Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies.
To assess the pharmacokinetics and pharmacodynamics of levonorgestrel intrauterine system (LNG-IUS) 13.5 mg and LNG-IUS 19.5 mg (total content). Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III studies. Randomized, open-label, multicenter studies. Nulliparous and parous women. Levonorgestrel intrauterine system 13.5 mg, LNG-IUS 19.5 mg, or LNG-IUS 20 μg/24 h (total content 52 mg). Pharmacokinetics of LNG, ovulation rate, cervical function, and endometrium effects. The in vivo LNG release rate of LNG-IUS 13.5 mg was approximately 14 μg/24 h after 24 days, declining progressively to 5 μg/24 h after 3 years. The average LNG serum concentration over 3 years of use was 74.3 ng/L, 114 ng/L, and 218 ng/L for LNG-IUS 13.5 mg, LNG-IUS 19.5 mg, and LNG-IUS 20 μg/24 h, respectively. All treatments showed very similar progestogenic effects on cervical mucus, with low and similar cervical scores throughout treatment. Ovulation was observed in the majority of women in all groups where assessment was possible, although there was a lower incidence of anovulation with LNG-IUS 13.5 mg and LNG-IUS 19.5 mg compared with LNG-IUS 20 μg/24 h. The progestogenic effect on the endometrium was marked in all three LNG-IUS groups. Levonorgestrel intrauterine system 13.5 mg and LNG-IUS 19.5 mg result in alower systemic exposure to LNG, lower incidence of anovulation, and similar progestin impact on the endometrium and cervical function compared with LNG-IUS 20 μg/24 h.


Partial biochemical characterisation of collagen in carious dentin of human primary teeth.
The process of dentin caries is a complex event involving demineralisation and matrix degradation. The objective of this study was to biochemically characterise collagen, the major dentin matrix component, by amino acid and cross-link analyses in two distinct carious dentin regions of human primary teeth. Twenty-seven carious primary teeth were obtained from 3 to 11-year-old patients and three layers of dentin, i.e. outer, inner carious dentin and normal dentin, were identified by a 1% acid red solution and dissected from each tooth. The samples were pulverised, the respective layers obtained from three to five teeth were pooled and six samples per layer were analysed. Aliquots of the dried dentin powder were hydrolysed with 6N HCl at 110 degrees C for 24h and subjected to amino acid analyses. Other aliquots were demineralised, reduced with standardised NaB3H4, hydrolysed and subjected to quantitative collagen cross-link analyses. The results demonstrated that in the outer carious layer the collagen-associated amino acids were significantly lower and the reducible cross-links were markedly diminished when compared to the other two groups. There was no significant difference in these parameters between the inner carious and the normal layers. The data indicate that while the collagen in the outer carious dentin is significantly altered and degraded, the one in the inner carious dentin is relatively unaffected in primary teeth.


[Association of disseminated nocardiosis and Kaposi's sarcoma after kidney transplantation].
We report a 40-year-old kidney recipient who developed disseminated nocardiosis associated with cutaneous Kaposi's sarcoma. The withdrawal of immunosuppressive therapy and prolonged antibiotic therapy, including imipenem and trimethoprim-sulfamethoxazole, resulted in a favourable outcome of both disorders. Three years later, graft function remains stable with a complete regression of skin and pulmonary abnormalities. This case report illustrates the predisposing role of immunosuppressive treatment in the occurrence of infectious and neoplastic complications observed after solid-organ transplantation.


Quality of reporting of descriptive studies in implant dentistry. Critical aspects in design, outcome assessment and clinical relevance.
The aim of this study was to conduct a review on quality of reporting on descriptive studies in implant dentistry using the STROBE Statement and to analyse possible changes in quality of reporting on descriptive studies in implant dentistry over time. A hand search to select descriptive studies was carried out in seven dental journals, which were thought to have interest in the field of dental implants. Issues of the years 1990, 1995, 2000, 2005 and 2010 were screened. The STROBE Statement with 22 criteria to match was used to determine the quality of an article. Totally 4657 titles and abstracts were screened; 260 of them were found to be reporting on a descriptive study. Percentages of properly addressed items were 46% in 1990, 56% in 1995, 54% in 2000, 59% in 2005 and 70% in 2010. From this review can be concluded that quality of reporting on descriptive studies in implant dentistry is low; there is some improvement from 1990 to 2010, but it does not exceed 70% coverage of the possible to address items.


Remdesivir in Solid Organ Recipients for COVID-19 Pneumonia.
Solid organ transplant (SOT) recipients represent a vulnerable patient population and are of high risk for airborne viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Treatment of COVID-19 is still challenging, as no proven therapeutic regimen is available for immunocompromised patients. Our aim was to evaluate the efficacy and safety of remdesivir (RDV) therapy in infected hospitalized SOT patients. All transplanted recipients (N = 25; lung: 19; kidney: 3, liver: 2, heart: 1) who needed hospital care were reviewed in the time period between September 2020 and May 2021 out of the 945 patients treated at the Department. Case control matched patients receiving RDV (all in need of supplementary oxygen) and standard of care (SOC) were included as controls. Among the 25 SOT patients (female:male = 11:14; average age = 53.2 ± 12.7 years), 15 received RDV medication (RDV-TX), and in 10 cases SOC treatment was used (SOC-TX). Significantly worse clinical score was noted in RDV patients compared with RDV-TX; however, transfer to a higher intensity care unit as well as 60-day survival of RDV-TX patients were significantly worse. All SOT fatalities within 60 days of follow-up were lung transplant recipients (6 out of 19 lung transplant patients). No adverse events were noted related to RDV therapy. In SOT patients, especially lung transplant recipients, with severe COVID-19 needing supplementary oxygen, RDV treatment was safe; however, outcome was significantly worse as compared with nontransplanted individuals with initially worse clinical parameters.


Erratum: The History of Biomechanics in Total Hip Arthroplasty.
[This corrects the article on p. 359 in vol. 51, PMID: 28790464.].


An assessment of preoperative coagulation screening for tonsillectomy and adenoidectomy.
Preoperative coagulation studies are commonly employed in order to try to identify the 2-4% of all patients undergoing tonsillectomy/adenoidectomy surgery who experience hemorrhagic complications. In an atmosphere of increasing cost consciousness, evaluation of the efficacy of screening tests is warranted. The records of 994 out of 1050 patients consecutively scheduled for tonsillectomy, adenoidectomy or T&A over a 2.5-year period were retrospectively reviewed in order to determine the usefulness of partial thromboplastin (PTT) and prothrombin time (PT) screening in predicting surgical and postsurgical bleeding. For patients with no history or clinical signs indicating possible bleeding disorder, preoperative PT and PTT failed to predict bleeding as an outcome. Also no patients were identified in this series to have previously undiagnosed coagulopathies on the basis of screening PT/PTT. The purpose of any screening test is to identify disease early enough for therapeutic intervention to be effective. Although preoperative PT/PTT will occasionally identify an unsuspected von Willebrand's or other coagulopathy, the prevalence of bleeding disorders in patients with negative history and examination is low enough that PT/PTT has essentially a zero predictive value for surgical bleeding. Screening PT/PTT should therefore be reserved for patients with known or suspected coagulopathies.


Psychotropics regulate Skp1a, Aldh1a1, and Hspa8 transcription--potential to delay Parkinson's disease.
Recently, the genes p19 S-phase kinase-associated protein 1A (SKP1), huntingtin interacting protein-2 (UBE2K), aldehyde dehydrogenase family 1 subfamily A1 (ALDH1A1), 19 S proteasomal protein PSMC4, and heat shock 70-kDa protein 8 (HSPA8) have been found to predict the onset and progression of Parkinson's disease (PD). These findings prompted a review of the effects of commonly prescribed psychiatric medicines, drugs that are used in treating PD, on the expression of these genes. Findings in the published medical literature were reviewed and gene expression data in the Gene Expression Omnibus Profiles database were analyzed. The results indicate that fluoxetine upregulated the risk-attenuating genes Skp1a and Aldh1a1 and olanzapine downregulated risk-enhancing Hspa8 while also downregulating Aldh1a1. Less conclusive evidence suggested that fluoxetine might also downregulate Hspa8 and clozapine might downregulate risk-enhancing Ube2k, but that olanzapine might upregulate Ube2k. Together, the present findings suggest that these psychotropics may delay PD onset (fluoxetine, olanzapine, and perhaps clozapine) and progression (fluoxetine, clozapine, and perhaps olanzapine). These gene expression findings should be replicated by RT-PCR studies in humans and, if confirmed, these drugs should then be studied in animal models and PD patients.


Tissue zinc dynamics during the immune reaction in mice.
Owing to the importance of zinc for the functioning of the immune system, the role of endogenous Zn, located both in lymphoid and nonlymphoid organs, was investigated during the standard humoral and cellular types of immune response. For this purpose, the dynamics of hepatic, thymic, splenic, and renal Zn content was determined in mice sensitized with (a) sheep red blood cells and (b) semiallogeneic lymphocytes during the local host vs graft reaction (HVGR). The data obtained by ion-coupled plasma spectrometry revealed that the humoral type of immunity is characterized by a significant increase of Zn concentration in the liver and in the thymus. Simultaneously, linear regression analysis showed that the generation of plaque-forming cells in the individual mouse was highly positively correlated with Zn concentration in the liver (r=0.897), and spleen (r=0.833), and negatively with Zn concentration in the thymus (r=-0.624). Similar relationships between the intensity of local immune reaction and tissue Zn levels were found in local HVGR at the fifth day in the liver and spleen (r=0.861 and r=0.695, respectively), at the seventh day in the thymus (r=-0.797), and at the tenth day in the liver (r=-0.859). The data emphasize the necessity of Zn for the development of normal immune response and point to the existence of a Zn-dependent hepato-thymic axis during the humoral and cellular types of immune reactivity.


Flapless Versus Traditional Dental Implant Surgery: Long-Term Evaluation of Crestal Bone Resorption.
The literature reports that flapless compared with traditional implant surgery can be associated with several advantages, including the maintenance of peri-implant hard tissues. This study investigated vertical bone resorption during long-term follow-up after implant placement with flapless versus traditional surgery. In this prospective, randomized controlled clinical trial, 40 patients underwent implant placement at the Maxillofacial Department Surgery of the Istituto Stomatologico Italiano Hospital in Milan, Italy. Patients were randomly assigned to the control or experimental group. The control group had implants placed with open flap surgery (traditional surgery), whereas the experimental group had implants placed with flapless surgery. The distance between the first implant thread and the marginal crestal bone level was measured at the basal, loading, and long-term control points. The basal recording was performed just after implant placement. The loading measurement was recorded at the time of implant loading, after 2 months of healing for the lower jaw and after 3 months of healing for the upper jaw, and the long-term control record was registered 36 months after implant placement. Statistical analysis was performed using mean values and standard deviations based on bone resorption in the 2 groups. To detect statistical differences, the Student t test was applied. Differences were considered significant if P values were less than .05. The control group (open flap surgery) was comprised of 19 patients, and the experimental group (flapless surgery) was comprised of 21 patients. No statistical differences were found in peri-implant bone resorption between the 2 groups at the basal, implant loading, and 3-year control recordings. According to this study, the approach to implant surgery does not seem to influence peri-implant bone resorption in humans, at least for the period measured in this study.


Long-term outcomes of anterior dual-rod instrumentation for thoracolumbar and lumbar curves in adolescent idiopathic scoliosis: a twelve to twenty-three-year follow-up study.
Anterior spinal fusion with instrumentation is used for the treatment of thoracolumbar/lumbar scoliosis. The aim of this long-term, retrospective, hospital-based cohort study was to determine the outcomes of anterior dual-rod instrumentation in a consecutive series of patients with thoracolumbar/lumbar adolescent idiopathic scoliosis managed by a single surgeon at a single institution. A consecutive series of thirty-two patients with Lenke type-5C thoracolumbar/lumbar adolescent idiopathic scoliosis were included. Outcome measures included patient demographics, radiographic measurements, adjacent-segment degeneration, pulmonary function, and Scoliosis Research Society outcome instrument (SRS-30) scores. Perioperative and postoperative complications were recorded. Thirty patients were followed for a mean of 17.2 years (range, twelve to twenty-three years). The mean thoracolumbar/lumbar Cobb angle correction rate and correction loss at the time of the latest follow-up were 79.8% and 3.4°, respectively. The average percent-predicted forced vital capacity and forced expiratory volume in one second were 91.8% and 81.8%, respectively. The average total SRS-30 score was 4.2. Mild degeneration below the fusion mass was observed in 23% of the patients. No instrumentation failure, pseudarthrosis, surgical site infection, or clinically relevant neurovascular complications were observed. Two patients required surgical revision with posterior spinal instrumentation, one because of subjacent disc wedging and the other because of progression of the thoracic curve deformity. Radiographic findings, pulmonary function, and clinical measures were satisfactory at the time of follow-up, at a minimum of twelve years. Anterior dual-rod instrumentation remains a useful surgical treatment for Lenke type-5C thoracolumbar/lumbar adolescent idiopathic scoliosis.


Impacts of typical pharmaceuticals and personal care products on the performance and microbial community of a sponge-based moving bed biofilm reactor.
Four lab-scale moving bed biofilm reactors (MBBRs) were built to treat simulated wastewater containing typical pharmaceuticals and personal care products (PPCPs). The efficiency in removing different PPCPs at different concentrations (1, 2 and 5 mg/L) and their effects on the performance of MBBRs were investigated. Results showed that the average removal efficiencies of sulfadiazine, ibuprofen and carbamazepine were 61.1 ± 8.8%, 74.9 ± 8.8% and 28.3 ± 7.4%, respectively. Compared to the reactor without PPCPs, the total nitrogen (TN) removal efficiency of the reactors containing sulfadiazine, ibuprofen and carbamazepine declined by 21%, 30% and 42%, respectively. Based on the microbial community analysis, increasing the PPCPs concentration within a certain range (<2 mg/L) could stimulate microbial growth and increase microbial diversity yet the diversity reduced when the concentration (5 mg/L) exceeded the tolerance of microorganisms. Furthermore the presence and degradation of different PPCPs resulted in a different kind of microbial community structure in the MBBRs.


Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses.
Suppressor of cytokine signaling (SOCS) proteins serve as negative regulators of cytokine receptor signaling. However, SOCS proteins are not only induced via the JAK/STAT pathway, but are also transcribed on triggering of pattern recognition receptors such as TLRs. We now show that SOCS1 can also be induced by the non-TLR pattern recognition receptor Dectin-1 in murine bone marrow-derived dendritic cells and macrophages (BMMs). The C-type lectin Dectin-1 binds to yeasts and signals either in an autonomous manner or can be triggered in combination with TLRs. In our study, SOCS1 was expressed independently of any TLR engagement as a direct target gene of the Dectin-1 ligand Zymosan. Induction of SOCS1 was mediated by a novel pathway encompassing the tyrosine kinases Src and Syk that activated the downstream kinase proline-rich tyrosine kinase 2. Proline-rich tyrosine kinase 2, in turn, caused activation of the MAPK ERK, thereby triggering SOCS1 induction. SOCS1 did not modulate Dectin-1 signaling but affected TLR signaling, leading to decreased and abbreviated NF-κB activation in BMMs triggered by TLR9. Furthermore, IL-12 and IL-10 secretion were inhibited by SOCS1. We additionally observed that IL-17-producing Th cells were clearly increased by SOCS1 in BMMs. Our results show that SOCS1 is expressed via a new, NF-κB-independent pathway in Dectin-1-triggered murine BMMs and influences TLR cross talk and T cell priming.


Phosphoinositide lipid second messengers: new paradigms for calcium channel modulation.
Neuronal Ca2+ channels are key transducers coupling excitability to cellular function. As such, they are tightly regulated by multiple G protein-signaling pathways that finely tune their activity. In addition to fast, direct G(beta)gamma modulation of Ca2+ channels, a slower Galpha(q/11)-mediated mechanism has remained enigmatic despite intensive study. Recent work suggests that membrane phosphoinositides are crucial determinants of Ca2+ channel activity. Here, we discuss their role in Ca2+ channel modulation and the leading theories that seek to elucidate the underlying molecular details of the so-called "mysterious" G(q/11)-mediated signal.


Hemibody irradiation. An effective second-line therapy in drug-resistance multiple myeloma.
The authors report the results of treatment of 41 patients with melphalan-resistant multiple myeloma using single half-body irradiation (HBI) or double half-body irradiation (DHBI). Patients were grouped using prognostic classification reported by the Medical Research Council. Patients in group I and II showed the best response to therapy with reduction in serum of urinary paraprotein and improvement in symptoms, most notably a marked reduction in bone pain. In these groups five patients have survived over 2 years after therapy. The therapeutic response appeared better in those patients who received DHBI as opposed to those whom treated with single HBI. Patients in group III did not achieve prolonged survival but effective relief of bone pain was a consistent finding in these patients also. Thus HBI represents an alternative to combination chemotherapy as second-line treatment of patients with melphalan-resistant multiple myeloma. A comparative study of HBI versus combination chemotherapy is now indicated to establish which therapeutic approach is most effective.


Leaf carbon isotope ratios of plants from a subtropical monsoon forest.
Carbon isotope ratios were used to survey the distribution of photosynthetic pathways among taxa, the relationship between photosynthetic pathway and habitat light levels, and the relationship between intercellular CO2 levels of C3 plants and habitat light levels within a subtropical monsoon forest in southern China. Of 128 species, most (94) possessed the C3 photosynthetic pathway; 33 species possessed the C4 pathway and all of these were restricted to high light locations. There was one epiphytic CAM species. The C3 species were classified as occurring in open, intermediate, and closed canopy sites. Among C3 species, carbon isotope ratios tended to become more negative with decreasing light availability in the habitat.


Comparison of radiation regimens in the treatment of Glioblastoma multiforme: results from a single institution.
The optimal fractionation schedule of radiotherapy (RT) for Glioblastoma multiforme (GBM) is yet to be determined. We aim to compare different fractionation regimens and identify prognostic factors to better tailor RT for newly diagnosed GBM patients. All data for patients who underwent surgery for GBM between January 2005 and December 2012 were compiled. Clinical information was collected using patient charts and government registry. Cox analysis was used to identify variables affecting survival and treatment outcome. The median follow-up time was 13.2 months. Two hundred and seventy-six patients met the inclusion criteria, including 147 patients in the 60 Gy in 30 fractions (ConvRT) group, 86 patients in the 60 Gy in 20 fractions (HF60) group, and 43 patients in the 40 Gy in 15 fractions (HF40) group. Median survival (MS) was 16.0 months with a median progression-free survival (PFS) of 9.23 months in the ConvRT group. This was comparable to outcome in the HF60 group with MS 15.0 months and a median PFS of 9.1 months. Patients in the HF40 group had MS of 8 months, with a median PFS 5.4 months. Cox analysis showed no significant difference in OS between the ConvRT and HF60 groups but worse outcome in the HF40 group (HR 2.22, P=0.04). MGMT methylation, extent of resection, use of chemotherapy, and repeat surgery were found to be significant independent prognostic factors for survival. HF60 constitutes a safe RT approach that shows survival comparable to standard RT while allowing for a shorter treatment time.


Posterior Spinal Fusion for Severe Spinal Deformities in Musculocontractural Ehlers-Danlos Syndrome: Detailed Observation of a Novel Case and Review of 2 Reported Cases.
Musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14) is a recently delineated connective tissue disorder characterized by multisystem congenital malformations and progressive connective tissue fragility-related manifestations. With only 2 cases of mcEDS-CHST14 containing precise information on surgical spinal correction being reported to date, there remains no consensus on treatment standards. This study describes the detailed clinical and radiologic outcomes of the third known patient with mcEDS-CHST14 who successfully underwent surgery for severe kyphoscoliosis. The patient was a 19-year-old girl with mcEDS-CHST14 who suffered from low back pain and decreased daily activities caused by progressive kyphoscoliosis. She underwent posterior spinal fusion with an all-pedicle screw construct from T4 to L4 for a preoperative main curve Cobb angle of 69 degrees and kyphotic angle of 27 degrees. Postoperative Cobb angle of the main curve and kyphotic angle were 26 and 6 degrees, respectively. Although sufficient correction was achieved without disseminated intravascular coagulation or other serious sequelae, a large amount of blood (2600 g) was lost due to tissue fragility. Her low back pain was decreased at 1 year after surgery. On the basis of the present and 2 earlier reported cases, posterior spinal fusion may be a reasonable surgical option for severe progressive spinal deformities in patients with mcEDS-CHST14. However, careful attention is needed for possible massive blood loss from tissue fragility.


Evaluation of methods for detection of anticentromere antibodies and other antinuclear antibodies.
Our immunologic studies of twenty-five patients with acrosclerosis with severe acral involvement, twenty-seven patients with most or all of the signs of CREST syndrome, twenty-two patients with systemic lupus erythematosus as positive controls, and ninety-one blood donors as negative controls centered on an evaluation of eight antigenic substrates, including four types of human cells for the detection of anticentromere antibodies (ACA) and other antinuclear antibodies (ANA). The ACA, which occurred only among the patients with most or all of the signs of CREST syndrome, could be detected reliably on human cell lines HEp-2 and KB but not on a mouse cell line or on the three types of tissue sections examined. Comparisons of human HEp-2 and KB cell lines from four sources indicated that HEp-2 cells are the best of the substrates tested for detection of ACA. Since rodent tissue sections give negative reactions with ACA, they are indicated for confirmation. In general, results varied with the type and source of antigen used. Thus ANA findings need to be expressed not only in terms of the titers of the antibodies and the pattern(s) of their reactions but also in terms of the type of antigen or substrate used, its source, and the diagnostic significance of findings in the given test system.


Association between baseline peri-infarct magnetic resonance spectroscopy and regional white matter atrophy after stroke.
Cerebral atrophy after stroke is associated with poor functional outcome. The prediction and prevention of post-stroke brain atrophy could therefore represent a target for neurorestorative therapies. We investigated the associations between peri-infarct metabolite concentrations measured by quantitative MRS and brain volume change in the infarct hemisphere after stroke. Twenty patients with ischemic stroke were enrolled. Patients underwent 3T-MRI within 1 week of onset, and at 1 and 3 months. At the baseline scan, an MRS voxel was placed manually in the peri-infarct area and another in the corresponding contralateral region. Volumetric analysis of T1 images was performed using two automated processing packages. Changes in gray and white matter volume were assessed as percentage change between 1 and 3 months. Mean concentrations (institutional units) of N-acetylaspartic acid (NAA) (6.1 vs 7.0, p = 0.039), total creatine (Cr+PCr) (5.4 vs 5.8, p = 0.043), and inositol (4.5 vs 5.0, p = 0.014), were significantly lower in the peri-infarct region compared with the contralateral hemisphere. There was a significant correlation between baseline peri-infarct NAA and white matter volume change in the infarct hemisphere between 1 and 3 months, with lower NAA being associated with subsequent white matter atrophy (Spearman's rho = 0.66, p = 0.010). The baseline concentration of Cr+PCr was also significantly correlated with white matter atrophy in the infarct hemisphere (Spearman's rho = 0.59, p = 0.027). Both of these associations were significant after adjustment for the false discovery rate and were validated using the secondary volumetric method. MRS may be useful in the prediction of white matter atrophy post-stroke and in the testing of novel neurorestorative therapies.


Arteriovenous anastomoses in the skin of seals. II. The California sea lion Zalophus californianus and the northern fur seal Callorhinus ursinus (Pinnipedia: Otariidae).
The structure, distribution and density of arteriovenous anastomoses (AVAs) were studied in body and flipper skin of a California sea lion and a nothern fur seal. In both animals AVAs consisted of arterial, intermediate and venous segments, and were generally larger and more tortuous in the sea lion than in the fur seal. In the sea lion the majority of AVAs (72%) occurred in the deeper region of the dermis, and the density was significantly greater in the flippers than in the body. In the northern fur seal most AVAs (76%) occurred in the superficial region of the dermis; the density of AVAs in flipper skin was significantly higher than in body skin, and the density in the hind flipper was significantly greater than in the foreflipper. Arteriovenous anastomoses are important in the regulation of body temperature in seals; when these animals are on land, AVAs function to dissipate body heat, and vascular thermoregulation occurs in the flippers but notover the general body surface. Due to differences in distribution and density, AVAs play a more significant role in thermoregulation in the northern fur seal than in the California sea lion.


Dredging for dilution: A simulation based case study in a Tidal River.
A 2-D hydrodynamic finite element model with a Lagrangian particle module is used to investigate the effects of dredging on the hydrodynamics and the horizontal dilution of pollutant particles originating from a wastewater treatment facility (WWTF) in tidal Oyster River in New Hampshire, USA. The model is driven by the semi-diurnal (M2) tidal component and includes the effect of flooding and drying of riverine mud flats. The particle tracking method consists of tidal advection plus a horizontal random walk model of sub-grid scale turbulent processes. Our approach is to perform continuous pollutant particle releases from the outfall, simulating three different scenarios: a base-case representing the present conditions and two different dredged channel/outfall location configurations. Hydrodynamics are investigated in an Eulerian framework and Lagrangian particle dilution improvement ratios are calculated for all cases. Results show that the simulated hydrodynamics are consistent with observed conditions. Eulerian and Lagrangian residuals predict an outward path suggesting flushing of pollutants on longer (>M2) time scales. Simulated dilution maps show that, in addition to dredging, the relocation of the WWTF outfall into the dredged main channel is required for increased dilution performance. The methodology presented here can be applied to similar managerial problems in all similar systems worldwide with relatively little effort, with the combination of Lagrangian and Eulerian methods working together towards a better solution. The statistical significance brought into methodology, by using a large number of particles (16000 in this case), is to be emphasized, especially with the growing number of networked parallel computer clusters worldwide. This paper improves on the study presented in Bilgili et al., 2006b, by adding an Eulerian analysis.


High-performance liquid chromatographic assay of a new non-steroidal anti-inflammatory agent, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid, in human plasma and urine.
A high-performance liquid chromatographic method for the quantitation of a new anti-inflammatory agent, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid (CN-100; I), has been developed. The assay consists in extracting samples containing I and mefenamic acid, the internal standard, under acidic conditions and analysis by reversed-phase chromatography using ultraviolet detection at 330 nm. Preliminary plasma concentration-time and cumulative urinary excretion profiles from a healthy subject following oral administration of the tablet formulation are presented. This method is simple, sensitive and reproducible and is applicable to studies of the pharmacokinetic behaviour of I in humans.


Transient response in a somatic shunt cable model for synaptic input activated at the terminal.
Rall's neuron model is extended by including a non-uniform time constant together with synaptic input modeled as a square step of conductance. An analytic solution (in series form) for the electrotonic potential is obtained. The major conclusion reached is that a lower somatic time constant attenuates the amplitude of the potential at the soma, brought about by the activation of a synapse located at the distal end of the dendritic cable in an initially polarized neuron.


Clinical Implications of Basilar Artery Plaques in the Pontine Infarction with Normal Basilar Angiogram: A High-Resolution Magnetic Resonance Imaging Study.
Using high-resolution magnetic resonance imaging (HR-MRI), we investigated the impact of basilar artery plaques that were not detected by magnetic resonance angiography (MRA) on the functional outcomes of patients with acute pontine infarction. A total of 40 patients with acute pontine infarction and normal basilar findings on MRA prospectively underwent HR-MRI for detection of basilar artery plaques. A relevant plaque was defined as one on the dorsal side of basilar artery, the same side of the ischemic lesion, and the same axial slices of the ischemic lesion. We analyzed the relationship between the relevant basilar artery plaques and the functional outcomes at 3 months. The initial National Institutes of Health Stroke Scale score (3.5 versus 2.0, P = .012), and the incidences of neurological deterioration (42.9% versus 6.3%, P = .031) and unfavorable functional outcome (71.4% versus 12.5%, P = .001) were higher in patients with relevant basilar artery plaques than in those without. On multiple regression analysis, the relevant basilar artery plaque was a significant and independent predictor of unfavorable functional outcome (odds ratio, 6.662; 95% confidence interval, 1.117-39.735; P = .037). The presence of a relevant basilar artery plaque was closely related with unfavorable functional outcome in patients with acute pontine infarction even if the patients' MRA showed normal basilar findings.


Piglets with maternally derived antibodies from sows immunized with rAdV-SFV-E2 were completely protected against lethal CSFV challenge.
Classical swine fever (CSF) is an economically important infectious disease of pigs caused by Classical swine fever virus (CSFV). To facilitate the eradication of CSF in endemic areas, a marker vaccine enabling differentiation of infected from vaccinated animals (DIVA) is urgently needed. Previously, we have demonstrated that the DIVA vaccine rAdV-SFV-E2, an adenovirus-vectored Semliki Forest virus replicon expressing the E2 glycoprotein of CSFV, induces complete protection from lethal CSFV challenge. The aim of this study was to investigate whether maternally derived antibodies (MDAs) from sows immunized with rAdV-SFV-E2 can effectively protect piglets against lethal CSFV challenge. Three groups of five-week-old piglets (n=4), with or without MDAs, were challenged with the highly virulent CSFV Shimen strain. Clinical signs, CSFV-specific antibodies, viremia and pathological and histopathological changes were monitored. The results showed that the piglets with MDAs from the sow immunized with rAdV-SFV-E2 were protected clinically, virologically and pathologically, while the piglets with undetectable MDAs from the rAdV-SFV-E2-immunized sow were partially protected (2/4 survival), in contrast with the piglets from the non-vaccinated sow, which displayed CSF-typical clinical signs, viremia, deaths (4/4) and pathological/histopathological lesions. These results indicate that MDAs from the sow immunized with rAdV-SFV-E2 are able to confer full passive immunity to newborn piglets.


A prospective study of fatigue trajectories among in-centre haemodialysis patients.
Fatigue is common and debilitating among dialysis patients. The aim of this study was to understand the longitudinal trajectory of fatigue and consider sociodemographic, clinical, and psychological factors that are related to variation in fatigue levels over time. A prospective study of fatigue with yearly assessments over 3 years among prevalent in-centre haemodialysis (HD) patients. Fatigue severity was measured using the Chalder Fatigue Questionnaire and fatigue-related functional impairment using the Work and Social Adjustment Scale. The trajectories of fatigue outcomes were examined using piecewise growth models, using length of time on dialysis as time. Sociodemographic, clinical, and psychological predictors of fatigue were assessed using linear growth models, using follow-up time. One hundred and seventy-four prevalent HD patients completed baseline measures, 118 at 12 months, 84 at 24 months, and 66 at 36 months. Fatigue severity scores decreased by 0.15 each year. Fatigue-related functional impairment increased by 1.17 each year. In adjusted linear growth models, non-white ethnicity was a significant predictor of lower initial fatigue severity (B = -2.95, 95% CI -5.51 to -0.40) and a greater reduction in fatigue severity of 1.60 each year (95% CI 0.35-2.36). A one-point increase in damage beliefs was associated with a 0.36 increase in fatigue-related functional impairment each year (95% CI -0.61 to -0.01). Damage beliefs predicted an increase in fatigue-related functional impairment over time. However, the data strongly suggested that fatigue outcomes vary by length of time on dialysis. Statement of contribution What is already known on this subject? At least 1 in 2 haemodialysis (HD) patients are clinically fatigued. Growing evidence is available on the important role of psychological factors in fatigue across chronic conditions. The contribution of psychological factors, beyond distress, to fatigue in HD has not been examined to date. What does this study add? Ethnicity played a role in the initial level of fatigue severity and over time. Damage beliefs predicted an increase in fatigue-related impairment over time. Data strongly suggested that fatigue outcomes vary by length of time on dialysis.


Synthesis, Fungitoxic Activity against Botrytis cinerea and Phytotoxicity of Alkoxyclovanols and Alkoxyisocaryolanols.
Clovane and isocaryolane derivatives have been proven to show several levels of activity against the phytopathogenic fungus Botrytis cinerea. Both classes of sesquiterpenes are reminiscent of biosynthetic intermediates of botrydial, a virulence factor of B. cinerea. Further development of both classes of antifungal agent requires exploration of the structure-activity relationships for the antifungal effects on B. cinerea and phytotoxic effects on a model crop. In this paper, we report on the preparation of a series of alkoxy-clovane and -isocaryolane derivatives, some of them described here for the first time (2b, 2d, 2f-2h, and 4c-4e); the evaluation of their antifungal properties against B. cinerea, and their phytotoxic activites on the germination of seeds and the growth of radicles and shoots of Lactuca sativa (lettuce). Both classes of compound show a correlation of antifungal activity with the nature of side chains, with the best activity against B. cinerea for 2d, 2h, 4c and 4d. In general terms, while 2-alkoxyclovan-9-ols (2a-2e) exert a general phytotoxic effect, this is not the case for 2-arylalkoxyclovan-9-ols (2f-2i) and 8-alkoxyisocaryolan-9-ols (4a-4d), where stimulating effects would make them suitable candidates for application to plants.


Protocol for the development of guidance for collaborator and partner engagement in health care evidence syntheses.
Involving collaborators and partners in research may increase relevance and uptake, while reducing health and social inequities. Collaborators and partners include people and groups interested in health research: health care providers, patients and caregivers, payers of health research, payers of health services, publishers, policymakers, researchers, product makers, program managers, and the public. Evidence syntheses inform decisions about health care services, treatments, and practice, which ultimately affect health outcomes. Our objectives are to: A. Identify, map, and synthesize qualitative and quantitative findings related to engagement in evidence syntheses B. Explore how engagement in evidence synthesis promotes health equity C. Develop equity-oriented guidance on methods for conducting, evaluating, and reporting engagement in evidence syntheses METHODS: Our diverse, international team will develop guidance for engagement with collaborators and partners throughout multiple sequential steps using an integrated knowledge translation approach: 1. Reviews. We will co-produce 1 scoping review, 3 systematic reviews and 1 evidence map focusing on (a) methods, (b) barriers and facilitators, (c) conflict of interest considerations, (d) impacts, and (e) equity considerations of engagement in evidence synthesis. 2. Methods study, interviews, and survey. We will contextualise the findings of step 1 by assessing a sample of evidence syntheses reporting on engagement with collaborators and partners and through conducting interviews with collaborators and partners who have been involved in producing evidence syntheses. We will use these findings to develop draft guidance checklists and will assess agreement with each item through an international survey. 3. The guidance checklists will be co-produced and finalised at a consensus meeting with collaborators and partners. 4. We will develop a dissemination plan with our collaborators and partners and work collaboratively to improve adoption of our guidance by key organizations. Our international team will develop guidance for collaborator and partner engagement in health care evidence syntheses. Incorporating partnership values and expectations may result in better uptake, potentially reducing health inequities.


Rare gastrointestinal stromal tumor in an ileal conduit detected by recurrent massive bleeding from the stoma.
The development of secondary tumors is a well-known late adverse event after urinary diversion. However, the frequency of secondary tumors after an ileal conduit is the lowest compared to other methods used for urinary diversion. We observed a rare case of a gastrointestinal stromal tumor in an ileal conduit detected by recurrent massive bleeding from the stoma. An 87-year-old female was hospitalized at our hospital due to recurrent bleeding from a stoma 22 years after radical cystectomy. Contrast-enhanced computed tomography revealed a 5-cm mass in her ileal conduit. She underwent a complete resection of the tumor, a histological examination of which revealed it to be a gastrointestinal stromal tumor. The condition of the patient has been good showing no recurrence or metastases 4 years after surgery. We report a rare secondary tumor, a gastrointestinal stromal tumor, arising from an ileal conduit.


Patient characteristics and availability of onsite non-rapid and rapid HIV testing in US substance use disorder treatment programs.
Racial and ethnic minorities and injection drug users (IDUs) are at increased risk of HIV infection. However, the associations between these caseload characteristics and the availability of onsite HIV testing in substance use disorder treatment programs are unknown. This study uses data collected in 2008-2009 from 198 program administrators of treatment programs participating in the National Institute on Drug Abuse's Clinical Trials Network to address this gap in the literature. Results show positive associations between the percentages of African American, Hispanic, and IDU patients and the odds of offering non-rapid onsite HIV testing versus no onsite testing. The associations between racial/ethnic composition and the availability of rapid HIV testing were more complicated. These findings suggest that many programs are responding to the needs of at-risk populations. However, programs and their patients may benefit from greater adoption of rapid testing which is less costly and better ensures that patients receive their results.


Fatigue and recovery have different effects on knee biomechanics of drop vertical jump between female collegiate and recreational athletes.
Although fatigue is known as one of the risk factors for noncontact anterior cruciate ligament injury, the effects of fatigue and recovery can be different based on the level of competition. However, it is unknown whether female recreational athletes are susceptible to fatigue or not, compared to female collegiate athletes with greater physical activity. The purpose of the present study was to examine and clarify the effects of fatigue and recovery on knee biomechanics of the drop vertical jump (DVJ) in female recreational athletes compared to female collegiate athletes. Fifteen female collegiate athletes and ten female recreational athletes were enrolled in the current study. All subjects were basketball players and Tegner activity scales were level 9 and 7, respectively. They performed DVJ before and after the fatigue protocol. Three-dimensional knee kinematics and kinetics were collected during landing phase of DVJ. The data after the fatigue protocol (first, second, and third DVJs) were compared with those before the protocol using one-way repeated measures of analysis of variance in each group. Fatigue caused significant increase of knee abduction angle at initial contact (IC) and peak abduction moments within 40 ms from IC in female recreational athletes, whereas no increases of these parameters were observed in female collegiate athletes. Moreover, recovery from fatigue seemed to be more slowly in female recreational athletes than in female collegiate athletes as smaller knee flexion moment was observed even in post-fatigue third DVJ only for female recreational athletes. Effects of fatigue on DVJ were significantly greater and continued for a longer duration in female recreational athletes compared to female collegiate athletes.


A case of monoclonal gammopathy associated with acute myelomonocytic leukemia with eosinophilia suggested to be the result of lineage infidelity.
Acute myelomonocytic leukemia (AMMoL) accompanied by monoclonal gammopathy is a rare condition, and its pathogenesis and the cytogenetic mechanism of such leukemogenesis have not been determined in detail. A case of AMMoL with eosinophilia accompanied by immunoglobulin G kappa monoclonal gammopathy is described. Immunophenotypic studies of the peripheral blood and bone marrow mononuclear cells revealed no evidence of abnormally proliferating cells of B-lineage. DNA analyses of bone marrow mononuclear cells containing leukemic cells revealed rearrangement of the kappa-light chain (Igkappa) gene and c-myc and c-jun proto-oncogenes. The intensities of the rearranged bands for these genes on Southern blot analysis suggested the existence of a major population of leukemic cells with rearranged Igkappa gene and minor population(s) of leukemic cells with rearranged c-myc and/or c-jun proto-oncogene(s) in the patient's bone marrow and indicated the occurrence of genetic evolutionary changes in leukemic cells in this patient before starting chemotherapy. These results suggest that these leukemic cells are the most likely candidate for immunoglobulin G kappa monoclonal protein production, and structural abnormalities of c-myc and c-jun proto-oncogenes may have contributed to the evolution of leukemic cells in this patient.


Identification of the human DPR core promoter element using machine learning.
The RNA polymerase II (Pol II) core promoter is the strategic site of convergence of the signals that lead to the initiation of DNA transcription1-5, but the downstream core promoter in humans has been difficult to understand1-3. Here we analyse the human Pol II core promoter and use machine learning to generate predictive models for the downstream core promoter region (DPR) and the TATA box. We developed a method termed HARPE (high-throughput analysis of randomized promoter elements) to create hundreds of thousands of DPR (or TATA box) variants, each with known transcriptional strength. We then analysed the HARPE data by support vector regression (SVR) to provide comprehensive models for the sequence motifs, and found that the SVR-based approach is more effective than a consensus-based method for predicting transcriptional activity. These results show that the DPR is a functionally important core promoter element that is widely used in human promoters. Notably, there appears to be a duality between the DPR and the TATA box, as many promoters contain one or the other element. More broadly, these findings show that functional DNA motifs can be identified by machine learning analysis of a comprehensive set of sequence variants.


Phylogenetic significance of the characteristics of simple sequence repeats at the genus level based on the complete chloroplast genome sequences of Cyatheaceae.
The simple sequence repeats (SSRs) of plant chloroplasts show considerable genetic variation and have been widely used in species identification and phylogenetic relationship determination. Whether chloroplast genome SSRs can be used to classify Cyatheaceae species has not yet been studied. Therefore, the chloroplast genomes of eight Cyatheaceae species were sequenced, and their SSR characteristics were compared and statistically analyzed. The results showed that the chloroplast genome structure was highly conserved (genome size: 154,046-166,151 bp), and the gene content (117 genes) and gene order were highly consistent. The distribution characteristics of SSRs (number, relative abundance, relative density, GC content) showed taxon specificity. The primary results were the total numbers of SSRs and mononucleotides: Gymnosphaera (61-67 and 40-47, respectively), Alsophila (121-122 and 95-96), and Sphaeropteris (102-103 and 77-80). Statistical and clustering analyses of SSR characteristics showed that their distribution was consistent with the recent classification of Cyatheaceae, which divided the eight Cyatheaceae species into three genera. This study indicates that the distribution characteristics of Cyatheaceae chloroplast SSRs can provide useful phylogenic information at the genus level.


Model development and validation of personal exposure to PM2.5 among urban elders.
Indirect measurements through a combination of microenvironment concentrations and personal activity diaries provide a potentially useful alternative for PM2.5 exposure estimates. This study was to optimize a personal exposure model based on spatiotemporal model predictions for PM2.5 exposure in a sub-cohort study. Personal, home indoor, home outdoor, and ambient monitoring data of PM2.5 were conducted for an elderly population in the Taipei city of Taiwan. The proposed microenvironment exposure (ME) models incorporate PM2.5 measurements and individual time-activity information with a generalized estimating equation (GEE) analysis. We evaluated model performance with daily personal PM2.5 exposure based on the coefficient of determination, accuracy, and mean bias error. Ambient and home outdoor measures as exposure surrogates are likely to under- and overestimate personal exposure to PM2.5 in our study population, respectively. Measured and predicted indoor exposures were highly correlated with personal PM2.5 exposure. The awareness of peculiar smells is an important factor that significantly increases personal PM2.5 exposure by 46-70%. The model incorporating home indoor PM2.5 can achieve the highest agreement (R2 = 0.790) with personal exposure and the lowest measurement error. The ME model with the GEE analysis combining home outdoor PM2.5 determined by LUR model with a machine learning technique can improve the prediction (R2 = 0.592) of personal PM2.5 exposure, compared with the prediction of the traditional LUR model (R2 = 0.385).


Blood vascular organization of the walls of vermiform appendix from human fetus. Examination of vascular corrosion casts in SEM.
Ten human vermiform appendices obtained from fetal corpses (160.0-240.0 mm of CRL) were examined using injection-micro corrosion method. Blood vascular bed reproduced with this method was observed with scanning electron microscope (SEM). Blood vascular bed structure of foetal appendix has been described, simultaneously with produced by them plexuses and organisation of microcirculation in a wall of the appendix. Collected results have been compared with data of other authors who conducted similar research on adult human appendices and appendices of several animal species.


Cellulose-based slow-release nitrogen fertilizers: Synthesis, properties, and effects on pakchoi growth.
The application of most slow-release fertilizers is limited by complex preparation processes and short slow-release periods. In this study, carbon spheres (CSs) were prepared by a hydrothermal method using cellulose as the raw material. Using CSs as the fertilizer carrier, three new carbon-based slow-release nitrogen fertilizers were prepared using direct mixing (SRF-M), water-soluble immersion adsorption (SRFS), and co-pyrolysis (SRFP) methods, respectively. Examination of the CSs revealed regular and ordered surface morphology, enrichment of functional groups on the surfaces, and good thermal stability. Elemental analysis showed that SRF-M was rich in nitrogen (total nitrogen content of 19.66 %). Soil-leaching tests showed that the total cumulative nitrogen release of SRF-M and SRF-S was 55.78 % and 62.98 %, respectively, which greatly slowed down the release of nitrogen. Pot experiment results revealed that SRF-M significantly promoted the growth of pakchoi and improved crop quality. Thus, SRF-M was more effective in practical applications than the other two slow-release fertilizers. Mechanistic studies showed that CN, -COOR, pyridine-N and pyrrolic-N participated in nitrogen release. This study thus provides a simple, effective, and economical method for the preparation of slow-release fertilizers, providing new directions for further research and the develop of new slow-release fertilizers.


Development of youth aerobic-capacity standards using receiver operating characteristic curves.
Cardiovascular fitness has important implications for current and future health in children. In this paper, criterion-referenced standards are developed for aerobic capacity (an indicator of cardiovascular fitness) based on receiver operating characteristic (ROC) curves. The sample was drawn from participants aged 12-18 years in the National Health and Nutrition Examination Survey (1999-2002, N=1966). Subjects completed a treadmill exercise test from which maximal oxygen uptake (VO(2)max) was estimated from heart rate response. Metabolic syndrome was classified using previously published standards based on the National Cholesterol Education Program/Adult Treatment Panel III adult values at age 20 years. Using aerobic fitness z-scores as the test and metabolic syndrome as the criterion, ROC curve analysis was used to identify aerobic-capacity thresholds. The area under the curve (AUC) value for boys (83.1%) was high, indicating good utility for detecting risk of metabolic syndrome with aerobic fitness values. The AUC for girls (77.2%) was slightly below the recommended value of 80%. Although the ROC plots identified a defensible point for classifying levels of fitness, the approach in the present study was to establish two independent thresholds, one aimed at high specificity and one aimed at high sensitivity. The resulting z values for the low- and higher-risk threshold lines were then converted back to VO(2)max estimates using published LMS (L=skewness, M=median, and S=coefficient of variation) parameters. Values at the low-risk threshold ranged from 40 to 44 mL/kg/min for boys and from 38 to 40 mL/kg/min for girls. In summary, aerobic fitness can be used with moderate accuracy to differentiate between adolescents with and without metabolic syndrome. Age- and gender-specific aerobic-capacity thresholds for creating separate risk groups were identified using nationally representative growth percentiles.


Laparoscopic diverticulectomy of perforated right-sided colonic diverticulitis.
The perforation of the right-sided colonic diverticulitis (RSCD) is a rare surgical emergency with highly variable clinical presentations. The preoperative distinction between acute appendicitis and perforated diverticulitis represent a dilemma for surgeon. The laparoscopic repair is a feasible method instead of ileocecectomy in selected cases.


Peroxisomal disorders.
The different types of adrenoleukodystrophy are considered with their clinical and biochemical features, particularly the excess of very-long-chain fatty acids. Then other conditions which show this latter finding are described, including the Zellweger cerebrohepatorenal syndrome, hyperpipecolic acidemia and Refsum disease. The role of peroxisomes is discussed and the different ways in which their functions can be disordered. The possibilities of treating these diseases is at the moment limited but examples are given of research already carried out in this field.


Hepatitis B virus proteins expressed by recombinant vaccinia viruses: influence of preS2 sequence on expression surface and nucleocapsid proteins in human diploid cells.
Fifteen vaccinia virus (VV) recombinants derived from VV strains Praha, LIVP and DD (i.e. Dryvax Wyeth vaccine-derived) and expressing genes for S, preS2-S or c antigens of hepatitis B virus (HBV) were tested in monkey CV-1 cells and human diploid LEP cells. The production of infectious virus was found to be alike in all the recombinants and parental viruses as well. However, several recombinants produced markedly lesser amounts of S and preS2 antigens in LEP cells than in CV-1 cells. This reduction was independent of the parental virus used. There was, however, a relationship between the production of preS2 in CV-1 cells and the production of S and preS2 antigens in LEP cells; in general, recombinants efficiently inducing preS2 antigen formation in CV-1 cells produced markedly reduced amounts of S and preS2 antigens in LEP cells. Reduction of HBV antigen production in LEP cells was not apparent in recombinants expressing only S or c antigens of HBV, and the production of c antigen by double recombinants was not influenced by simultaneous expression of preS2 and S. The various recombinants also differed in the ratio of S:preS2 antigen formation. This difference seemed to be associated with the length of the untranslated leader sequence preceding preS2 but not with the parental virus or cell type used. The titers of antibodies against S and preS2 antigens induced in mice immunized with different recombinants differed markedly. The differences in the ratio of S:preS2 antigen production in vitro were not reflected in vivo by S:preS2 antibody ratio.


Designing sustainable work systems: the need for a systems approach.
There is a growing discussion concerning sustainability. While this discussion was at first mainly focused on a society level--and sometimes regarding especially environmental problems, one can now see that this topic is of increasing relevance for companies worldwide and even the social dimension of this three pillar approach is gaining more and more importance. This leads to some questions: Is sustainability already a part of human factors thinking or do we have to further develop our discipline? How can we define sustainable work systems? What are the topics we have to consider? Do we need a new systems ergonomics perspective regarding whole value creation chains and a life-cycle perspective concerning products (and work systems)? How can we deal with potential contradictions about social, ecological, and economic goals?


Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABA(A) receptors clustered at neocortical synapses.
Maintaining the proper balance between excitation and inhibition is necessary to prevent cortical circuits from either falling silent or generating epileptiform activity. One mechanism through which cortical networks maintain this balance is through the activity-dependent regulation of inhibition, but whether this is achieved primarily through changes in synapse number or synaptic strength is not clear. Previously, we found that 2 d of activity deprivation increased the amplitude of miniature EPSCs (mEPSCs) onto cultured visual cortical pyramidal neurons. Here we find that this same manipulation decreases the amplitude of mIPSCs. This occurs with no change in single-channel conductance but is accompanied by a reduction in the average number of channels open during the mIPSC peak and a reduction in the intensity of staining for GABA(A) receptors (GABA(A)Rs) at postsynaptic sites. In addition, the number of synaptic sites that express detectable levels of GABA(A)Rs was decreased by approximately 50% after activity blockade, although there was no reduction in the total number of presynaptic contacts. These data suggest that activity deprivation reduces cortical inhibition by reducing both the number of GABA(A)Rs clustered at synaptic sites and the number of functional inhibitory synapses. Because excitatory and inhibitory synaptic currents are regulated in opposite directions by activity blockade, these data suggest that the balance between excitation and inhibition is dynamically regulated by ongoing activity.


Effective gating charge of ion channels induced by toxin syringomycin E in lipid bilayers.
To elucidate the voltage gating of syringomycin E (SRE) ion channels in lipid bilayers, the effective gating charge q was measured under different conditions. It was shown that q and its sign are dependent on membrane surface charge, dipole potential, and the outer potential (Delta phi). The q values were positive for charged bilayers and negative for uncharged bilayers bathed in the same 0.1 M NaCl solutions. Effects of dipole modifying agents on the gating properties of SRE channels were measured. In uncharged bilayers, addition of phloretin resulted in an increase of q values. For charged bilayers, the presence of RH-421 or 6-ketocholestanol leads to the reverse in the sign of q from positive to negative. The q values were potential-dependent at higher negative voltages with charged membranes bathed in solutions with high salt concentrations. It is concluded that lipid molecules participating in the SRE channel structure contribute to channel formation work due to Coulomb and dipolar interactions with the electric field applied to a membrane. The potential dependence of q is explained by interactions of charged and uncharged lipids with SRE molecules in the channels.


[Organization of anesthesiological and resuscitative care delivered to the wounded and patients in the large specialized hospital].
On the basis of an analysis of the specific features of organization of anesthesiological and resuscitative care, the authors formulate a number of points that are of great importance for the quality of work. They give the optimal recommendations for organizing the professional activities of physicians of intensive care units and consultants. The paper presents conceptual sketches of the training of anesthesiologists working in a specialized center are presented. The authors show it necessary to follow the principle in the gradation of anesthesiological and resuscitative care.


Disparities in fertility knowledge among women from low and high resource settings presenting for fertility care in two United States metropolitan centers.
Few studies have examined health literacy and fertility knowledge among women from low income, socio-culturally diverse communities presenting for fertility care in the United States. Our study sought to examine demographic predictors of fertility-related knowledge among infertile women from low and high-resource communities in two major metropolitan centers in the United States. Fertility Knowledge Assessments were administered to women presenting for fertility care at county medical centers serving low-resource, largely immigrant patients and to women from largely affluent populations presenting to comprehensive fertility centers in two cities. The influence of demographic predictors on fertility knowledge was examined through regression analysis. A total of 143 women were included in our analysis. In the county hospital/low resource clinic (LR, n = 70), the mean age was 32.8 ± 6.1 years vs 35.0 ± 5.0 years in the fee-for-service/high resource clinic (HR, n = 73). Among the LR patients, 74% were immigrants, 71% had an annual income <$25,000 and 52% had completed high school. Among HR patients, 36% were immigrants, 60% had an annual income >$100,000, and 95% had some college or above. On average, women from HR settings scored 3.0 points higher on the Fertility Knowledge Assessment than their LR counterparts (p < 0.001). Upon multivariate analysis, education level remained the sole independent factor associated with fertility knowledge assessment score (p < 0.001). Stratifying by resource level revealed that income was highly associated with fertility knowledge (p < 0.01) among high resource individuals even when adjusting for education level. Women from low resource, largely immigrant communities, seeking fertility care have greater disparities in fertility knowledge and lower health literacy compared to women from high resource clinical settings. Further studies are needed to understand these barriers and to develop targeted inventions to lower disparities and improve care for these vulnerable populations.


Immunocytochemical localization of capsid-related particles in subcellular fractions of poliovirus-infected cells.
The structural proteins of poliovirus can assemble into a series of different configurations (capsid-related particles, CRP). Only some seem to be true capsid precursors and the role of most CRP in morphogenesis is unclear. We used electron microscopic immunocytochemistry with monoclonal antibodies recognizing different CRP [protomers, pentamers, 65S empty capsids (EC), 74S-EC, and virions] to locate CRP in subcellular fractions containing virus-induced vesicles associated with the viral replication complex. We found pentamer antigenic CRP to be associated with the replication complex. The same pentamer antigenicity was exhibited by novel, "capsid-like" structures attached to the surface of the virus-induced vesicles. Upon solubilization of the vesicular fraction, mainly 65S-EC and only negligible amounts of pentamers were found by sucrose gradient analysis and by immunoprecipitation. We show that the pentamer antigenic particles are converted into 65S-EC when their membranous support is dissolved. We propose that the vesicular membrane prevents the assembly of 65S-EC and keeps the pentamer antigenic CRP in the appropriate concentration and configuration for association with the nascent progeny RNA.


Silk protein fibroin from Antheraea mylitta for cardiac tissue engineering.
The human heart cannot regenerate after an injury. Lost cardiomyocytes are replaced by scar tissue resulting in reduced cardiac function causing high morbidity and mortality. One possible solution to this problem is cardiac tissue engineering. Here, we have investigated the suitability of non-mulberry silk protein fibroin from Indian tropical tasar Antheraea mylitta as a scaffold for engineering a cardiac patch in vitro. We have tested cell adhesion, cellular metabolic activity, response to extracellular stimuli, cell-to-cell communication and contractility of 3-days postnatal rat cardiomyocytes on silk fibroin. Our data demonstrate that A. mylitta silk fibroin exhibits similar properties as fibronectin, a component of the natural matrix for cardiomyocytes. Comparison to mulberry Bombyx mori silk protein fibroin shows that A. mylitta silk fibroin is superior probably due to its RGD domains. 3D scaffolds can efficiently be loaded with cardiomyocytes resulting in contractile patches. In conclusion, our findings demonstrate that A. mylitta silk fibroin 3D scaffolds are suitable for the engineering of cardiac patches.


COVID-19 and Oncology: Service transformation during pandemic.
The COVID-19 pandemic has challenged healthcare systems around the world, where resources have refocused on increasing critical bed capacity to prepare for the peak in incidence of COVID-19. Oncology faces an unprecedented challenge as patients require multidisciplinary care and are more likely to be immunosuppressed. Services in oncology have been transformed using minimal resources over a short period of time. This transformation continues and telemedicine is playing a key role. We explore how services in oncology have transformed to deliver services including consultations, systemic anticancer therapy, and surgery for patients, while shielding them from contracting COVID-19. We assess the risks and benefits of the service transformation in the immediate, interim, and long term, and how telemedicine supports the process. We performed a comprehensive review of the literature using suitable keywords on the search engines of PubMed, SCOPUS, Google Scholar, and latest official data from May to June 2020. Through the published literature on this topic, we discuss the transformations in oncology and the impact on patients and healthcare workers due to the COVID-19 pandemic. We reflect on the lessions from COVID-19 and assess the role of telemedicine in the future of oncology services. Transformation of services in oncology effectively shields patients from COVID-19 infections, and telemedicine plays a role in virtual consultations. The long-term effects are yet to be seen, such as safety of home-based treatment, and effectiveness of virtual communication on patient care. As oncology requires a multidisciplinary approach, telemedicine will play a key role to improve patient-centered cancer care in the future.


Transfusion of leukoreduced cellular blood components from cytomegalovirus-unscreened donors in allogeneic hematopoietic transplant recipients: analysis of 72 recipients.
Leukoreduction of blood components has been considered a safe alternative to screening donors for CMV. The objective of this study is to analyze the effectiveness of bedside leukoreduction in preventing CMV transmission. We retrospectively studied 72 transplant recipients and donors who were CMV-seronegative pairs. All patients were transfused with CMV-unscreened cellular blood products leukoreduced at the bedside using leukoreduction filters. Quality control measures performed monthly in our leukoreduced blood components consistently demonstrated that at least 95% of the units sampled meet the leukoreduction criterion established by the American Association of Blood Banks standards. The CMV status of the recipients and donors was determined before transplantation by the latex agglutination assay. Recipients were observed for at least 100 days after transplantation. CMV cultures of urine, buffy coat, bone marrow, and bronchial washings were done weekly when indicated. CMV antigenemia testing was performed twice weekly: 11 transplant recipients seroconverted after transplantation. One patient was positive for CMV antigenemia 4 months after transplantation, but did not have CMV infection. Two of 61 patients who were not seroconverted were CMV antigenemia positive and did not have CMV infection: leukoreduction of cellular blood products is an efficient method of preventing CMV infection.


The role of radiotherapy in the management of spinal cord glioma.
To determine the role of radiotherapy in the management of spinal cord gliomas. Thirty-six patients with spinal cord glioma treated between 1979 and 1993 were examined. The patients had 13 astrocytic tumors (7 astrocytomas, 4 anaplastic astrocytomas, 2 glioblastomas), 22 ependymal tumors (18 ependymomas, 4 myxopapillary ependymomas), and 1 unclassified glioma. Fifteen of the patients were treated by surgery alone, but the remaining 21 patients also received postoperative radiotherapy. Total resection was performed on 1 astrocytoma and 13 ependymomas. In general, 40-50 Gy/16-20 fractions/4-5 weeks were given after parital resection, but no radiotherapy was given after total resection. Actuarial survival was significantly better for patients with ependymal tumors than for those with astrocytic tumors (p = 0007), 5-year actuarial survival rates being 96% and 50% for patients with ependymal tumors and astrocytic tumors, respectively. For patients with ependymal tumors, there was no difference in motor function and survival between those with total resection and those with partial resection followed by radiotherapy. Actuarial 3-year survival was 80% for patients with astrocytomas and 40% for those with anaplastic astrocytomas plus glioblastomas. The difference in the degree of motor function between the patients treated with radiotherapy and those without radiotherapy was not statistically significant. One anaplastic astrocytoma and one glioblastoma patient have lived longer than 4 years after radical treatment including radiocordectomy, or irradiation using doses larger than the tolerance threshold of the spinal cord. Postoperative conventional radiotherapy is indicated after less than total resection of low-grade ependymal tumors and astrocytomas but not after total resection of ependymomas. Radiocordectomy may be an option for certain cases with high-grade astrocytic tumors.


The natural history of clinically unrecognized anal sphincter tears over 10 years after first vaginal delivery.
To estimate the influence of clinically unrecognized anal sphincter injuries detected by endoanal ultrasonography 3 months after first vaginal delivery on symptoms of anal incontinence over the subsequent 10-year period. One-hundred fifty-six consecutive primigravid women were recruited, anal endosonography performed, and bowel habit predelivery characterized by means of a validated 24-point questionnaire. After excluding four women with a clinically recognized sphincter tear after delivery and 18 who delivered by cesarean, these procedures were repeated 3 months postpartum. The questionnaire was repeated at 5 and 10 years to estimate continence change over the decade after delivery. Logistic regression was used to examine the effect of clinically unrecognized sphincter tears on continence. After delivery, continence deteriorated from baseline in 37 (28%) women, eight of whom had anal sphincter tears. Continence did not deteriorate in 97 women, six of whom had anal sphincter tears. At 10 years, 59 (55%) of 107 contactable women had continence scores greater than zero, 23 of whom had deteriorated from baseline. There was a significant relationship between a sphincter tear that was symptomatic after delivery and continence deterioration sustained at 5 and 10 years (odds ratio 2.8 for change in continence score). However, no relationship was found over 10 years for those women who sustained a sphincter tear but whose continence did not deteriorate postpartum. Ultrasonographic anal sphincter defects without postpartum incontinence are not associated with deterioration in continence over the following decade. II.


Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study.
Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2-7.5 × maximum dose), zolpidem (15 and 30 mg: 1.5-3 × maximum dose), and placebo were administered, with a 10-day washout between treatments. Subjective and objective measures, including visual analog scales (VASs), Addiction Research Center Inventory, and cognitive/psychomotor tests, were evaluated for 24-hour postdose. Suvorexant had significantly greater peak effects on "drug liking" VAS (primary endpoint) than placebo. Although effects of suvorexant on abuse potential measures were generally similar to zolpidem, they remained constant across doses, whereas zolpidem often had greater effects at higher doses. Suvorexant (all doses) had significantly fewer effects than zolpidem 30 mg on secondary measures, such as "high" VAS, Bowdle VAS, and Addiction Research Center Inventory morphine-benzedrine group. The overall incidence of abuse-related adverse events, such as euphoric mood and hallucination, was numerically lower with suvorexant than zolpidem. In agreement with its classification as a schedule IV drug, suvorexant demonstrated abuse potential, compared with placebo. The abuse potential was similar to zolpidem using certain measures, but with a reduced incidence of abuse-related adverse events. Although this suggests that the overall abuse liability of suvorexant may be lower than zolpidem, the actual abuse rates will be assessed with the postmarketing experience.


Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T helper 2 cytokines.
Fumaric acid derivates have been shown to stimulate T helper-2-cytokines (interleukin (IL)-4, -5) without affecting the T-helper-1-cytokine (IL-2, interferon (IFN)-gamma)-response. Herein, the influence of systemic treatment with the fumaric acid derivate dimethylfumarate (DMF) on the secretion of T helper-cytokines and the development of HSV-1 stromal keratitis (HSK) was studied in mice. The corneas from BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). While one group of mice was treated intraperitoneally with PBS, another group of mice received DMF at 15 mg/kg of body weight. Expression of IL-2, -4, -10 and IFN-gamma was analysed in HSV-1 activated lymphocytes by ELISA. The severity of epithelial and stromal herpetic keratitis was investigated clinically. Corneas were studied for the inflammatory cell infiltration, and the CD3-, CD4- and CD8-positive cells were analysed by immunohistochemistry. The IL-2, -4, 10 and IFN-gamma content was measured in the corneas. Virus replication in the eyes was analysed by a plaque-assay. The DTH-response, the HSV-specific T cell proliferation and the serum neutralizing antibody-titres were investigated. DMF increased IL-4 and IL-10, but not IL-2 and IFN-gamma, secretion in activated lymphocytes from the spleen. Incidence and severity of stromal HSV-1 keratitis was reduced in the DMF group (P < 0.01). In the corneas from DMF-treated mice, the numbers of CD3+ and CD4+ cells were decreased and IL-4 was increased. Severity of epithelial disease and the virus-clearance from the eyes did not differ between the PBS and DMF group of mice. DTH, HSV-specific T cell proliferation and the neutralizing antibody-titres were not impaired. DMF increased the T helper-2-cytokine secretion in activated lymphocytes. After corneal HSV-1 infection, corneas from DMF treated mice had increased IL-4 content. This is associated with an improvement of herpetic stromal keratitis and reduced corneal T cell infiltration. DMF did not impair the systemic antiviral response.


[Blood serum phospholipids in patients with tonsillitis under combinated alcohol-bacterial influence].
Blood serum phospholipids were investigated in alcohol abusing patients with tonsillitis. Most significant changes in phospholipids spectrum (low relative content of lysophospholipids and higher phosphatidylholine and phosphatidyletanolamin) in alcohol abusing patients with tonsillitis were observed, compared with alcohol abusers. This may be attributed to the prevailing influence of bacterial infection.


Effects of concentration, temperature and solvent composition on density and apparent molar volume of the binary mixtures of cationic-anionic surfactants in methanol-water mixed solvent media.
The accurate measurements on density of the binary mixtures of cetyltrimethylammonium bromide and sodium dodecyl sulphate in pure water and in methanol(1) + water (2) mixed solvent media containing (0.10, 0.20, and 0.30) volume fractions of methanol at 308.15, 318.15, and 323.15 K are reported. The concentrations are varied from (0.03 to 0.12) mol.l(-1) of sodium dodecyl sulphate in presence of ~ 5.0×10(-4) mol.l(-1) cetyltrimethylammonium bromide. The results showed almost increase in the densities with increasing surfactant mixture concentration, also the densities are found to decrease with increasing temperature over the entire concentration range, investigated in a given mixed solvent medium and these values are found to decrease with increasing methanol content in the solvent composition. The concentration dependence of the apparent molar volumes appear to be negligible over the entire concentration range, investigated in a given mixed solvent medium and the apparent molar volumes increase with increasing temperature and are found to decrease with increasing methanol content in the solvent composition.


[Expressions and significances of CRABPII and E-FABP in non-small cell lung cancer].
The cellular retinoic acid-binding protein II (CRABPII) and epidermal fatty acid-binding protein (E-FABP) both serving as the transport protein of retinoic acid (RA), through RA signal transduction pathway, commit the cell to opposite fate, apoptosis or survival. The aim of this study is to investigate the expression of CRABPII and E-FABP and significance in non-small cell lung cancer (NSCLC) and their lymph node metastases with tissue microarray technique. CRABPII and E-FABP proteins were detected in 54 normal lung tissues, 287 primary NSCLC tissues and 112 lymph node metastatic tissues by SP method of immunohistochemical staining. The expression level of CRABPII in the primary lesions was relevant to the gender of NSCLC patients, the metastasis and TNM staging of NSCLC (P<0.05), while the expression level of E-FABP was related to the grading and metastasis of NSCLC (P<0.05). The positive expression rate of E-FABP in NSCLC primary lesion was remarkably higher than that in adjacent normal lung tissues and lymph node metastases, respectively (P<0.05). The expression level of E-FABP had a recognizable advantage over that of CRABPII in NSCLC primary lesions (P<0.05). The differential expressions between CRABPII and E-FABP was correlated with the tumor size, grading, metastasis, TNM staging of NSCLC (P<0.05). The larger the tumor was and the later the TNM staging was, along with cancer metastasis, the more likely the expression of E-FABP would dominate. The expression of CRABPII and difference expression between CRABPII and E-FABP were closely related to the prognosis of NSCLC patients based on Kaplan-Meier survival analysis. E-FABP showed high exp ression in NSCLC, and the increased E-FABP expression may involved in the occurrence and development of NSCLC. CRABPII might have a negative effect in NSCLC progression, and its expression was negatively related to the prognosis of NSCLC patients.


Total Synthesis of Lignan Lactone (-)-Hinokinin.
This research paper is aimed at studying the total synthesis of pharmacologically active lignan (-)-hinokinin. The synthesis features a three-step cascade reaction involving highly stereoselective Michael addition, anion-oxidative hydroxylation, and oxygen anion cyclization to construct the pivotal butyrolactonimidate intermediate.


Reference values of postural balance in preschoolers: Age and gender differences for 4-5 years old Tunisian children.
Preschool age is a critical stage of postural balance development. Posturography normative data during this age are crucial for surveillance of postural balance and for the timely diagnosis of any dysfunction. The aim of this study was to provide normative data, specific to Tunisian preschoolers, according to age and gender, and to examine gender- and age-related differences in postural balance. Are there postural balance gender- and age-related differences in Tunisian preschoolers? The study included 410 (205 boys and 205 girls) preschool children aged between 4- and 5-year-old selected within a large geographic area of Tunisia. Postural balance was assessed using a stabilometric platform under 4 sensory conditions. The mean center of pressure velocity (CoP-V) parameter was selected for analysis. Differences between gender and age groups were analysed using the Mann-Whitney U. Normative data were expressed in percentiles. Significant gender effect was found in conditions where sensory inputs are most challenged with a significantly smaller mean CoP-V in girls compared to boys (p < 0.05). Moreover, 5-year-old children had significantly better postural balance than 4-year-old ones in almost all conditions (p < 0.05). The normative data established for Tunisian preschoolers provide useful comparative data for pediatricians, teachers and coaches for the early evaluation and monitoring of postural balance during this age. Gender and age-related differences should be considered in this population.


Applying the Delphi process to palliative care tool development: lessons learned.
The Delphi technique is an effective method for collecting and synthesizing informed opinions on a highly focused task, from a diverse group of experts who have specialized knowledge in an area of interest. This method has been successfully applied to palliative care research but not commonly to palliative care tool development. The Delphi technique has recently been employed in the development of two palliative pain assessment tools: the Edmonton Classification System for Cancer Pain (ECS-CP) and the Alberta Breakthrough Pain Assessment Tool for Research (ABPAT-R). The purpose of this paper is to: (a) report on our experience of using the Delphi technique for gathering validity evidence for the ECS-CP and ABPAT-R; (b) identify challenges in using this technique including sampling, study and survey design, consensus setting and response rates; and (c) suggest approaches that can add to its effectiveness in national and international collaborations in palliative care instrument development and research. Depending on the design, the Delphi technique can facilitate national or international cooperation both asynchronously (e.g., with mail-out or electronic surveys) and synchronously (e.g., with face-to-face meetings or videoconferencing). International input can assure palliative care tools are relevant in diverse clinical settings and practice cultures. The use of the Delphi technique in palliative care tool development may thereby facilitate international collaborations, rapid knowledge transfer, and effective uptake of novel tools across diverse palliative care settings.


Separation of capsular polysaccharide K4 and defructosylated K4 by high-performance capillary electrophoresis.
A rapid, highly sensitive and reproducible high-performance capillary electrophoresis (HPCE) method (electrokinetic chromatography with sodium dodecyl sulfate) is described for the determination of the polysaccharide from the uropathogenic Escherichia coli K4 bacteria (05:K4:H4) and its defructosylated product. The two polyanions, K4 and defructosylated K4, are separated and readily determined within 30 min on an uncoated fused-silica capillary using normal polarity at 20 kV and detection at 200 nm. A linear relationship was found for the two polysaccharides over a wide range of concentrations, from approximately 30 ng (0.5 microg/microL) to 210 ng (3.5 microg/microL). The described method was used to evaluate the defructosylation process of K4 under drastic acid conditions.


Nucleos(t)ide analogs improve long-term prognosis in patients with chronic hepatitis B-associated liver failure.
Chronic hepatitis B-associated liver failure (CHB-LF) is associated with high mortality. Antiviral therapy with nucleoside and nucleotide analogs (NUCs) has been reported to improve the short-term prognosis of patients with CHB-LF. However, the long-term effects of the therapy remain unclear. We undertook a cohort study to investigate the long-term effect of NUC-based antiviral therapy in patients with CHB-LF. A total of 976 patients with CHB-LF were enrolled between January 2001 and December 2009 at the Liver Disease Center of Ningbo No. 2 Hospital (Ningbo, China). The patients were divided into the NUC treatment group (n = 412) and control group (n = 564). The propensity score matching method was used to match the patients between the two groups to equilibrate the covariates. Survival analysis was carried out using the matched samples. The Cox proportional hazard model was used for the analysis of prognostic factors. After propensity matching, 262 pairs were successfully matched. No statistically significant difference was observed in the baseline characteristics of the matching pairs (P > 0.05). The long-term survival rate and survival duration of the NUC treatment group were higher than that of the control group (P < 0.05). Gender, age, Model for End-stage Liver Disease values, cholinesterase levels, white blood cell counts, hepatic encephalopathy, concomitant infection, and treatment with NUCs were found to be the independent factors associated with long-term prognosis. Antiviral therapy with NUCs may reduce the mortality rate and improve the long-term prognosis of patients with CHB-LF.


Analysis of industrial contaminants in indoor air. Part 2. Emergent contaminants and pesticides.
This article reviews recent literature on the analysis of several contaminants related to the industrial development in indoor air in the framework of the REACH project. In this second part, the attention is focused on emergent contaminants and biocides. Among these chemicals, phthalates, polybrominated and phosphate flame retardants, fragrances, pesticides, as well as other emerging pollutants, are increasing their environmental and health concern and are extensively found in indoor air. Some of them are suspected to behave as priority organic pollutants (POPs) and/or endocrine disrupting compounds (EDC), and can be found both in air and associated to the suspended particulate matter (PM) and settled dust. Main literature considered for this review is from the last ten years, reporting analytical developments and applications regarding the considered contaminants in the indoor environment. Sample collection and pretreatment, analyte extraction or desorption, clean-up procedures, determination techniques, and performance results are summarized and discussed.


[Effect of fasting and elemental carbohydrate feeding on the liver resistance to the action of cytostatics].
To study the influence of cyclophosphamide and methotrexate on the function of isolated perfused liver, and the hepatoprotective effect of starvation and parenteral glucose feeding, the authors conducted 57 tests on the rabbit liver. It was established that addition of cyclophosphamide, and, especially, of methotrexate into the perfusate negatively affected the function of the isolated perfused liver. Parenteral glucose feeding produced a protective effect on the isolated liver against the detrimental action of both methotrexate and cyclophosphamide.


Necrotizing external otitis in children: report of two cases and review of the literature.
Necrotizing external otitis is described almost exclusively in elderly diabetics. A review of the literature revealed 12 children, ages 2 months to 21 years, who have been described with this problem. Two additional patients are reported here. In children the male:female ratio is 1:1, whereas in adults a 2:1 male preponderance is seen. Diabetes mellitus, present in 94.7% of adults, is seen in only 21% of children. Facial nerve paralysis occurs in 35% of the children as compared to 52% of the adults. Facial paralysis was permanent in 100% of the children, but only 36.3% of the surviving adults had permanent facial paralysis. Surgical intervention had no significant effect on either group. Other pediatric complications include external auditory canal stenosis (29%), auricular cartilage deformity (11%), and sensorineural hearing loss (18%). A 40% to 50% mortality rate is seen in adults whereas no deaths have been reported in children. The clinical presentation of necrotizing external otitis in children shares some features with the disease as described in adults. However, notable differences do exist and form the basis of this report. The proposed pathophysiology of necrotizing external otitis in adults and its significance for disease in children are also discussed.


Synthesis and pharmacological evaluation of a new class of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins.
A series of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins 1a-h was prepared. Whenever possible, E and Z isomers were isolated, and their relative stabilities and their interconversions were tested. The antibacterial activity was tested against Gram-positive and Gram-negative bacteria. For compound 1c, whose Z and E forms do not interconvert rapidly, the Z form was the more active one. Among the other compounds, for which the E form is the only stable one for practical purposes, compound 1a was the most active. When compared with cefuroxime and cefotaxime, compound 1a showed slightly lower antibacterial activity but good serum level and half-life values.


A strategic informatics approach to autoverification.
Autoverification is rapidly expanding with increased functionality provided by middleware tools. It is imperative that autoverification of laboratory test results be viewed as a process evolving into a broader, more sophisticated form of decision support, which will require strategic planning to form a foundational tool set for the laboratory. One must strategically plan to expand autoverification in the future to include a vision of instrument-generated order interfaces, reflexive testing, and interoperability with other information systems. It is hoped that the observations, examples, and opinions expressed in this article will stimulate such short-term and long-term strategic planning.


Long-term follow-up of bone remodelling after cementless hip arthroplasty using different stems.
The present paper is concerned with the investigation of the phenomenon of long-term bone remodelling on cementless hip replacements. Changes in bone density in the periprosthetic region around the stem, measured by dual X-ray absorptiometry (DXA), were used as a measure of the osseous adaptation reaction. A postoperative follow-up of the use of four different types of prostheses of varying design after on average 13.3 (11.4-14.5) years. Specifically, the prostheses assessed in this study were the CLS/Spotorno stem with the Allofit cup by Zimmer, the Vision 2000 stem with the Duraloc cup by DePuy Synthes, the AlphaFit stem with the AlphaLock cup by Corin and the Mayo stem with the Trilogy cup by Zimmer. For the DXA measurement, the femur was divided into the zones suggested by Gruen et al. On the femur, there was a significant reduction in bone mineral density (BMD) in the proximal Region Of Interest (ROI) 1 (p = 0.003) and 7 (p < 0.001), whilst there was a significant increase in ROI 4 (p = 0.03). A greater degree of bone atrophy was seen in patients aged 60 years and older and in female patients. A remarkable finding when comparing the stems was a significantly greater reduction in BMD in ROI 6 (p = 0.003) in the case of the Vision 2000 stem and a markedly, but not statistically significantly smaller reduction in BMD in ROI 7 (p = 0.18) in the case of the short-stem Mayo-type prosthesis. The best clinical results were found with the use of the latter. The investigations provide a starting point for establishing a differential indication in the choice of prosthesis types, depending on age and sex, the use of short-stem prostheses, as well as the administration of bone-effective drugs for the prevention of stress shielding.


Analytical ultracentrifugation (AUC): a seminal tool offering multiple solutions.
Analytical ultracentrifugation (AUC) remains a highly versatile and widely applicable tool for the analysis of macromolecules and their interactions. The current state-of-the-art was demonstrated at a recent international meeting held in Glasgow, Scotland, in July 2017, the 23rd International Analytical Ultracentrifugation Workshop and Symposium. This special issue showcases the reports made at the meeting, which concerned the application of AUC to a wide range of topics in biochemical and polymer science including antibody and membrane protein characterisation, and protein-carbohydrate interactions. Presentations on development and testing of new instrumentation and methods of analysis were a particular feature of the meeting, including the optimisation of experimental protocols, and the latest optimised computational approaches to experimental simulation and the modelling of macromolecular structures.


Nuclease for DNA apurinic sites in chicken liver.
Chicken liver crude extract produced acid-soluble diphenylamine-positive material in the presence of depurinated and alkylated DNA, while the formation of such material from normal and single stranded DNA was comparatively low. The maximum acid-soluble material produced was not increased further by alkali, indicating that the enzymatic action is mostly directed towards apurinic sites.


Improved and Sustained Graduate Programs Diversity Outcomes: a 10-year Analysis and Summary of the Brown University IMSD Program.
This report describes the 10-year outcome of implementing practices that support and foster success of underrepresented students in science, technology, engineering, and math (STEM) graduate training at Brown University. The results show sustained improvements in compositional diversity, retention, and degree attainment of supported students relative to their peers. Among the outcomes is an increase in enrolled student diversity from 19 (35 of 179) to 26% (58 of 223) for historically underrepresented minority (URM) students and an increase in Ph.D. degree attainment from 4 (1 of 25) to 14% (6 of 44) for this group. These achievements follow the introduction and coordination of academic and co-curricular practices through the National Institutes of General Medical Sciences-funded Brown University Initiative to Maximize Student Development (IMSD) Program. At the center of these outcomes is the alignment of IMSD practices with recent diversity initiatives launched by the university. The outcomes described result from long-term commitments to building a culture that includes: (1) development of relationships that serve underrepresented students, (2) provision of a personalized education program of support and skills-based learning that supplements discipline-based research and coursework, and (3) investments in processes that build a culture that values and benefits from diversity. These practices may yield similar outcomes and success for students when applied elsewhere.