Algorithms for improved 3-D reconstruction of live mammalian embryo vasculature from optical coherence tomography data.
Robust reconstructions of the three-dimensional network of blood vessels in developing embryos imaged by optical coherence tomography (OCT) are needed for quantifying the longitudinal development of vascular networks in live mammalian embryos, in support of developmental cardiovascular research. Past computational methods [such as speckle variance (SV)] have demonstrated the feasibility of vascular reconstruction, but multiple challenges remain including: the presence of vessel structures at multiple spatial scales, thin blood vessels with weak flow, and artifacts resulting from bulk tissue motion (BTM). In order to overcome these challenges, this paper introduces a robust and scalable reconstruction algorithm based on a combination of anomaly detection algorithms and a parametric dictionary based sparse representation of blood vessels from structural OCT data. Validation results using confocal data as the baseline demonstrate that the proposed method enables the detection of vessel segments that are either partially missed or weakly reconstructed using the SV method. Finally, quantitative measurements of vessel reconstruction quality indicate an overall higher quality of vessel reconstruction with the proposed method. Results suggest that sparsity-integrated speckle anomaly detection (SSAD) is potentially a valuable tool for performing accurate quantification of the progression of vascular development in the mammalian embryonic yolk sac as imaged using OCT.


Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with a debridement, antibiotics and implant retention (DAIR): a retrospective multicenter study in France.
Introduction: In patients undergoing a « debridement, antibiotics, and implant retention » (DAIR) procedure for acute staphylococcal prosthetic joint infection (PJI), post-operative treatment with rifampin has been associated with a higher probability of success.(1,2) However, it is not known whether it is the total dose, delay of introduction or length of therapy with rifampin that is most strongly associated with the observed improved outcomes. Methods: A multicentric, retrospective cohort study of patients with acute staphylococcal hip and knee PJI treated with DAIR between January 2011 and December 2016. Failure of the DAIR procedure was defined as persistent infection, need for another surgery or death. We fitted logistic and Cox regression multivariate models to identify predictors of DAIR failure. We compared Kaplan-Meier estimates of failure probability in different levels of the 3 variables of interest - total dose, delay of introduction or length of therapy with rifampin - with the log-rank test. Results: 79 patients included (median age 71 years [63.5-81]; 55 men [70%]), including 54 (68%) DAIR successes and 25 (32%) DAIR failures. Patients observed for a median of 435 days [IQR 107.5-834]. Median ASA score significantly lower in DAIR successes than in DAIR failures (2 vs. 3, respectively p = 0.011). Bacterial cultures revealed 65 (82.3%) S. aureus and 16 (20.3%) coagulase negative staphylococci, with 2 patients being infected simultaneously with S. aureus and CNS. Among S. aureus isolates, 7 (10.8%) resistant to methicillin; 2 (3.1 %) resistant to rifampin. Median duration of antimicrobial therapy was 85 days [IQR 28.5-97.8]. Fifty-eight patients (73.4%) received rifampin at a median dose of 14.6 mg/kg/day |IQR 13-16.7], started at a median delay of 8.5 days [IQR, 4-7.5] after debridement surgery. Twenty-one patients (26.6%) developed a drug-related adverse event, leading to rifampin interruption in 6 of them (7.6% of total cohort). Determinants of DAIR failure were rifampin use (HR 0.17, IC [0.06, 0.45], p-value <0.001), association of rifampin with a fluoroquinolone (HR 0.19, IC [0.07, 0.53], p-value = 0.002) and duration of rifampin therapy (HR 0.97, IC [0.95, 1], p-value = 0.022). We did not observe a significant difference between DAIR successes and failures in rifampin use, dose and delay of introduction. In a multivariate Cox model, only duration of rifampin therapy was significantly associated with DAIR failure. Kaplan Meier estimate of DAIR failure probability was significantly higher in patients receiving less than 14 days of rifampin in comparison with those receiving more than 14 days of rifampin (p = 0.0017). Conclusion: Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with DAIR.


Splitting of Surface-Immobilized Multicompartment Micelles into Clusters upon Charge Inversion.
We investigate a morphological transition of surface-immobilized triblock terpolymer micelles: the splitting into well-defined clusters of satellite micelles upon pH changes. The multicompartment micelles are formed in aqueous solution of ABC triblock terpolymers consisting of a hydrophobic polybutadiene block, a weak polyanionic poly(methacrylic acid) block, and a weak polycationic poly(2-(dimethylamino)ethyl methacrylate) block. They are subsequently immobilized on silicon wafer surfaces by dip-coating. The splitting process is triggered by a pH change to strongly basic pH, which goes along with a charge reversal of the micelles. We find that the aggregation number of the submicelles is well-defined and that larger micelles have a tendency to split into a larger number of submicelles. Furthermore, there is a clear preference for clusters consisting of doublets and triplets of submicelles. The morphology of surface-immobilized clusters can be "quenched" by returning to the original pH. Thus, such well-defined micellar clusters can be stabilized and are available as colloidal building blocks for the formation of hierarchical surface structures. We discuss the underlying physicochemical principles of the splitting process considering changes in charge and total free energy of the micelles upon pH change.


[Computed tomographic densitometry in the diagnosis of chronic obstructive lung diseases].
The capacities of spiral computed tomography (CT) synchronized with a patient's respiration in the diagnosis of chronic obstructive lung diseases (COLD) were studied. Normal lung parenchymal density was clarified in different parts. The densitometric changes typical of bronchial asthma (BA) and COLD were studied in relation to the severity of an obstructive process. The differential diagnostic criteria of BA and COLD, including those at the early stage of the disease, are proposed. The optimized procedure of spiral CT synchronized with the patient's respiration is presented.


Ten-year trends in intensive care admissions for respiratory infections in the elderly.
The consequences of the ageing population concerning ICU hospitalisation need to be adequately described. We believe that this discussion should be disease specific. A focus on respiratory infections is of particular interest, because it is strongly associated with old age. Our objective was to assess trends in demographics over a decade among elderly patients admitted to the ICU for acute respiratory infections. A cross-sectional study was performed between 2006 and 2015 based on hospital discharge databases in one French region (2.5 million inhabitants). Patients with acute respiratory infection were selected according to the specific ICD-10 diagnosis codes recorded, including acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and community-acquired pneumonia (CAP). We also identified comorbid conditions based on any significant ICD-10 secondary diagnoses adapted from the Charlson and Elixhauser indexes. A total of 98,381 hospital stays for acute respiratory infection were identified among the 3,856,785 stays over the 10-year period. The number of patients 75 y/o and younger increased 1.6-fold from 2006 to 2015, whereas the numbers of patients aged 85-89 and ≥ 90 y/o increased by 2.5- and 2.1-fold, respectively. Both CAP and AECOPD hospitalisations significantly increased for all age groups over the decade. ICU hospitalisations for respiratory infection increased 2.7-fold from 2006 to 2015 (p = 0.0002). The greatest increases in the use of ICU resources were for the 85-89 and ≥ 90 y/o groups, which corresponded to increases of 3.3- and 5.8-fold. Indeed, the proportion of patients hospitalized for respiratory infection in ICU that were elderly clearly grew during the decade: 11.3% were ≥ 85 y/o in 2006 versus 16.4% in 2015 (p < 0.0001). This increase in ICU hospitalisation rate of ageing patients was not associated with significant changes in the level of care or ICU mortality except for patients ≥ 90 y/o (for whom ICU mortality dropped from 40.9 to 22.3%, p = 0.03). We observed a substantial increase in acute respiratory infection diagnoses associated with hospitalisation between 2006 and 2015, with a growing demand for critical care services. Both the absolute number and the percentage of elderly patient ICU admissions increased over the last decade, with the greatest increases being observed for patients 85 years and older.


Developing the Accuracy of Vital Sign Measurements Using the Lifelight Software Application in Comparison to Standard of Care Methods: Observational Study Protocol.
Vital sign measurements are an integral component of clinical care, but current challenges with the accuracy and timeliness of patient observations can impact appropriate clinical decision making. Advanced technologies using techniques such as photoplethysmography have the potential to automate noncontact physiological monitoring and recording, improving the quality and accessibility of this essential clinical information. In this study, we aim to develop the algorithm used in the Lifelight software application and improve the accuracy of its estimated heart rate, respiratory rate, oxygen saturation, and blood pressure measurements. This preliminary study will compare measurements predicted by the Lifelight software with standard of care measurements for an estimated population sample of 2000 inpatients, outpatients, and healthy people attending a large acute hospital. Both training datasets and validation datasets will be analyzed to assess the degree of correspondence between the vital sign measurements predicted by the Lifelight software and the direct physiological measurements taken using standard of care methods. Subgroup analyses will explore how the performance of the algorithm varies with particular patient characteristics, including age, sex, health condition, and medication. Recruitment of participants to this study began in July 2018, and data collection will continue for a planned study period of 12 months. Digital health technology is a rapidly evolving area for health and social care. Following this initial exploratory study to develop and refine the Lifelight software application, subsequent work will evaluate its performance across a range of health characteristics, and extended validation trials will support its pathway to registration as a medical device. Innovations in health technology such as this may provide valuable opportunities for increasing the efficiency and accessibility of vital sign measurements and improve health care services on a large scale across multiple health and care settings. DERR1-10.2196/14326.


Quality of life and work engagement among nursing staff at the start of the COVID-19 pandemic.
This article investigates the correlation between work engagement and work-related quality of life among nursing staff at a public hospital in São Paulo State, at the onset of the COVID-19 pandemic. A descriptive, correlational, cross-sectional study of nursing personnel was conducted from December 2020 to January 2021, using the Brazilian versions of the Work & Well-being Survey (Utrecht Work Engagement Scale - UWES) and the Work-related Quality of Life (WRQoL) scale, following Walton's model. Nursing staffs returned a strong positive correlation (r≥0.70) between the social integration domain of the WRQoL and the vigour dimension of the UWES (r=0.88; p=<0.001); a moderate positive correlation (r≥0.40≤0.69) between working conditions (WRQOL) and the vigour (r=0.40; p<0.001), dedication (r=0.40; p<0.001) and overall score (r=0.41; p<0.001) dimensions of the UWES. Correlations were positive and weak (r≤0.39) for the other WRQoL domains and the UWES dimensions. It was concluded that personnel with satisfactory levels of quality of life tend to show higher levels of engagement at work. At the onset of the COVID-19 pandemic, nursing professionals were strongly engaged and satisfied with their work-related quality of life.


Relationship between chemical structure and physicochemical properties of series of bulky organic cations and their hepatic uptake and biliary excretion rates.
To obtain more insight in the relationship between physicochemical properties of cationic drugs and their hepatobiliary transport rate, a series of 12 aminosteroidal neuromuscular blocking agents (NMBAs), supplemented with data of four related NMBAs from the literature, were investigated in the isolated perfused rat liver. A significant correlation was found between plasma protein binding and the partition coefficient octanol/Krebs (log P), confirming results from the literature with other organic cations. Evidence was found for a saturable hepatic uptake of several NMBAs, indicating that carrier-mediated uptake processes are involved. Hepatic uptake rate was closely related to the lipophilicity of the compounds; the initial extraction ratio, the apparent clearance and the intrinsic clearance were significantly correlated to log P. We did not find a significant correlation between biliary clearance and lipophilicity in the current series of compounds. Pharmacokinetics analysis of perfusate disappearance and biliary excretion data revealed that a considerable fraction of the dose of these bulky organic cations is stored in the liver and seems to not be directly available for biliary excretion. This finding is in line with earlier observations showing a pronounced accumulation of this type of compounds in mitochondria and lysosomes.


Rosin: a naturally derived excipient in drug delivery systems.
Natural polymers are primarily attractive because they are biodegradable, inexpensive, and readily available. The most important benefit of natural polymers is that they are capable for chemical modifications. One such biopolymer, rosin, and its derivatives have been pharmaceutically evaluated as microencapsulating materials, film forming agent and as binding agent in formulation of tablets. They are also employed in formulation of chewing gum bases and cosmetics. This review article provides an overview of pharmaceutical use of rosin and its derivatives as excipient in dosage forms as well as novel drug delivery systems.


Transduction analysis of transposon Tn551 insertions in the trp-thy region of the Staphylococcus aureus chromosome.
Previous studies have shown that Tn551, a 5.2-kilobase-pair transposon that determines constitutive resistance to erythromycin, can occupy a variety of chromosomal sites between thy-101 and trp-103 in Staphylococcus aureus 8325. Although many of these insertions were "silent," many others, including lys, thr, met, tyr, and trp, resulted in auxotrophic mutations. The close proximity and erythromycin-resistant phenotypes of the insertions in this region have made their mapping by transformation difficult. Analysis of these sites and similar chemically induced mutations by generalized transduction with phage 80 alpha have defined the order and relationship of these insertion sites and provided a detailed map of this region of the chromosome, including the orientation of the trp operon. The results of this study and a limited phenotypic characterization of the mutants have shown that the divergent pathway from aspartate to lysine, threonine, and methionine, several reactions in tyrosine biosynthesis, and the entire tryptophan operon are determined by this region of the chromosome. The linkage results obtained by transduction have been compared with similar data obtained previously by transformation; this comparison suggests the existence, between thy and lys, of a preferred headful cutting site for transducing phage DNA morphogenesis from the host chromosome.


Introduction of a dermatophyte polymerase chain reaction assay to the diagnostic mycology service in Scotland.
Dermatophytes are the major cause of superficial mycoses in samples submitted to Clinical Mycology, Glasgow. The most prevalent species is Trichophyton rubrum as identified classically by microscopy and culture. Recent advances in polymerase chain reaction (PCR) technology were examined for the feasibility of introducing a T. rubrum real-time PCR assay into a routine diagnostic service. To improve the diagnostic mycology service by the introduction of a real-time PCR test for T. rubrum. The DNA from 4972 nail and skin samples was obtained using the Qiagen QIAsymphony automated extractor. This DNA was subjected to real-time PCR using T. rubrum-specific primers and a probe. During phase 1 of the study, 862 samples were analysed; 446 of 470 specimens that grew T. rubrum were detected by PCR. Out of 4110 samples analysed during phase 2, 753 T. rubrum infections were diagnosed and reported within 72 h. A total of 3357 samples were negative for a fungal infection by PCR and microscopy; these were also reported within 72 h. A vast reduction in the turnaround times can be achieved using this technique as opposed to classical methods. Samples which are PCR negative but microscopy positive are still subjected to culture. Screening samples for their suitability for PCR prior to processing eliminates the application of PCR for T. rubrum on inappropriate samples such those from the scalp or pityriasis versicolor.


Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells.
Stimulation of rabbit mesenteric lymphocytes with anti-immunoglobulin antibody (anti-Ig) for 24 hr (first stage of culture) followed by the addition of enhancing soluble factor (second stage of culture) induced the formation of IgG. The presence of mitotic inhibitors, such as cytosine arabinoside (Ara-C), hydroxyurea (HU), with anti-Ig for the first 24 hr of incubation did not inhibit the production of IgG induced by anti-Ig and soluble factor. The addition of cytochalasin-B in the first stage of culture with anti-Ig did not inhibit, but rather enhanced, the formation of IgG. On the other hand, the presence of Ara-C, HU, or cytochalasin-B with soluble factor in the second stage of culture completely inhibited the production of IgG. Soluble factor preferentially induced the uptake of thymidine of anti-Ig-stimulated cells. Lipopolysaccharide (LPS) also induced the proliferation of rabbit lymphocytes, but did not induce the IgG production of anti-Ig-stimulated cells. However, LPS-stimulated cells formed a significant amounf of IgG when they were cultured with soluble factor. Anti-Ig-stimulated cells absorbed the enhancing activity of soluble factor, but non-stimulated cells did not absorb the activity. These results showed that cross-linkage of Ig receptors or LPS receptors with anti-Ig or LPS induced the formation of acceptor sites for soluble factor without the requirement of cell division and these activated cells started to proliferate and maturate to antibody-forming cells under the influence of soluble factor.


Depressive symptoms related to infertility and infertility treatments.
This article reviews depressive symptoms in women as they relate to infertility and infertility treatments. Common causes of infertility in women are discussed and the literature on depressive symptoms before and during various infertility treatments is presented. Recommendations are made from a psychiatric perspective regarding how to manage depressive symptoms in women in the context of infertility.


Effect of tumour associated tissue eosinophilia on survival of women with stage IB carcinoma of the uterine cervix.
To examine the survival of a group of women with stage IB invasive carcinoma of the uterine cervix, divided according to the expression of tumour associated tissue eosinophilia (TATE). Histological material from 81 women with stage IB squamous and adenosquamous cervical carcinomas before radiotherapy was assessed for the extent of tissue stromal eosinophilia, quantified using antibodies to human major basic protein. Twenty eight (38%) of the cases demonstrated TATE of over 30 eosinophils/mm2, with 12 (16%) having greater than 100 eosinophils/mm2. Eleven women in the series developed distant spread or recurrent pelvic disease, this group having a stromal eosinophil density significantly less (13.8/mm2) than the remainder (69.9/mm2) (p = 0.03). The actuarial five year survival rate for women with a tumour eosinophil density over 30/mm2 was 92% compared with 70% with a density under 30 mm2, with a significant difference in the survival curves for these two groups (p = 0.03). As a univariate parameter, a tumour associated tissue eosinophilia of at least modest proportions is associated with statistically improved survival in women with stage IB cervical carcinomas.


The involvement of microtubules and actin during the infection of Japanese encephalitis virus in neuroblastoma cell line, IMR32.
The role of the cytoskeleton, actin, and microtubules were examined during the process of Japanese encephalitis (JEV) infection in a human neuroblastoma cell line, IMR32. Cytochalasin D and nocodazole were used to depolymerise the cellular actin and microtubules, respectively, in order to study the effect of JEV infection in the cell. This study shows that depolymerisation of the actin cytoskeleton at early process of infection inhibits JEV infection in the cell; however infection was not inhibited when depolymerisation occurred at the later stage of infection. The microtubules, on the other hand, are required at 2 points in infection. The antigen production in the cells was inhibited when the infected cells were treated at time up to 2 hours after inoculation and there was no significant effect at later times, while the viable virus released continued to be affected until 10 hours after inoculation. In conclusion, infection of JEV in IMR32 cells required actin to facilitate early process in infection and the microtubular network is utilised as the transport system to the virus replication site and the release of mature virus.


Morbidity after midline mandibulotomy and radiation therapy.
To assess the morbidity of mandibulotomy in patients treated for neoplasms of the oropharynx and oral cavity, and to determine if postoperative radiation therapy to the mandibulotomy site carries an increased risk of complications. The medical charts of 30 patients treated between 1992 and 1996 undergoing midline mandibulotomy for tumors of the oral cavity (7 patients) and oropharynx (23 patients) were retrospectively reviewed. Three patients presented with recurrent disease, 1 of whom was previously irradiated. Twenty-five patients received postoperative radiation after mandibulotomy to a median dose of 60 Gy to the primary tumor bed, whereas 5 patients were treated with surgery alone. The patients were separated into those whose mandibulotomy site was within the radiation treatment field (n = 9), and those whose site was shielded (n = 10). Median follow-up was 27.8 months (range 5-81 months). End points included significant pain involving the mandibulotomy site, trismus, malocclusion, wound infection, osteoradionecrosis, and time to oral intake. There were no postoperative deaths. Minor wound infection or breakdown occurred in 4/30 patients (13%). All of these resolved with local care and parenteral antibiotics. More serious complications involving the mandibulotomy occurred in 2 patients (7%). One patient had chronic wound drainage at the mandibular osteotomy site, which healed after plate removal. Another patient developed osteoradionecrosis. No patient developed trismus or malocclusion. With a median follow-up of 27.8 months, 4 patients have recurred locally. The complication rate was 11% for patients whose mandibulotomy site was irradiated, and 30% for those whose site was shielded. Mandibulotomy can be safely performed in patients who are likely to require postoperative external radiation.


[Some problems related to the regulation of the glucoamylase synthesis by Endomycopsis fibuligera 21].
The effect of different sources of carbon and other components on the glucoamylase synthesis by Endomycopsis fibuligera 21 was investigated. It was demonstrated that the enzyme was actively synthesized after the complete utilization of the carbon sources and the synthesis was not related to the presence of specific substrates in the medium. It was shown that water immersed washed cells of the producer accumulated high glucoamylase activity. It is suggested that the above yeast synthesize glucoamylase in the constitutive way and that the process may be regulated by catabolite repression.


The potential of polymeric micelles in the context of glioblastoma therapy.
Glioblastoma multiforme (GBM), a type of malignant glioma, is the most common form of brain cancer found in adults. The current standard of care for GBM involves adjuvant temozolomide-based chemotherapy in conjunction with radiotherapy, yet patients still suffer from poor outcomes with a median survival of 14.6 months. Many novel therapeutic agents that are toxic to GBM cells in vitro cannot sufficiently accumulate at the site of an intracranial tumor after systemic administration. Thus, new delivery strategies must be developed to allow for adequate intratumoral accumulation of such therapeutic agents. Polymeric micelles offer the potential to improve delivery to brain tumors as they have demonstrated the capacity to be effective carriers of chemotherapy drugs, genes, and proteins in various preclinical GBM studies. In addition to this, targeting moieties and trigger-dependent release mechanisms incorporated into the design of these particles can promote more specific delivery of a therapeutic agent to a tumor site. However, despite these advantages, there are currently no micelle formulations targeting brain cancer in clinical trials. Here, we highlight key aspects of the design of polymeric micelles as therapeutic delivery systems with a review of their clinical applications in several non-brain tumor cancer types. We also discuss their potential to serve as nanocarriers targeting GBM, the major barriers preventing their clinical implementation in this disease context, as well as current approaches to overcome these limitations.


Structural and magnetic effects of meso-substitution in alkyl-substituted metalloporphyrinate pi-cation radicals: characterization of [Fe(TalkylP*)(Cl)]SbCl6 (alkyl = ethyl and n-propyl).
We report the preparation and characterization of two meso-alkyl substituted porphyrin pi-cation radical derivatives, [Fe(TalkylP(*))(Cl)]SbCl(6) (alkyl = ethyl or propyl). Both complexes have been characterized by UV/vis/near-IR, IR, and Mossbauer spectroscopy, temperature-dependent solid-state magnetic susceptibility measurements, and X-ray structure determinations. All data for both oxidized species are consistent with the formulation of the complexes as ring-oxidized iron(III) porphyrin species. The molecular structures of the two five-coordinate species have the typical square-pyramidal coordination group of high-spin iron(III) derivatives. The crystal structures also reveal that the species form cofacial pi-pi dimers with lateral shifts of 1.44 A and 3.22 A, respectively, for the propyl and ethyl radical derivatives. Both radicals exhibit porphyrin cores with alternating bond distance patterns in the inner 16-membered ring. In addition, [Fe(TEtP(*))(Cl)]SbCl(6) and [Fe(TPrP(*))(Cl)]SbCl(6) have been characterized by temperature-dependent (6-300 K) magnetic susceptibility studies, the best fitting of the temperature-dependent moments reveal strong coupling between iron spins and porphyrin radical, and a smaller magnitude of antiferromagnetic coupling between ring radicals, which are opposite to those found in the five-coordinate iron(III) OEP radicals. The differences in structure and properties of the cation radical meso-alkyl and beta-alkyl derivatives possibly reflect differences in properties of a(1u)- and a(2u)-forming radicals.


Marihuana: a forensic problem.
Early and unfounded stories concerning marihuana led to many sanctions being placed on the drug. They have also brought about the requirement that the drug be proved safe beyond any reasonable doubt for any consideration to be given to removing restrictive sanctions. Some of the misinformation has been dispelled by controlled studies of its effects. Present available research does not support the thesis of permanent damage, either physical or mental. Yet there appears to be no ongoing research that will adequately demonstrate the safety or the dangers of the drug.


Effect of deviance direction and calculation method on duration and frequency mismatch negativity (MMN).
The mismatch negativity (MMN) component of the auditory event-related potential (ERP) reflects the process of change detection in the auditory system. The present study investigated the effect of deviance direction (increment vs. decrement) and calculation method (traditional vs. same-stimulus) on the amplitude of MMN. MMN was recorded for increments and decrements in frequency and duration in 20 adults. The stimuli (standard/deviant) were 250 Hz/350 Hz (frequency MMN) and 200 ms/300 ms (duration MMN) for increment MMN and vice versa for decrement MMN. Amplitude of MMN was calculated in two ways: the traditional method (subtracting ERP to the standard from the deviant presented in the same block) and the same-stimulus method (subtracting ERP to identical stimuli presented as standard in one block and deviant in another block). We found that increments in frequency produced higher MMN amplitudes compared to decrements for both methods of calculation. For duration deviance, the decrement MMN was absent in the traditional method, while the decrement and increment MMN did not differ for the same-stimulus method. These findings suggest that the brain processes frequency increments and decrements in different ways. The results also suggest the use of same-stimulus method for the calculation of duration MMN when long duration stimuli are used.


Application of aptamers in diagnostics, drug-delivery and imaging.
Aptamers are small, single-stranded oligonucleotides (DNA or RNA) that bind to their target with high specificity and affinity. Although aptamers are analogous to antibodies for a wide range of target recognition and variety of applications, they have significant advantages over antibodies. Since aptamers have recently emerged as a class of biomolecules with an application in a wide array of fields, we need to summarize the latest developments herein. In this review we will discuss about the latest developments in using aptamers in diagnostics, drug delivery and imaging. We begin with diagnostics, discussing the application of aptamers for the detection of infective agents itself, antigens/ toxins (bacteria), biomarkers (cancer), or a combination. The ease of conjugation and labelling of aptamers makes them a potential tool for diagnostics. Also, due to the reduced off-target effects of aptamers, their use as a potential drug delivery tool is emerging rapidly. Hence, we discuss their use in targeted delivery in conjugation with siRNAs, nanoparticles, liposomes, drugs and antibodies. Finally, we discuss about the conjugation strategies applicable for RNA and DNA aptamers for imaging. Their stability and self-assembly after heating makes them superior over protein-based binding molecules in terms of labelling and conjugation strategies.


Impact of patient-doctor race concordance on rates of weight-related counseling in visits by black and white obese individuals.
The objective of this study was to assess the impact of patient-provider race concordance on weight-related counseling among visits by obese patients. We hypothesized that race concordance would be positively associated with weight-related counseling. We used clinical encounter data obtained from the 2005-2007 National Ambulatory Medical Care Surveys (NAMCS). The sample size included 2,231 visits of black and white obese individuals (ages 20 and older) to their black and white physicians from the specialties of general/family practice and general internal medicine. Three outcome measures of weight-related counseling were explored: weight reduction, diet/nutrition, and exercise. Logistic regression was used to model the outcome variables of interest. Wald tests were used to statistically compare whether physicians of each race provided counseling at different rates for obese patients of different races. We did not observe a positive association between patient-physician race concordance and weight-related counseling. We found that visits by black obese patients to white doctors had a lower odds of exercise counseling as compared to visits by white obese patients to white doctors (odds ratio (OR) = 0.54; 95% confidence interval (CI): 0.31, 0.95), and visits by black obese patients to black physicians had lower odds of receiving weight-reduction counseling than visits among white obese patients seeing black physicians (OR = 0.34; 95% CI: 0.13, 0.90). Black obese patients receive less exercise counseling than white obese patients in visits to white physicians and may be less likely than white obese patients to receive weight-reduction counseling in visits to black physicians.


Clinical outcome of isolated subcortical trabecular fractures (bone bruise) detected on magnetic resonance imaging in knees.
Isolated subcortical trabecular bone injury (bone bruise) has rarely been described. Our purpose is to report a series of patients who had a history of traumatic injury, knee effusion, normal radiographs, and initial equivocal physical examination for ligament and meniscal integrity, and who were found to have isolated injury of the trabecular bone on magnetic resonance imaging. We evaluated demographic data, physical examination findings, radiographs, magnetic resonance imaging, and clinical outcome for 23 patients. Follow-up data included time to return to preinjury activity level, International Knee Documentation Committee activity level rating before and after injury, and postinjury Lysholm scores. All magnetic resonance imaging scans were negative for associated grade III meniscal lesions and ligament injury. Time to return to preinjury activity level was under 7 months in 96% of the patients. Postinjury International Knee Documentation Committee rating was unchanged in 91% of patients. Postinjury Lysholm score was 90 or more in 91% of patients. We propose that the recognition of these injuries is important because magnetic resonance imaging can distinguish them from meniscal or ligament injury requiring surgical intervention (arthroscopy). If detected on magnetic resonance imaging as an isolated injury, surgical arthroscopy is unnecessary since these patients can be expected to recover well in the short term with restricted weightbearing and initial activity modification.


Surgical considerations in older adults with cancer.
The aging of the population is a real concern for surgical oncologists, who are increasingly being asked to treat patients who would not have been considered for surgery in the past. In many cases, decisions are made with relatively little evidence, most of which was derived from trials in which older age was a limiting factor for recruitment. This review focuses on risk assessment and perioperative management. It describes the relationship between age and outcomes for colon, lung, hepatobiliary, and head and neck cancer, which are predominantly diseases of the elderly and are a major cause of morbidity and mortality. Effective surgery requires safe performance as well as reasonable postoperative life expectancy and maintenance of quality of life. Treatment decisions for potentially vulnerable elderly patients should take into account data obtained from the evaluation of geriatric syndromes, such as frailty, functional and cognitive limitations, malnutrition, comorbidities, and polypharmacy, as well as social support. Postoperative care should include prevention and treatment of complications seen more frequently in the elderly, including postoperative delirium, functional decline, and the need for institutionalization. Surgery remains the best modality for treatment of solid tumors, and chronologic age alone should not be a determinant for treatment decisions. With adequate perioperative risk stratification, functional assessment, and oncologic prognostication, elderly patients with cancer can do as well in terms of morbidity and mortality as their younger counterparts. If surgery is determined to be the appropriate treatment modality, patients should not be denied this option because of their age.


miR-34a targets the inhibin beta B gene, promoting granulosa cell apoptosis in the porcine ovary.
During ovarian follicular growth and development, only a few follicles actually ovulate. Recently, it was found that follicular atresia is triggered by granulosa cell apoptosis, but the molecular mechanism of follicular atresia was not understood. Using flow cytometry, we found that miR-34a promotes granulosa cell apoptosis in pig ovarian follicles. In addition, inhibin beta B was found to be a miR-34a target gene, based on luciferase reporter assays, quantitative RT-PCR and Western blotting. Taken together, our data indicate that miR-34a plays an important role in granulosa cell apoptosis by targeting the INHBB gene in the porcine ovary.


The hydrophobic surface protein layer of enteroaggregative Escherichia coli strains.
The surface of three strains of enteroaggregative Escherichia coli (EAggEC) and three strains of enteropathogenic E. coli (EPEC) were examined using the freeze-substitution technique of electron microscopy and as a result an electron dense surface layer was found only on EAggEC strains but not on EPEC strains. The analysis of the outer membrane proteins by polyacrylamide gel electrophoresis revealed the existence of a unique 38 kDa protein in EAggEC strains. The protein could be easily extracted from the bacterial surface with 5 M LiCl treatment at room temperature. The antiserum raised in mice with 38 kDa protein extracted from the electrophoresed gel was immunoreacted with the surface of the bacteria of EAggEC by immunoelectron microscopy. The hydrophobic surface character of the EAggEC strains was lost after the extraction of the protein layer by LiCl. We thus conclude that the surface protein layer therefore plays an important role in the expression of the aggregative phenotype in EAggEC strains.


α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy.
The diagnosis of Parkinson's disease (PD) and atypical parkinsonian syndromes is difficult due to the lack of reliable, easily accessible biomarkers. Multiple system atrophy (MSA) is a synucleinopathy whose symptoms often overlap with PD. Exosomes isolated from blood by immunoprecipitation using CNS markers provide a window into the brain's biochemistry and may assist in distinguishing between PD and MSA. Thus, we asked whether α-synuclein (α-syn) in such exosomes could distinguish among healthy individuals, patients with PD, and patients with MSA. We isolated exosomes from the serum or plasma of these three groups by immunoprecipitation using neuronal and oligodendroglial markers in two independent cohorts and measured α-syn in these exosomes using an electrochemiluminescence ELISA. In both cohorts, α-syn concentrations were significantly lower in the control group and significantly higher in the MSA group compared to the PD group. The ratio between α-syn concentrations in putative oligodendroglial exosomes compared to putative neuronal exosomes was a particularly sensitive biomarker for distinguishing between PD and MSA. Combining this ratio with the α-syn concentration itself and the total exosome concentration, a multinomial logistic model trained on the discovery cohort separated PD from MSA with an AUC = 0.902, corresponding to 89.8% sensitivity and 86.0% specificity when applied to the independent validation cohort. The data demonstrate that a minimally invasive blood test measuring α-syn in blood exosomes immunoprecipitated using CNS markers can distinguish between patients with PD and patients with MSA with high sensitivity and specificity. Future optimization and validation of the data by other groups would allow this strategy to become a viable diagnostic test for synucleinopathies.


[Determination of one national standard for children with congenital anomalies in the National Obstetrical Registry and in the National Neonatal Registry].
To determine if the birth prevalence data on congenital malformations in the national perinatal registries, the Landelijke Verloskunde Registratie (LVR) (National Obstetrical Registry) and the Landelijke Neonatologie Registratie (LNR) (National Neonatological Registry), can be combined into one nationwide database, and if so to determine the validity of this database. Descriptive. TNO Prevention and Health, Leiden, the Netherlands. Investigation of the registered number of congenital malformations in the LVR/LNR, the amount of overlapping and the possibility of combining the LVR and LNR into one nationwide database. The validity of this database was evaluated by comparing the total number of registered children with the total number expected in the Netherlands. Furthermore the total number of children registered in the nationwide database was compared with children registered by the European registration of congenital anomalies and twins (EUROCAT) in the Northern Netherlands. The LVR and LNR were mostly complementary with respect to the registration of congenital anomalies and could be combined to one nationwide database. For sixteen important diagnoses this nationwide database contained approximately 87% of the total number expected in the Netherlands. Comparing this database with the data of EUROCAT in the Northern Netherlands showed that one-third of these congenital malformations (n = 229 in 217 children) were registered in both systems, while 99 (43%) were only registered by EUROCAT and 50 (22%) only by the nationwide database. It was possible to create a nationwide database, which can supplement the regional EUROCAT data with nationwide data on sixteen important diagnoses of congenital malformations.


GFP-expressing mammalian cells for fast, sensitive, noninvasive cell growth assessment in a kinetic mode.
This study correlates the fluorescent signal from stable recombinant CHO cell lines expressing the green fluorescent protein (GFP) at high levels with biomass or cell number, extending the use of fluorescent proteins to applications and assays where cell growth rates are important. Using a standard fluorometer, growth of these cells can be quantified noninvasively in multiwell plates, and because signals are obtained without preparation, the same culture samples can be measured repeatedly. Even with a small relative change in biomass, the specific growth rate can be determined in a few hours. The dynamics of cell populations can now be studied with high sensitivity, low error rate, and minimum sample preparation.


Does social disadvantage contribute to the excess mortality in rheumatoid arthritis patients?
Socioeconomic deprivation is associated with increased mortality from cardiovascular causes and malignancy. The influence of disadvantage in patients with rheumatoid arthritis (RA), who are known to have premature mortality, has not been ascertained. To assess the relation between the level of patient deprivation and mortality in RA patients. 200 RA patients, enrolled in a study comparing sulfasalazine and penicillamine in 1984-85, have been followed up prospectively for 12 years. Subjects were categorised into Carstairs groups with deprivation scores ranging from 1 (most affluent) to 7 (most deprived). Information about deaths was obtained from the Registrar General in Scotland, death certificates and GP/hospital records. There were more RA patients in the deprived areas then expected compared with the West of Scotland and England and Wales. Some 47.5% of the RA patients had died by 12 years-the majority of cardiorespiratory causes or malignancy. There were no differences in the median age or disease duration in the various Carstairs groups at study entry, but the percentage of deaths was higher in the more deprived groups after 12 years (36% dead in most affluent area compared with 61% in the most deprived, that is, in groups 6 and 7). In patients with RA increasing deprivation was associated with premature mortality. If confirmed elsewhere these findings have implications for rheumatological management strategies, for researchers involved in collaborative studies of patients from different socioeconomic backgrounds and for resource allocation.


Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption.
The role of different types of alcoholic beverage on cancer of the upper digestive tract was investigated in a case-control study conducted in the northern part of Italy on 305 male cases of cancer of the oral cavity and pharynx, 288 of oesophageal cancer and 1621 controls admitted to hospital for acute, non-neoplastic conditions, unrelated to alcohol intake. Similar significant trends of risk increase with increasing alcohol intake were seen for cancers of the oral cavity, pharynx and oesophagus independent of type (or types) of beverage consumed. Among the heaviest drinkers (i.e. greater than or equal to 84 drinks/week) odds ratios (ORs) of cancer of the oral cavity and pharynx for wine only, wine and spirits, and combination of wine, spirits, and beer were 11.2, 9.9 and 4.1, respectively. Corresponding oesophageal cancer ORs were 15.0, 10.0 and 6.0. This study from an area with high wine consumption confirms that wine per se can greatly enhance the risk of cancer of the upper digestive tract and suggests that the most frequently used alcoholic beverage in each study appears to be the most important determinant of these tumours.


Ensilication Improves the Thermal Stability of the Tuberculosis Antigen Ag85b and an Sbi-Ag85b Vaccine Conjugate.
There is an urgent need for the development of vaccine thermostabilisation methodologies as the maintenance of a continuous and reliable cold chain remains a major hurdle to the global distribution of safe and effective vaccines. Ensilication, a method that encases proteins in a resistant silica cage has been shown to physically prevent the thermal denaturation of a number of model proteins. In this study we investigate the utility of this promising approach in improving the thermal stability of antigens and vaccine conjugates highly relevant to the development of candidate tuberculosis vaccines, including antigen 85b conjugated with the Staphylococcus aureus-protein based adjuvant Sbi. Here we analyse the sensitivity of these constructs to thermal denaturation and demonstrate for the first time the benefits of ensilication in conferring these vaccine-relevant proteins with protection against temperature-induced loss of structure and function without the need for refrigeration. Our results reveal the potential of ensilication in facilitating the storage and transport of vaccines at ambient temperatures in the future and therefore in delivering life-saving vaccines globally, and in particular to remote areas of developing countries where disease rates are often highest.


TLR2 Expression on Select Lymphocyte Subsets as a New Marker in Glomerulonephritis.
Toll-like receptor (TLR) signaling may be involved in autoimmune kidney disorders and has been implicated in proliferative and non-proliferative glomerulonephritis (PGN and NPGN). In this study, we investigated the expression of TLR2 on T and B lymphocytes in relation to selected clinical parameters in patients with PGN and NPGN. We collected peripheral blood from the ulnar vein of patients with PGN (n = 15) or NPGN (n = 22) and healthy volunteers (n = 20). The percentage of peripheral blood mononuclear cells expressing TLR2 was determined with flow cytometry. TLR2 expression on T and B lymphocytes was increased in PGN patients compared with NPGN patients and controls (p ≤ 0.001). In patients with PGN, TLR2 expression correlated negatively with the serum concentrations of IgG and albumin and positively with urine protein excretion. Receiver operating characteristic (ROC) analysis indicated that TLR2 expression is a highly specific marker to distinguish PGN patients from NPGN patients and controls, especially on CD4+ T lymphocytes. Its use as a non-invasive marker of disease should be further investigated.


Metabolites of Trichoderma species isolated from damp building materials.
Buildings that have been flooded often have high concentrations of Trichoderma spores in the air while drying. Inhaled spores and spore and mycelial fragments contain large amounts of fungal glucan and natural products that contribute to the symptoms associated with indoor mould exposures. In this study, we considered both small molecules and peptaibol profiles of T. atroviride, T. koningiopsis, T. citrinoviride, and T. harzianum strains obtained from damp buildings in eastern Canada. Twenty-residue peptaibols and sorbicillin-derived metabolites (1-6) including a new structure, (R)-vertinolide (1), were characterized from T. citrinoviride. Trichoderma koningiopsis produced several koninginins (7-10), trikoningin KA V, and the 11-residue lipopeptaibols trikoningin KB I and trikoningin KB II. Trichoderma atroviride biosynthesized a mixture of 19-residue trichorzianine-like peptaibols, whereas T. harzianum produced 18-residue trichokindin-like peptaibols and the 11-residue harzianin HB I that was subsequently identified from the studied T. citrinoviride strain. Two α-pyrones, 6-pentyl-pyran-2-one (11) and an oxidized analog (12), were produced by both T. atroviride and T. harzianum. Aside from exposure to low molecular weight natural products, inhalation of Trichoderma spores and mycelial fragments may result in exposure to membrane-disrupting peptaibols. This investigation contributes to a more comprehensive understanding of the biologically active natural products produced by fungi commonly found in damp buildings.


New insights into the structure of PAMAM dendrimer/gold nanoparticle nanocomposites.
In this work, we have employed a suite of complementary analytical techniques to shed light on the nanocomposite structures formed during gold nanoparticles (AuNPs) synthesis in the presence of poly(amidoamine) (PAMAM) dendrimers. Nanocomposites of AuNPs and either fourth or eighth generation amine-terminated PAMAM dendrimers (G4 or G8) were prepared. The size distributions of AuNPs and the nanocomposites were determined by transmission electron microscopy. Atomic force microscopy phase imaging and neutral impact collision ion scattering spectroscopy (NICISS) were utilized for the first time to investigate and compare nanocomposite structures formed from G4 and G8. Our results suggest that G4 stabilized the AuNP by capping the AuNP particle surface but that a certain fraction of the gold surface was still barely covered. In contrast, the metal nanoparticle surface was completely covered by G8. In addition, NICISS results provided evidence that nanocomposites deformed when being deposited directly onto a substrate.


Diverse Short-Term Dynamics of Inhibitory Synapses Converging on Striatal Projection Neurons: Differential Changes in a Rodent Model of Parkinson's Disease.
Most neurons in the striatum are projection neurons (SPNs) which make synapses with each other within distances of approximately 100 µm. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP) between fast-spiking (FS) interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing), in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings.


Measurement of gastric residual volume: state of the science.
This literature review substantiates that there is confusion regarding what constitutes excessive gastric residual volume in adult tube-fed patients. Only one research study regarding gastric residuals was located; it indicated that 200 ml for a nasogastric tube and 100 ml for a gastrostomy tube should cause concern. The implications of these findings for adult-health nurses are discussed.


A membrane-bound flavocytochrome c-sulfide dehydrogenase from the purple phototrophic sulfur bacterium Ectothiorhodospira vacuolata.
The amino acid sequence of Ectothiorhodospira vacuolata cytochrome c-552, isolated from membranes with n-butanol, shows that it is a protein of 77 amino acid residues with a molecular mass of 9,041 Da. It is closely related to the cytochrome subunit of Chlorobium limicola f. sp. thiosulfatophilum flavocytochrome c-sulfide dehydrogenase (FCSD), having 49% identity. These data allowed isolation of a 5.5-kb subgenomic clone which contains the cytochrome gene and an adjacent flavoprotein gene as in other species which have an FCSD. The cytochrome subunit has a signal peptide with a normal cleavage site, but the flavoprotein subunit has a signal sequence which suggests that the mature protein has an N-terminal cysteine, characteristic of a diacyl glycerol-modified lipoprotein. The membrane localization of FCSD was confirmed by Western blotting with antibodies raised against Chromatium vinosum FCSD. When aligned according to the three-dimensional structure of Chromatium FCSD, all but one of the side chains near the flavin are conserved. These include the Cys 42 flavin adenine dinucleotide binding site; the Cys 161-Cys 337 disulfide; Glu 167, which modulates the reactivity with sulfite; and aromatic residues which may function as charge transfer acceptors from the flavin-sulfite adduct (C. vinosum numbering). The genetic context of FCSD is different from that in other species in that flanking genes are not conserved. The transcript is only large enough to encode the two FCSD subunits. Furthermore, Northern hybridization showed that the production of E. vacuolata FCSD mRNA is regulated by sulfide. All cultures that contained sulfide in the medium had elevated levels of FCSD RNA compared with cells grown on organics (acetate, malate, or succinate) or thiosulfate alone, consistent with the role of FCSD in sulfide oxidation.


A mesoporous NNN-pincer-based metal-organic framework scaffold for the preparation of noble-metal-free catalysts.
Through topology-guided synthesis, a Zr-based mesoporous MOF was successfully constructed, adopting a β-cristobalite-type structure. The MOF is embedded with well-arranged terpyridine coordination sites for facile post-synthetic metalation, and can be effectively used as a general scaffold for the preparation of noble-metal-free catalysts. For instance, the scaffolded metal@MOF material exhibits highly efficient catalytic activity for alkene epoxidation and arene borylation.


Investigation of protective effect of ellagic acid in phthalates-induced reproductive damage.
Phthalates that people are exposed to every day are toxic carcinogenic chemicals with proven harmful effects on growth and reproduction. Ellagic acid (EA) is a polyphenol derivative known for its antioxidant properties. We hypothesized that the possible reproductive damage mechanism of phthalates is oxidative attack and ellagic acid could have a protective effect against radical forms in the body through its antioxidant properties. Thirty-two male rats were randomly divided into 4 groups, with 8 rats in each. Phthalate (DBP) was administered intraperitoneally and EA acid through gastric oral gavage (phthalate group 500 mg/kg/day DBP; EA group 2 mg/kg/day ellagic acid; the treatment group 500 mg/kg/day DBP and 2 mg/kg/day EA). The vehicle of DBP and EA, carboxymethyl cellulose was administered to control group. At the end of 4 weeks the testis tissue samples were taken under mild anesthesia. Tissue malondialdehyde, antioxidant parameters, sperm motility, sperm density and abnormal spermatozoon ratios were determined. Analysis was performed with One Way ANOVA test using SPSS 12.0 program. As a result; it has been shown that DBP causes oxidative damage by increasing the malondialdehyde level and decreasing antioxidant parameters, increased abnormal sperm rate and decreased sperm motility and concentration and histopathological damage so this damage is inhibited by the antioxidant activity of ellagic acid.


DoctorEye: A multifunctional open platform for fast annotation and visualization of tumors in medical images.
This paper describes a flexible and easy-to-use annotation platform (GUI) for quick and precise identification and delineation of tumors in medical images. The design of the platform is clinically driven in order to ensure that the clinician can efficiently and intuitively annotate large number of 3D tomographic datasets. Both manual and well-known semiautomatic segmentation techniques are available in the platform allowing clinician to annotate multiple regions of interest at the same session. Additionally, it includes contour drawing, refinement and labeling tools that can effectively assist in the delineation of tumors. Furthermore, segmented tumor regions can be annotated, labeled, deleted, added and redefined. The platform has been tested over several MRI datasets to assess usability, extensibility and robustness with promising results.


Management of recurrent pacemaker-related bacteraemia with small colony variant Staphylococcus aureus in a haemodialysis patient.
A patient with chronic haemodialysis with a cardiac pacemaker was admitted for five episodes of bacteraemia with Staphylococcus during an 8-month period. The species identification was complicated since the morphological characters and biochemical reactions were unusual and differing. Molecular biological identification and typing methods revealed that the pathogens for all the episodes were the same strain of Staphylococcus aureus that had small colony variant characteristics. Continuous suppressive antibiotic treatment initiated after the last infection episode has been able to keep the patient free of bacteraemia relapse during the past 24 months without removing the pacemaker.


Maternal and foetal outcome of pregnant patients with sickle cell anaemia at Kenyatta National Hospital Nairobi. A retrospective study.
In a retrospective study we assessed pregnancy outcome in relation to sickle haemoglobin (HbS) and anaemia at Kenyatta National Hospital, Nairobi (KNH) from 1981-1986. There were 36% maternal and 45% foetal losses in sickle cell disease (SCD) pregnants and 7% foetal losses in sickle cell trait (HbAS) from 26 HbS-related pregnancies. 11 had homozygous sickle cell (SS) disease and 15 had HbAS. Age ranges for both groups were comparable. Mean haemoglobin-level for SS disease patients was 7.8 gm/dl (SD +/- 1.68), for AS patients 7.8 gm/dl (SD +/- 2.1). These maternal and foetal losses are quite high. Anaemia alone does not satisfactorily account for the higher losses in SS pregnancies. Other contributory factors need elucidation and intervention.


Debate: Are Stimulant Medications for Attention-Deficit/Hyperactivity Disorder Effective in the Long Term? (For).
Long-term effectiveness studies for ADHD medications are complicated to design well, and no single study design will capture the entire picture. Although randomized controlled trials are the highest level of evidence, most authorities agree that, when you have treatments as efficacious as the ADHD medications (methylphenidate and amphetamine derivatives and prodrugs, atomoxetine, guanfacine, and clonidine), it is neither practical nor ethical to conduct long-term placebo-controlled RCTs. As a consequence, almost all of the RCT evidence for ADHD medications relates to short-term studies. Although these provide strong evidence for short-term efficacy,1 they do not speak to long-term effectiveness. The European Medicines Agency (EMA) recognized the need for additional evidence of long-term effects before granting licenses for medications that will usually be required to be taken for several years. They therefore introduced a requirement for companies to demonstrate longer-term efficacy. This has generally been done through the use of randomized withdrawal designs that are designed to demonstrate continued efficacy over a period of 6 to 12 months. Several of these have been completed and published, all of which, as expected, demonstrate continued efficacy.2 The EMA also insisted that all new ADHD medications demonstrate continued effectiveness, and that adverse effects and safety be assessed up to 2 years. Again the studies completed so far support continued effectiveness, and, although highlighting the presence of common, expected adverse effects, have not identified any new safety signals or unexpected problems in targeted areas such as growth and cognition.3.


The influence of grass silage-to-maize silage ratio and concentrate composition on methane emissions, performance and milk composition of dairy cows.
It is well-established that altering the proportion of starch and fibre in ruminant diets can alter ruminal and post-ruminal digestion, although quantitative evidence that this reduces enteric methane (CH4) production in dairy cattle is lacking. The objective of this study was to examine the effect of varying grass-to-maize silage ratio (70 : 30 and 30 : 70 DM basis), offered ad libitum, with either a concentrate that was high in starch or fibre, on CH4 production, intake, performance and milk composition of dairy cows. A total of 20 cows were allocated to one of the four experimental diets in a two-by-two factorial design run as a Latin square with each period lasting 28 days. Measurements were conducted during the final 7 days of each period. Cows offered the high maize silage ration had a higher dry matter intake (DMI), milk yield, milk energy output and lower CH4 emissions when expressed per kg DMI and per unit of ingested gross energy, but there was no difference in total CH4 production. Several of the milk long-chain fatty acids (FA) were affected by forage treatment with the most notable being an increase in 18:0, 18:1 c9, 18:2 c9 c12 and total mono unsaturated FA, observed in cows offered the higher inclusion of maize silage, and an increase in 18:3 c9 c12 c15 when offered the higher grass silage ration. Varying the composition of the concentrate had no effect on DMI or milk production; however, when the high-starch concentrate was fed, milk protein concentration and milk FAs, 10:0, 14:1, 15:0, 16:1, increased and 18:0 decreased. Interactions were observed for milk fat concentration, being lower in cows offered high-grass silage and high-fibre concentrates compared with the high-starch concentrate, and FA 17:0, which was the highest in milk from cows fed the high-grass silage diet supplemented with the high-starch concentrate. In conclusion, increasing the proportion of maize silage in the diets of dairy cows increased intake and performance, and reduced CH4 production, but only when expressed on a DM or energy intake basis, whereas starch-to-fibre ratio in the concentrate had little effect on performance or CH4 production.


Estrogen suppression in males: metabolic effects.
We have shown that testosterone (T) deficiency per se is associated with marked catabolic effects on protein, calcium metabolism, and body composition in men independent of changes in GH or insulin-like growth factor I production. It is not clear,,however, whether estrogens have a major role in whole body anabolism in males. We investigated the metabolic effects of selective estrogen suppression in the male using a potent aromatase inhibitor, Arimidex (Anastrozole). First, a dose-response study of 12 males (mean age, 16.1 +/- 0.3 yr) was conducted, and blood withdrawn at baseline and after 10 days of oral Arimidex given as two different doses (either 0.5 or 1 mg) in random order with a 14-day washout in between. A sensitive estradiol (E2) assay showed an approximately 50% decrease in E2 concentrations with either of the two doses; hence, a 1-mg dose was selected for other studies. Subsequently, eight males (aged 15-22 yr; four adults and four late pubertal) had isotopic infusions of [(13)C]leucine and (42)Ca/(44)Ca, indirect calorimetry, dual energy x-ray absorptiometry, isokinetic dynamometry, and growth factors measurements performed before and after 10 weeks of daily doses of Arimidex. Contrary to the effects of T withdrawal, there were no significant changes in body composition (body mass index, fat mass, and fat-free mass) after estrogen suppression or in rates of protein synthesis or degradation; carbohydrate, lipid, or protein oxidation; muscle strength; calcium kinetics; or bone growth factors concentrations. However, E2 concentrations decreased 48% (P = 0.006), with no significant change in mean and peak GH concentrations, but with an 18% decrease in plasma insulin-like growth factor I concentrations. There was a 58% increase in serum T (P = 0.0001), sex hormone-binding globulin did not change, whereas LH and FSH concentrations increased (P < 0.02, both). Serum bone markers, osteocalcin and bone alkaline phosphatase concentrations, and rates of bone calcium deposition and resorption did not change. In conclusion, these data suggest that in the male 1) estrogens do not contribute significantly to the changes in body composition and protein synthesis observed with changing androgen levels; 2) estrogen is a main regulator of the gonadal-pituitary feedback for the gonadotropin axis; and 3) this level of aromatase inhibition does not negatively impact either kinetically measured rates of bone calcium turnover or indirect markers of bone calcium turnover, at least in the short term. Further studies will provide valuable information on whether timed aromatase inhibition can be useful in increasing the height potential of pubertal boys with profound growth retardation without the confounding negative effects of gonadal androgen suppression.


PBC68: a nuclear pore complex protein that associates reversibly with the mitotic spindle.
Using autoimmune antibodies from a patient with primary biliary cirrhosis we have identified a 68 kDa nuclear envelope protein, termed PBC68. This protein is co-precipitated with a 98 kDa and a 250 kDa polypeptide and is distinct from the nuclear lamins. Immunostaining of digitonin-permeabilized cells indicates that PBC68 is restricted to the inner (nucleoplasmic) face of the nuclear envelope, while indirect immunofluorescence and immunoelectron microscopy show that PBC68 is located on fibrillar structures emanating from the nuclear pore complex. The autoantigen is modified at early prophase and disassembles at prometaphase concurrently with the breakdown of the nuclear envelope. The disassembled material, instead of diffusing throughout the cytoplasm as other nucleoporins, is targeted to the mitotic spindle and remains stably bound to it until anaphase. At telophase PBC68 is released from the mitotic apparatus and reassembles late, after incorporation of LAP2B and B-type lamins, onto the reforming nuclear envelope. The partitioning of PBC68 in dividing cells supports the notion that subsets of nuclear envelope proteins are actively sorted during mitosis by transiently anchoring to spindle microtubules. Furthermore, the data suggest that specific constituents of pore complex are released in a stepwise fashion from their anchorage sites before becoming available for nuclear reassembly.


"If You Don't Have the Heart to Help, You Cannot Do This Job": The Multidimensional Wellbeing of Community Health Workers Serving Refugees During the COVID-19 Pandemic.
Community health workers are members of two groups whose short- and long-term health has been uniquely shaped by the COVID-19 pandemic: health workers and the oft-marginalized populations that they serve. Yet, their wellbeing, particularly of those serving resettled refugees, before and during the pandemic has been largely overlooked. Drawing from a holistic conceptualization of wellness, this study examined the effects of the COVID-19 pandemic on a group of cultural health navigators (CHNs), who serve resettled refugees. We conducted semi-structured individual interviews with CHNs at a southwestern U.S. hospital system between July and August 2020, a critical time in the pandemic. Our analysis produced four themes that encapsulate the effects of the pandemic on CHN wellbeing: (1) "You fear for your life": Chronic risk of COVID-19 exposure takes a toll on physical, emotional, and environmental wellbeing; (2) "It is stressful because it is completely new": Uncertainty diminishes occupational, financial, and emotional wellbeing; (3) "If you don't have the heart to help, you cannot do this job": CHNs remain committed while facing challenges to their occupational wellbeing on multiple fronts; and (4) "Now, you cannot release your stress": Loss of and shifts in outlets integral to social and spiritual wellbeing. The findings deepen empirical understanding of how the pandemic affected the holistic wellbeing of CHNs, as they continued to serve their communities in a time of crisis. We discuss the implications for addressing the multidimensionality of community health worker wellbeing in research, policy, and practice.


The role of the Ah locus in hexachlorobenzene-induced porphyria. Studies in congenic C57BL/6J mice.
The role of the Ah locus in hexachlorobenzene (HCB)-induced porphyria and the possible involvement of P-450 cytochromes P(1)450 and P(3)450 in the pathogenesis of this disease were investigated in two congenic strains of C57BL/6J mice that differ only at this locus. Female B6-Ahb mice (Ah receptor: approximately 30-70 fmol/mg of cytosolic protein) and B6-Ahd mice (Ah receptor: undetectable) were pretreated with iron (500 mg/kg) and then fed a diet containing 0 or 200 p.p.m. of HCB for up to 17 weeks. Mice from the two strains consumed similar amounts of HCB. Urinary excretion of porphyrins was increased after 7 weeks of HCB treatment in B6-Ahb mice, and after 15 weeks was over 200 times greater than that of mice given iron only. In B6-Ahd mice, porphyrin excretion did not begin to increase until after 13 weeks, and after 15 weeks was only six times greater than that of controls. Similar differences were seen in the 15-week hepatic porphyrin concentrations (B6-Ahb: 1110 +/- 393; B6-Ahd: 17.6 +/- 14.5; controls: approximately 0.20 nmol/g). Uroporphyrinogen decarboxylase (EC 184.108.40.206) activity was diminished by 70 and 20% in B6-Ahb B6-Ahd mice respectively after 15 weeks of treatment with HCB. Cytochromes P(1)450 and P(3)450 were measured in hepatic microsomes (microsomal fractions) by radioimmunoassay and immunoblotting, using antisera raised against the orthologous rat isoenzymes P450c and P450d. HCB induced small amounts of a protein recognized by anti-P450c (P(1)450) in B6-Ahd mice, but not in B6-Ahd mice. Relatively large amounts of a protein recognized by anti-P450d (P(3)450) were induced in both strains, but to a somewhat greater extent in the B6-Ahb mice. The hepatic accumulation of HCB at 15 weeks was greater in B6-Ahb than in B6-Ahd mice, in association with elevated hepatic lipid levels in the former strain. The results of this experiment indicate that the Ah locus influences the susceptibility of C57BL/6J mice to HCB-induced porphyria and are consistent with the suggestion that the sustained induction of P(3)450 and/or P(1)450 may be a causative factor in the development of this disease.


Effects of All-Atom Molecular Mechanics Force Fields on Amyloid Peptide Assembly: The Case of Aβ16-22 Dimer.
We investigated the effects of 17 widely used atomistic molecular mechanics force fields (MMFFs) on the structures and kinetics of amyloid peptide assembly. To this end, we performed large-scale all-atom molecular dynamics simulations in explicit water on the dimer of the seven-residue fragment of the Alzheimer's amyloid-β peptide, Aβ16-22, for a total time of 0.34 ms. We compared the effects of these MMFFs by analyzing various global reaction coordinates, secondary structure contents, the fibril population, the in-register and out-of-register architectures, and the fibril formation time at 310 K. While the AMBER94, AMBER99, and AMBER12SB force fields do not predict any β-sheets, the seven force fields, AMBER96, GROMOS45a3, GROMOS53a5, GROMOS53a6, GROMOS43a1, GROMOS43a2, and GROMOS54a7, form β-sheets rapidly. In contrast, the following five force fields, AMBER99-ILDN, AMBER14SB, CHARMM22*, CHARMM36, and CHARMM36m, are the best candidates for studying amyloid peptide assembly, as they provide good balances in terms of structures and kinetics. We also investigated the assembly mechanisms of dimeric Aβ16-22 and found that the fibril formation rate is predominantly controlled by the total β-strand content.


Interventions across the retirement transition for improving well-being: a scoping review protocol.
The work-to-retirement transition involves a process of psychologically and behaviourally distancing oneself from the workforce that is often accompanied by other social changes. The person is confronted with new social roles, expectations, challenges and opportunities that can influence lifestyle and well-being. In the scientific literature, we find recent reports of interventions aimed at improving health and well-being in people at retirement age. However, there is still a gap of knowledge on how different interventions during retirement might improve health status. We intend to conduct a scoping review with the aim of describing interventions for improving well-being across the retirement transition. The methodological framework described by Arksey and O'Malley; the Joanna Briggs Institute guidelines as well as the Preferred Reporting Items for scoping reviews and Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols statements will be followed. Eligibility criteria comprise of: (a) all type of original studies, review articles or reports published on journals as well as grey literature; (b) describing interventions to improve the well-being in adults across their retirement transition; (c) including participants before, during and after retirement; (d) all publications must describe variables associated with participants' physical and/or psychological and/or social well-being and/or perceived quality of life related to these; (e) no language restriction and (f) published from January 2000 to March 2019. The main findings will be summarised using a narrative descriptive synthesis approach and grouped following the population, concept and context principles. A stakeholder meeting will be held to provide feedback on the findings and to develop next steps in research and practice. Approval from a research ethics committee is not required, as no personal information will be collected. We plan to disseminate our research findings at different levels: scientific community, clinical and social arenas, as well as to healthcare leaders and policymakers and general population. The project has been registered at Open Science Framework with the name TRANSITS: work to retirement transition project.


Measuring Progress on the Control of Porcine Reproductive and Respiratory Syndrome (PRRS) at a Regional Level: The Minnesota N212 Regional Control Project (Rcp) as a Working Example.
Due to the highly transmissible nature of porcine reproductive and respiratory syndrome (PRRS), implementation of regional programs to control the disease may be critical. Because PRRS is not reported in the US, numerous voluntary regional control projects (RCPs) have been established. However, the effect of RCPs on PRRS control has not been assessed yet. This study aims to quantify the extent to which RCPs contribute to PRRS control by proposing a methodological framework to evaluate the progress of RCPs. Information collected between July 2012 and June 2015 from the Minnesota Voluntary Regional PRRS Elimination Project (RCP-N212) was used. Demography of premises (e.g. composition of farms with sows = SS and without sows = NSS) was assessed by a repeated analysis of variance. By using general linear mixed-effects models, active participation of farms enrolled in the RCP-N212, defined as the decision to share (or not to share) PRRS status, was evaluated and used as a predictor, along with other variables, to assess the PRRS trend over time. Additionally, spatial and temporal patterns of farmers' participation and the disease dynamics were investigated. The number of farms enrolled in RCP-N212 and its geographical coverage increased, but the proportion of SS and NSS did not vary significantly over time. A significant increasing (p<0.001) trend in farmers' decision to share PRRS status was observed, but with NSS producers less willing to report and a large variability between counties. The incidence of PRRS significantly (p<0.001) decreased, showing a negative correlation between degree of participation and occurrence of PRRS (p<0.001) and a positive correlation with farm density at the county level (p = 0.02). Despite a noted decrease in PRRS, significant spatio-temporal patterns of incidence of the disease over 3-weeks and 3-kms during the entire study period were identified. This study established a systematic approach to quantify the effect of RCPs on PRRS control. Despite an increase in number of farms enrolled in the RCP-N212, active participation is not ensured. By evaluating the effect of participation on the occurrence of PRRS, the value of sharing information among producers may be demonstrated, in turn justifying the existence of RCPs.


KIF21A Gene c.2860C>T Mutation in CFEOM1A: The First Report from Iran.
Congenital Fibrosis of the Extra Ocular Muscles1 (CFEOM1) is an autosomal dominant condition, caused by mutation in the KIF21A and TUBB3. It is characterized by congenital non-progressive restrictive ophthalmoplegia and ptosis. Mutational analysis of the known genes in such rare diseases by Sanger sequencing not only prevents wasting the time and expenses but also speeds diagnosis process, genetic counseling, and the possibility of prenatal diagnosis. Here, for the first time, association of pathogenic variant c.2860C>T in KIF21A gene in an Iranian family with positive history of CFEO-M1A was reported.


Residential Segregation and Overweight/Obesity Among African-American Adults: A Critical Review.
The relationship between residential segregation and overweight/obesity among African-American adults remains unclear. Elucidating that relationship is relevant to efforts to prevent and to reduce racial disparities in obesity. This article provides a critical review of the 11 empirical studies of segregation and overweight/obesity among African-American adults. Results revealed that most studies did not use a valid measure of segregation, many did not use a valid measure of overweight/obesity, and many did not control for neighborhood poverty. Only four (36% of the) studies used valid measures of both segregation and overweight/obesity and also controlled for area-poverty. Those four studies suggest that segregation contributes to overweight and obesity among African-American adults, but that conclusion cannot be drawn with certainty in light of the considerable methodologic problems in this area of research. Suggestions for improving research on this topic are provided.


Why do patients decline participation in offered pulmonary rehabilitation? A qualitative study.
The purpose of this study is to produce insight in the explanations for declining pulmonary rehabilitation given by patients with chronic obstructive pulmonary disease. The participants were recruited from a hospital in Denmark, among patients hospitalized due to an exacerbation of chronic obstructive pulmonary disease and among stable patients attending an outpatient clinic. Patients who decline participation in offered pulmonary rehabilitation, who speak Danish, who are able to give informed consent and to participate in a 1-hour interview. The research question was answered through interviews with 19 patients. The interviews were recorded and transcribed verbatim. The transcripts were analyzed using inductive content analysis. The transcripts were condensed; categories were developed providing different types of explanations for declining pulmonary rehabilitation. Each category was named using a content characteristic word. This study shows that some patients do not remember or recall that they have been offered pulmonary rehabilitation during hospitalization. Especially the oldest patients perceive themselves to be too frail from chronic obstructive pulmonary disease, comorbidity or multimorbidity. The male patients tend to find pulmonary rehabilitation irrelevant because they do not consider themselves ill. Furthermore, the study shows that pulmonary rehabilitation is perceived to be time-consuming and conflicting with daily activities. Patients decline pulmonary rehabilitation because the intervention does not fit their perception of health and because they find that participation in the program may collide with priorities and daily activities.


Vascularized composite tissue transfers or open fractures with massive soft-tissue defects in the lower extremities.
From 1982 to 1998, we treated 39 patients with type IIIB and IIIC fractures in the lower extremities by vascularized composite tissue transfers. Thirty-four of the lesions affected the lower leg, and 5 the foot and ankle. The peroneal flap was used in 25 cases, the latissimus dorsi musculocutaneous flap in 12, the scapula flap in 1, and the gracilis muscle flap in 1. In cases with a peroneal flap transfer, 18 cases used osteocutaneous flap with a fibula. Postoperative circulatory disturbances resulted in revision surgery in 9 patients. Eventually, grafting was successful in 37 patients. In patients with a lower leg reconstruction, additional bone grafting was performed in 7 of 16 patients with cutaneous or musculocutaneous flap transfers. No patient with osteocutaneous flap transfers required an additional bone grafting. The mean periods between injury and time to bone union were 11.7 months in patients with cutaneous flap transfers, and 7.5 months in patients with osteocutaneous flap transfers.


Association of Low Umbilical Cord pH and Hypoglycemia in Healthy Term Newborns: Should it Be a Part of Postnatal Screening?
Hypoglycemia may lead to neurological impairment; therefore, high-risk newborns are screened postnatally. However, hypoglycemia monitoring protocols often do not include cord blood acidosis as a risk factor. The study aimed to find an association between asymptomatic cord blood acidosis and hypoglycemia. All healthy term infants born at McMaster Children Hospital, Hamilton, Canada, between October 2013 and September 2014, who had umbilical cord blood pH <7.0 or base excess <12 mmol/L were studied. Infants with evidence of hypoxic-ischemic encephalopathy, birth weights outside of 10th to 95th percentiles for gestation, mothers with preeclampsia, diabetes or taking a -blockers at the time of the birth were excluded. Hypoglycemia was defined as blood glucose <2.6 mmol/L in the first two hours of life. One hundred sixtysix infants met the cord blood gas criteria, but only 16 had hypoglycemia. Although infants with mild perinatal depression are at risk for hypoglycemia, a significant association could not be proved.


A near-infrared fluorescent probe for viscosity: Differentiating cancer cells from normal cells and dual-modal imaging in tumor mice.
As a basic parameter of the intracellular microenvironment, viscosity is closely related to the development of cancer. Thus, it is necessary to utilize a sensitive tool to visualize the viscosity in tumor cells and mice, which is helpful for the diagnosis of cancer. Herein, a novel dual-modal probe (IX-V) that has a near-infrared fluorescence (NIRF) and photoacoustic (PA) response to viscosity is synthesized. In low viscosity media, the probe has no fluorescence. With the increase of viscosity, the fluorescence is produced in the near-infrared region due to the inhibition of the TICT process. At the same time, the probe shows different photoacoustic (PA) signals in different viscosity media. Most notably, the viscosity in tumor cells has been imaged successfully by the application of IX-V, and the probe can effectively distinguish cancer cells from normal cells co-cultured in one dish by the difference of fluorescence intensity. In addition, the probe has been used for dual-modal imaging (NIRF and PA) of viscosity in tumor mice, which provides a tool for exploring the relationship between viscosity and diseases. That is to say, IX-V can achieve complementary imaging effects and has great application prospects in the tumor diagnosis.


Information Challenges Associated With Accessing and Sharing of Patient Information in Disasters: A Qualitative Analysis.
As disasters increase in frequency and severity, so too does the health impact on affected populations. Disasters exacerbate the already challenging health information-sharing landscape. A reduced capacity to access and share patient information may have negative impacts on providers' ability to care for patients individually and to address disaster health outcomes at the population level. Between October 2018 and July 2019, we conducted 21 semistructured interviews with physicians experienced in providing healthcare during disasters to understand the challenges related to patient information sharing in disaster responses. Key informants noted challenges with patient information management-including accessing, sharing, and transferring information-and that it was a barrier to providing effective clinical care in disasters. Three major areas were identified as challenges: (1) lack of systematic mechanisms for patient information sharing during disaster handoffs, (2) lack of access to a patient's past medical history, and (3) population-level impacts of patient information-sharing breakdowns in disasters. Reducing barriers to effective patient information sharing is a critical need during disasters. Requirements generally fall to overburdened clinicians, and novel solutions that ease this responsibility and leverage existing infrastructure should be explored. Work conducted during the COVID-19 pandemic may inform new solutions. Integrated approaches that support information sharing in real time will improve patient care at the individual level and can support operational improvements to current and future disaster responses.


Vibrational circular dichroism spectroscopy of a spin-triplet bis-(biuretato) cobaltate(III) coordination compound with low-lying electronic transitions.
Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy was applied in the analysis of vibrational and low lying electronic transitions of a triplet ground state cobalt(III) coordination compound. The spectroscopic measurements were performed on the tetrabutylammonium salt of (6S,7S)-1,3,5,8,10,12-hexaaza-2,4,9,11-tetraoxo-6,7-diphenyl-dodecanato(4-)cobaltate(III) in DMSO solution and in potassium bromide pellets. The chiral anion exhibits an unusual geometry for cobalt(III), being four-coordinate, planar, and paramagnetic with an intermediate spin state. The spectroscopic results were compared to measurements performed on the free ligand and to theoretical calculations using density functional theory (B3LYP/TZVP). The results of the VCD analysis of the coordination compound identified an electronic, dipole-forbidden, magnetic dipole-allowed low-lying d-d transition located in the mid infrared, as well as several amide stretch transitions located in the fingerprint region (1800-1100 cm(-1)), in both the liquid and solid phase. VCD signals were found to be 5-10 times higher than expected, indicating enhancement of the vibrational CD signals, caused by coupling of the vibrational transitions with the close-lying electronic transition.


Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia.
Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head-injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 +/- 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p less than 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF less than or equal to 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful.


[Reinfections and the development of schistosomal periportal fibrosis in the murine model].
Experimental pipestem fibrosis of the liver developed more frequently (69.2%) in mice submitted to repeated infections with Schistosoma mansoni, than with single infection (11.1%). The counting of eggs in the liver revealed no significant differences between the two experimental groups. Although the reason why multiple infections favor the development of pipestem fibrosis has not been elucidated, the data obtained represent an experimental support to clinico-epidemiological claims that repeated infections play a role in pathogenesis of hepatosplenic schistosomiasis


Correlated Sensory and Sympathetic Innervation Between the Acupoint BL23 and Kidney in the Rat.
Objective: To investigate the sensory and sympathetic innervations associated with both acupoint "Shenshu" (BL23) and kidney in the rat for insight into the neuronal correlation between the Back-Shu Point and its corresponding visceral organ. Methods: The BL23 and kidney were selected as the representative acupoint and visceral organ in this study, in which their local nerve fibers were examined by using double fluorescent immunohistochemistry with calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH). Meanwhile, their neuronal correlation in the dorsal root ganglia (DRGs), spinal cord, and sympathetic (paravertebral) chain were investigated using a double fluorescent neural tracing technique with Alexa Fluor 488 and 594 conjugates with cholera toxin subunit B (AF488/594-CTB). Results: The local tissue of acupoint BL23 and the fibrous capsule of kidney distributed abundantly with CGRP- and TH-positive nerve fibers, corresponding to their sensory and sympathetic innervation. On the other hand, the sensory neurons associated with acupoint BL23 and kidney were labeled with AF488/594-CTB and distributed from thoracic (T) 11 to lumbar (L) 3 DRGs and from T10 to L2 DRGs, respectively, in which some of them in T12-T13 DRGs were simultaneously labeled with both AF488/594-CTB. Also, postganglionic neurons associated with both acupoint BL23 and kidney were found in the sympathetic chain at the same spinal segments but separately labeled with AF488-CTB and AF594-CTB. Conclusion: Our study demonstrates the neural characteristics of the acupoint BL23 and kidney in the rat from the perspective of neurochemistry and neural pathways, providing an example for understanding the neuronal correlation between the Back-Shu Points and their corresponding visceral organs. These results suggest that the stimulation of the Back-Shu Points may regulate the activities of the target-organs via the periphery sensory and sympathetic pathways.


[Genetic polymorphisms and new perspectives in the prevention and treatment of obesity].
The prevalence of obesity has increased to an extraordinary degree, especially over the last three decades, so that if these trends persist, practically all of the adult population would be obese in the course of only two generations. On the basis of family and adoption studies, it has been estimated that the genetic component in obesity ranges from 20% to 80%. Thus, the most common forms of obesity would depend on the interaction of multiple genes as well as on the influence of various environmental factors, such as eating behaviour and lifestyle. Although none of these genes potentially involved in the control of body weight seems to be directly responsible for the syndrome, there have been reports of interesting associations between polymorphisms of certain candidate genes and obesity or its metabolic complications. The studies into associations between genotypes and obese phenotype have increased over the last few years and have basically focussed on the genes involved in the control of the energy balance, giving rise to a whole series of results which might constitute the basis for extremely interesting strategies for the prevention and treatment of this serious problem.


Subunit separation in reversed micelle system reveals the existence of active centers both on light and heavy gamma-glutamyltransferase subunits.
Regulation of supra-macromolecular composition and catalytic activity of a heterodimeric enzyme, gamma-glutamyltransferase, in the system of Aerosol OT (sodium bis(2-ethylhexyl) sulfosuccinate) reversed micelles in octane were studied. Variation of the surfactant hydration degree (parameter, determining dimensions of the polar inner cavity of the micelle) causes a reversible dissociation of the enzyme to light and heavy subunits. Both enzyme subunits possess catalytic activity. The light and heavy subunits of the enzyme were separated on a preparative scale in a reversed micelle system using ultracentrifugation. The active centers of gamma-glutamyltransferase were studied using its irreversible inhibitor--AT-125 (L-(alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid). Separation of the gamma-glutamyltransferase subunits results in the 'opening' of a new active center located at the heavy subunit. In the dimer form of the enzyme this center is masked and it is not accessible to both substrate and inhibitor molecules.


Intake of Food Supplements, Caffeine, Green Tea and Protein Products among Young Danish Men Training in Commercial Gyms for Increasing Muscle Mass.
Sixty-three men (15-35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects.