specific IgG titers estimated by the developed enzyme immunoassay may well be indicative of the IVIG opsonic activity against slime-producing S. epidermidis. Furthermore, administration of Sandoglobulin with titers higher than a cut-off value of 200 units/ml may significantly protect preterm neonates against slime-producing S. epidermidis bacteremia.


Methylation of free-floating deoxyribonucleic acid fragments in the bronchoalveolar lavage fluid of dogs with chronic bronchitis exposed to environmental tobacco smoke.
The etiology of canine chronic bronchitis (CB) is not completely understood, although exposure to environmental tobacco smoke (ETS) affects the airway inflammatory responses in some dogs with CB. The mechanism by which this occurs is unknown. We investigated the concentrations and methylation rates of free-floating DNA fragments in bronchoalveolar lavage fluid (BALF) from dogs with chronic bronchitis. Based on serum cotinine levels, dogs with CB were divided into 2 groups: dogs that either had or had not been exposed to ETS. Our results demonstrated that the total nucleated cell and macrophage numbers increased in BALF of ETS-exposed dogs with CB. There were no significant differences in DNA concentrations and methylation rates in BALF between the 2 groups. However, 3 out of 8 dogs exposed to ETS had high DNA methylation rates in their BALF samples. Our results suggest that ETS exposure leads to epigenetic modifications of cellular components in BALF in dogs diagnosed with CB.


Identification of a diacylglycerol acyltransferase 2 gene involved in pheromone biosynthesis activating neuropeptide stimulated pheromone production in Bombyx mori.
Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triacylglycerol biosynthesis. In the present study, a DGAT2 gene from Bombyx mori was characterized. Temporal expression profiles indicated that BmDGAT2 steadily increased from 96 h before eclosion (-96 h) to an expression peak in the pheromone glands (PGs) of new-emerged female (0 h), a key stage for sex pheromone production. Spatial expression analysis revealed that the BmDGAT2 transcript was most richly expressed in PGs. Decapitation and subsequent methoprene, a juvenile hormone (JH) analog, treatment experiments revealed that JH had no influence on the expression of BmDGAT2 transcript before emergence, but inhibited the expression of BmDGAT2 transcript when administered to newly emerged adults. Further RNAi analysis confirmed that the decrease in BmDGAT2 mRNA level caused a significant reduction in sex pheromone production. Thus, DGAT2 is a key enzyme regulating B. mori sex pheromone synthesis and release.


Special Issue "Genetics and Epigenetics of Neuromuscular Diseases".
Neuromuscular disorders (NMDs) include several hereditary or acquired conditions that impair the neuromuscular system and muscle function [...].