Cancer in The Netherlands. From scenarios to health policy.
Future scenarios on cancer in The Netherlands were made with the help of existing trends, demographic changes and expected developments in cancer research, prevention, screening and treatment. Until the year 2000, cancer incidence will probably increase by 1.5% per year, by nearly 3% per year and the need for health care facilities accordingly. Upon the request of Parliament, the Dutch government used this information to formulate a long-term cancer control policy. Faced with a restricted budget and a growing demand for care, the government plans to increase its efforts in the areas of prevention and screening and to improve the efficiency of cancer care. More attention will be paid to the quality of life of those patients who cannot be cured. Support for cancer research will be maintained at its present level.


Dscam mutation leads to hydrocephalus and decreased motor function.
The nervous system is one of the most complicated organ systems in invertebrates and vertebrates. Down syndrome cell adhesion molecule (DSCAM) of the immunoglobulin (Ig) superfamily is expressed widely in the nervous system during embryonic development. Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching, dendritic tiling and cell spacing. However, the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear. Here, we show that Dscam ( del17 ) mutant mice exhibit severe hydrocephalus, decreased motor function and impaired motor learning ability. Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.


Selected trace elements and metals in groundwater within Permian sediments near Olkusz (Zn-Pb ore mining region, S Poland).
The extensive mining of Zn-Pb ores in the Olkusz region resulted in significant changes of both water table level and chemical composition of water in all aquifers in the area. This was caused by intensive dewatering of mining excavations and development of a thick aeration zone reaching 150 m in a central part of the area. That created favorable conditions for oxidation of metal sulfides occurring in the ore-bearing dolomites (Middle Triassic) and started the process of forming readily soluble hydroxysulphates which then migrated to lower aquifers, including the Permian. As a result of those processes, various metals and other elements toxic to the water environment appeared in leaks observed in mine galleries. Changes in concentrations of selected elements (Fe, Mn, Zn, Pb, Cu, Ba, Ni, Co, As, Cr, Hg, Tl, Ag, Cd, B) in mine waters over the period of the last nearly 50 years were described. Water samples were collected from exploratory boreholes, piezometers, and wells located in investigated area inflows and seepages occurring in shafts and drifts excavated in Permian conglomerates. Mean concentrations of metals (Pb, Cd, Cr, Hg, Tl) and other toxic elements were surprisingly low; Pb, 3.94 μg/L; Cd, 0.2 μg/L; Cr, up to 2.26 μg/L; Hg, 0.25 μg/L; Tl, 3.59 μg/L; and As, 6.31 μg/L. However, the observed concentrations varied significantly over time, reaching respectively up to 190 μg Pb/L, 60 μg Cd/L, 15.6 μg Cr/L, 2.67 μg Hg/L, 81.3 μg Tl/L, and 155 μg As/L.


Brownfield land and health: A systematic review of the literature.
Brownfield land is vacant or derelict land that was previously used for industrial or commercial purposes. Brownfield land is increasingly being targeted for housing development, however, depending on the previous use and remediation activity, it might pose potential risks to the health of residents on or in the vicinity of redeveloped sites. This systematic review of the literature synthesises the empirical evidence on the associations between brownfield land and health. We systematically searched EMBASE, MEDLINE, Global Health, Web of Science, Scopus and GreenFile using a study protocol registered on PROSPERO (CRD42022286826). The search strategy combined the keywords "brownfield" and its interchangeable terms such as "previously developed land", and any health outcomes such as "respiratory diseases" and "mortality". Publications identified from the search were screened for eligibility by two authors, and data were extracted from the selected articles. Study quality was assessed based on the Newcastle-Ottawa Scale. Of the 1,987 records retrieved, 6 studies met the inclusion criteria; 3 ecological studies, 2 cross-sectional studies, and 1 longitudinal study. There was considerable heterogeneity in the exposure metrics and health outcomes assessed. All studies found significant positive associations between brownfield land proximity or density with at least one health relevant outcome, including poorer self-reported general health, increased mortality rates, increased birth defects, increased serum metal levels, and accelerated immune ageing. Brownfield land may negatively affect the health of nearby residents. The epidemiological evidence on health effects associated with brownfield land in local communities, however, remains inconclusive and limited. Further studies are required to build the evidence base to inform future housing policies and urban planning.


Determination of mitral valve area with echocardiography, using intra-operative 3-dimensional versus intra- & post-operative pressure half-time technique in mitral valve repair surgery.
We hypothesized that mitral valve areas (MVAs) with echocardiography, using 3D planimetry technique (measured at one point at maximal opening of mitral valve) versus pressure half-time technique (PHT, measured during entire diastolic phase) in mitral valve repair surgery (MVR) would be different. Patients who had undergone MVR were retrospectively reviewed, and two different observers measured the MVAs using PHT and 3D planimetry technique. The MVAs derived from recorded medical data, using PHT and 3D planimetry technique were abbreviated to MVA-PHT1 and MVA-3D1, and data from the PHT and 3D planimetry techniques by observer A and observer B were determined as MVA-PHT2 and MVA-3D2, and MVA-PHT3 and MVA-3D3, respectively. The MVA derived by post-operative transthoracic echocardiography using the PHT technique was determined as MVA-TTE. Intraclass correlation coefficients were 0.90 for the intra-operative PHT technique and 0.78 for the intra-operative 3D planimetry technique. MVA-3D1 (2.91 ± 0.65 cm2), MVA-3D2 (3.00 ± 0.63 cm2) and MVA-3D3 (2.97 ± 0.88 cm2) were significantly larger than MVA-TTE (2.40 ± 0.59 cm2), but intra-operative MVAs-PHT were not. The biases and precisions were larger, and the correlation coefficients were lower in 3D planimetry technique compared with PHT technique. MVA measured by 3D planimetry technique with TEE at the intra-operative post-MVR period was seemed to be larger than that measured by the PHT technique with TTE at the post-operative period. However, it did not mean that the 3D planimetry technique was inaccurate but needs cautions at determination of MVA using different techniques.


Tumor in undescended intrapelvic testis revealed by supraclavicular lymphadenopathy: a case report and literature review.
Testicular cancer is a rare disease. The incidence of testicular cancer in undescended testicles is of 3 to 48 times greater than in the general population. In the developed countries, the existence of undescended testicles in the adult population is rare, due to systematic practice of elective orchidopexy before the second year of life and orchiectomy in post adolescent males with undescended testicles. Despite these prevention measures, there are still some isolated cases of intra-abdominal testicular tumors in adults. We report a case of testicular cancer in cryptorchid testis revealed by supraclavicular lymphadenopathy. We report a case of a 46 year old fertile man with a history of unilateral cryptorchidism who presented with a palpable left supraclavicular mass and absence of the right testicle. On investigations an intrapelvic testis tumor was diagnosed. Laparotomy and complete excision was carried out. The possible association between the undescended testis and cancer transformations is briefly discussed. Testicular cancer in undescended testicles should not be ignored. Only early diagnosis and lower of testis in scrotumprevent such clinical forms.


Sentinel lymph node examination by frozen section in breast cancer patients.
Our study indicates that sentinel node analysis by frozen section at the time of primary surgical treatment for invasive breast cancer is a reasonable and prudent effort. No cost analysis study is projected in this paper, but the risk/benefit to the patient as well as cost savings would seem to be apparent and significant.


Tachyarrhythmia: Presenting symptom of cardiac tumour.
Cardiac arrhythmia in an apparently healthy heart needs a detailed anatomical investigation to detect any unsuspected anomalies such as cardiomyopathy and cardiac tumours. We report cardiac tumours as a cause of tachyarrhythmias. Cardiac tumours are rare in childhood and should be considered as part of the differential diagnosis in a child presenting with cardiac signs and symptoms and treatment should be individualised for each patient.


Effects of Communities That Care on Males' and Females' Drug Use and Delinquency 9 Years After Baseline in a Community-Randomized Trial.
This study tested sustained effects of the Communities That Care (CTC) prevention system on health-risking behaviors 9 years after baseline in a community-randomized trial involving 24 towns in seven states. Earlier analyses found sustained effects on abstinence from drug use and delinquency through Grade 12 in a panel of fifth graders. At age 19, 91 % (n = 3986) of the living panel completed the survey. Data were analyzed using generalized linear mixed models. The prevalence of lifetime and current substance use and delinquency were the primary outcomes. Secondary outcomes included substance use disorders, major depression, suicidality, educational attainment, and sexual risk behaviors. CTC had a significant overall effect across lifetime measures of the primary outcomes for males, but not for females or the full sample, although lifetime abstinence from delinquency in the full sample was significantly higher in CTC communities (ARR = 1.16). Males in CTC communities also continued to show greater lifetime abstinence from cigarette smoking (ARR = 1.22). CTC did not have a sustained effect on current substance use and delinquency nor did it improve the secondary outcomes at age 19 for either gender. Communities using CTC may need to extend their prevention planning to include the high school years to sustain effects on drug use and delinquency beyond high school for both genders. ClinicalTrials.gov identifier: NCT01088542.


Gas chromatographic relative retention data for pesticides on nine packed columns: II. Organophosphorus and organochlorine pesticides, using electron-capture detection.
The retention time relative to parathion, absolute retention time, concentration range, peak asymmetry factor, and peak shape class are given for each of 42 organophosphorus pesticides and 28 organochlorine pesticides analyzed by gas chromatography (GC) on 9 different packed columns. The packing materials used were 3% SP-2100, 1% Dexsil-300, 3% OV-17, 1.5% OV-17 + 1.95% QF-1, 4% SE-30 + 6% QF-1, 3% OV-17 + 3% OV-210, 5% DC-200 + 7.5% QF-1,3% Carbowax-20M, and 4% Reoplex-400. Retention data were determined at 200 degrees C with a carrier gas flow at uopt, using a 63Ni electron-capture detector. Results should be useful for preliminary identification of environmental samples and also for single or multiple pesticide residue analysis.


Chromatographic and Spectrophotometric Analysis of Phenolic Compounds from Fruits of Libidibia ferrea Martius.
Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz (Fabaceae) is a tree which is native to Brazil, widely known as "Jucá," where its herbal derivatives are used in folk medicine with several therapeutic properties. The constituents, which have already been described in the fruit, are mainly hydrolysable tannins (gallic acid [GA] and ellagic acid [EA]). The aim of this study was to investigate the phenolic variability in the fruit of L. ferrea by ultraviolet/visible (UV/VIS) and chromatographic methods (high-performance liquid chromatography [HPLC]/high-performance thin layer chromatography [HPTLC]). Several samples were collected from different regions of Brazil and the qualitative (fingerprints by HPTLC and HPLC) and quantitative analysis (UV/VIS and HPLC) of polyphenols were performed. The HPTLC and HPLC profiles allowed separation and identification of both major analytical markers: EA and GA. The chemical profiles were similar in a number of spots or peaks for the samples, but some differences could be observed in the intensity or area of the analytical markers for HPTLC or HPLC, respectively. Regarding the quantitative analysis, the polyphenolic content by UV/VIS ranged from 13.99 to 37.86 g% expressed as GA or from 10.75 to 29.09 g% expressed as EA. The contents of EA and GA by liquid chromatography-reversed phase (LC-RP) method ranged from 0.57 to 2.68 g% and from 0.54 to 3.23 g%, respectively. The chemical profiles obtained by HPTLC or HPLC, as well as the quantitative analysis by spectrophotometry or LC-RP method, were suitable for discrimination of each herbal sample and can be used as tools for the comparative analysis of the fruits from L. ferrea. The polyphenols of fruits of Libidibia ferrea can be quantified by UV/VIS and HPLCThe HPLC method was able to detect the gallic and ellagic acids in several samples of fruits of Libidibia ferreaThe phenolic profiles of fruits from Libidibia ferrea by HPTLC and HPLC were reproductible. Abbreviations used: HPTLC: high performance thin layer chromatography, HPLC: high performance liquid chromatography, UV-Vis: spectrophotometry.


Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule.
Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining the functions of the proximal tubule epithelial layer-selective filtration and reabsorption. In this report, pseudo proximal tubule cells extracted from human-induced pluripotent stem cell-derived kidney organoids are combined and cultured with immortalized proximal tubule cells. It is shown that the cocultured tissue is an impervious epithelium that offers improved levels of certain transporters, extracellular matrix proteins collagen and laminin, and superior glucose transport and P-glycoprotein activity. mRNA expression levels higher than those obtained from each cell type were detected, suggesting an anomalous synergistic crosstalk between the two. Alongside, the improvements in morphological characteristics and performance of the immortalized proximal tubule tissue layer exposed, upon maturation, to human umbilical vein endothelial cells are thoroughly quantified and compared. Glucose and albumin reabsorption, as well as xenobiotic efflux rates through P-glycoprotein were all improved. The data presented abreast highlight the advantages of the cocultured epithelial layer and the non-iPSC-based bilayer. The in vitro models presented herein can be helpful in personalized nephrotoxicity studies.


Stiffness control of balance during dual task and prospective falls in older adults: the MOBILIZE Boston Study.
Outdoor fallers differ from indoor fallers substantially in demographics, lifestyle, health condition and physical function. Biomechanical predictors of outdoor falls have not been well characterized. Current validated measures of postural deficits, which describe only the overall postural behavior, are predictive of indoor falls but not outdoor falls. We hypothesized that a model-based description of postural muscle tone and reflexes, particularly during dual tasking, would predict outdoor falls. We tested whether postural stiffness and damping from an inverted pendulum model were predictive of future indoor and outdoor falls among older adults from the MOBILIZE Boston Study. The center of pressure data during standing were obtained from 717 participants aged 77.9±5.3 years. Participants stood barefoot with eyes open for 30s per trial, in two sets of five standing trials. One set included a serial subtractions task. Postural stiffness and damping values were determined from the postural sway data. After the postural measurements, falls were monitored prospectively using a monthly mail-in calendar over 6-36 months. Associations of postural measures with fall rates were determined using negative binomial regressions. After covariate adjustments, postural stiffness (p=0.02-0.05) and damping (p=0.007-0.1) were associated with lower outdoor falls risk, but not with indoor falls. Results were invariant by direction (anteroposterior versus mediolateral) or by condition (quiet standing versus dual task). Outdoor fall risk may be tied to postural control more so than indoor falls. Dual tasking is likely related to fall risk among older and sicker older adults, but not those relatively healthy.


Brain Magnetic Resonance Imaging and Angiography in Children with Sickle Cell Anaemia in Uganda in a Cross-Sectional Sample.
Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments. A sub-sample (n=81) was selected from a cross-sectional study of children attending SCA clinic, including 52 (64.2%) with and 29 (35.8%) without clinically detected abnormalities. Clinical evaluation included assessment for prior stroke, cognitive testing and cerebral arterial transcranial doppler (TCD) flow velocity. MRI-MRA scans were interpreted by at least two neuroradiologists. Mean age was 6.5±2.7 years, with 39 (48.1%) female. Mean haemoglobin was 7.3±0.9 g/dl. Overall, 13 (16.0%) were malnourished. Infarcts and/or stenoses were detected in 55 (67.9%) participants, with stenoses primarily in the anterior circulation. Infarcts were seen in those with normal 17/29 (58.6%) or abnormal 34/52 (65.4%) clinical testing (p=0.181). Neither abnormal MRI nor MRA was associated with age, sex, haemoglobin, or malnutrition. Abnormal MRA was highly associated with infarcts (p<0.0001). Participants with abnormal imaging had two-fold higher proportion of stroke on exam and/or impaired cognition. Stroke on exam was strongly associated with an imaging abnormality after adjusting for age, sex, malnutrition, and haemoglobin (OR 11.8, 95%CI 1.87-74.2). Over half of these SCA children had cerebrovascular infarcts and/or arterial stenoses. Cerebrovascular disease was frequently undetectable by clinical assessments. While rarely available in under-resourced settings, MRI-MRA brain imaging is an important tool for defining SCA cerebrovascular disease and for assessing impact of clinical intervention trials.


A novel combination of multiple primary carcinomas: urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma--report of a case and review of the literature.
The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90-100 packets per year). The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. It is important for the clinicians to keep in mind the possibility of a metachronous (successive) or a synchronous (simultaneous) malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous) is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.


The HLA and ABO antigens in pigment dispersion syndrome.
We found no statistically significant differences in phenotype frequencies of the 36 different HLA antigens or the ABO antigens when we compared 27 white patients with pigment dispersion syndrome (18 without glaucoma and nine with glaucoma) with 323 white controls. An increase was suggested in the incidence of B7 in patients without glaucoma, and of B13 among patients with glaucoma.


Expression and properties of the mitochondrial and cytosolic forms of aconitase in maize scutellum.
Aconitase (EC 188.8.131.52) catalyzes the reversible interconversion of citrate, cis-aconitate, and D-isocitrate. It operates in mitochondria and cytosol. We investigated the expression of two aconitase genes (Aco1 and Aco4) and activities of the mitochondrial and cytosolic forms in maize (Zea mays L.) scutellum during germination. Both forms were isolated and purified. The cytosolic form had a higher pH optimum (8.0), twice higher affinity to citrate (K(m) 9.5 mM), and slightly lower affinity to D,L-isocitrate (K(m) 1.7 mM) as compared to the mitochondrial form (optimum pH 7.5, K(m) with citrate 21 mM, and K(m) with isocitrate 1.5 mM). The highest activity of both forms of aconitase was observed on the 4th day of germination; then the activity and expression of the cytosolic form sharply decreased, while the mitochondrial form decreased more slowly. The mitochondrial aconitase was more strongly inhibited by H2O2 (half-inhibition at 35 μM) than the cytosolic form (60 μM). Aconitase activity was not detected in the glyoxysomal fraction beyond the cross-contamination level. It is suggested that the mitochondrial form operates in the tricarboxylic acid cycle, whereas the cytosolic form participates in the reactions of the glyoxylate cycle taking place outside the glyoxysome.


Human CD34(+) progenitor hematopoiesis in liquid culture for in vitro assessment of drug-induced myelotoxicity.
Utilization of validated CFU-GM assays for myelotoxicity screening is hampered by its labor-intensive and low-throughput nature. Herein, we transformed the defined CFU-GM assay conditions and IC90 endpoint into a higher throughput format. Human CD34(+) hematopoietic progenitors were cultured in a 96-well plate for 14 days with the same cytokine (rhGM-CSF) used in the CFU-GM assay. Expansion and differentiation toward myeloid lineages were manifested by characteristic changes in nuclear and cytoplasmic morphology and by temporal expression patterns of CD34, CD11b and CD13 markers. Inhibition of CD34(+) cell myelopoiesis by 12 anticancer drugs known to induce myelotoxicity in the clinic was quantifiable using either general cytotoxicity endpoints (cell growth area or total nucleus count) or lineage specific readouts (count of cells expressing CD11b and/or CD13). The IC50 and IC90 values derived from the concentration-response curves of 14-day drug exposure in CD34(+) cell culture were highly correlated with those from the international validation study of the CFU-GM assay, demonstrating capability to assess general cytotoxicity, cell proliferation and myelopoiesis simultaneously. These results suggest that this human CD34(+) hematopoietic progenitor cell assay can be used as a direct replacement for the validated, low throughput CFU-GM assay, and could expand application of in vitro myelotoxicity testing.


Transcranial magnetic stimulation treatment for epilepsy: can it also improve depression and vice versa?
Comorbidity with depression is an important determinant of the quality of life for patients with epilepsy. Antidepressant medications can effectively treat depression in epileptic patients, but drug-drug interactions and epileptogenic effects of these drugs pose therapeutic challenges. The mood-stabilizing effects of antiepileptic medications may not be sufficient to treat depression. Therefore, treatments that alleviate the burden of depression without increasing seizure risk or, better yet, with the possibility of improving seizure control are worth exploring. Neuroimaging techniques, such as functional magnetic resonance imaging, are providing novel insights into the pathophysiology of depression in epilepsy. For example, there appears to be prominent brain prefrontal hypoactivity, which may be sustained by the hyperactivity of the seizure focus. If so, neuromodulatory approaches that suppress epileptic focus hyperactivity and concurrently enhance prefrontal activity may be ideally suited. Indeed, vagus nerve stimulation has been shown to yield simultaneous antiseizure and mood effects. Another neuromodulatory technique, transcranial magnetic stimulation (TMS), can also modulate brain activity, but in a noninvasive, painless, and focal manner. Depending on the stimulation parameters, it is possible to enhance or reduce activity in the targeted brain region. Furthermore, TMS has been shown to be effective in treating depression, and preliminary data suggest that this treatment may also be effective for epilepsy treatment. This article reviews these data and explores further the question of whether depression and epilepsy can be simultaneously treated with TMS for optimal therapeutic impact.


Comparison of a conventional and an initial 2-month intensive drug regimen for treating pulmonary tuberculosis in Swaziland.
In an area where default from out-patient treatment for tuberculosis is very frequent and leads to 16% known failures on the 2SHT/16HT regimen, a 1-year follow-up study was carried out on 201 new sputum smear-positive patients who were hospitalised for the first 2 months of treatment. The first 103 patients were treated with 2SHT/10HT and the remaining 98 with 2SHRZ/10HT. In the first group 15 (17%) out of 89 traced patients were sputum-positive on a single smear after 1 year, compared with 1 (1%) out of 78 in the second group (P less than 0.001).


Adenosine diphosphate induced platelet aggregation and release reaction in heparinized platelet rich plasma and the influence of added citrate.
Platelets in heparinized platelet-rich plasma (PRP) from 54 volunteers were examined for their ability to aggregate and to release tritiated 5-hydroxy tryptamine (3H-5HT) in response to adenosine diphosphate (ADP). Release of 3H-5HT was considerable in 26 of the preparations. When release was high, lower concentrations of ADP were required to induce irreversible aggregation. Second phase aggregation reflected extensive release reaction. Citrate always augmented the release induced by ADP.


Prognostic value of the immunological phenomena and relationship with clinicopathological characteristics of the tumor--the expression of the early CD69+, CD71+ and the late CD25+, CD26+, HLA/DR+ activation markers on T CD4+ and CD8+ lymphocytes in squamous cell laryngeal carcinoma. Part II.
One of the most important challenges in contemporary oncology is to find objective biomarkers of tumor aggressiveness, which help to identify more invasive phenotypes of the carcinoma. The purpose of this study was to investigate the relationships between the early and the late activation markers expression on T CD4(+) and CD8(+) cells subpopulations and certain clinicopathological characteristics of the neoplastic infiltration in order to determine their role as biomarkers for tumor behavior in squamous cell laryngeal carcinoma. Analysis of the early (CD69(+), CD71(+)) and the late activation antigens (CD25(+) (high), CD26(+), HLA/DR(+)) expression on T CD4+ and CD8(+) lymphocytes by cytofluorymetry in 55 patients treated for squamous cell laryngeal carcinoma was performed. Clinicomorphological analysis on the basis of TNM criteria and tumor front grading, which included tumor-related features and adjacent stroma-related characteristics of the peripheral edge of infiltration was carried out. The relationships between the activation markers expression and parameters of tumor aggressiveness were investigated. Our work revealed statistically significant differences in the expression of the studied activation markers on T cells with regard to certain clinicomorphological features. The expressions of CD69(+) and CD71(+) antigens on T CD3(+)CD4(+) and CD3(+)CD8(+) cells as well as CD4(+)HLA/DR(+) markers were higher for pT3 and pT4 tumors, in comparison with pT2 carcinomas. Moreover, tumors with the smallest number of TFG points were characterized by significantly lower values of the average expression of CD3(+)CD69(+) and CD3(+)CD71(+) as well as CD4(+)HLA/DR(+) markers on T lymphocytes. In addition, more aggressive and deeply infiltrating laryngeal carcinomas were most often characterized by significantly higher values of the average expression of CD69(+) and CD71(+) antigens on CD8(+) as well as HLA/DR(+) markers on CD4(+). Our study confirmed the implication of the early and the late activation antigens expression on CD4(+) and CD8(+) T lymphocytes in clinicomorphological parameters of the tumor, especially TFG total score and depth of invasion, and their importance as indicators of the invasive phenotype of laryngeal carcinoma.


Magnetic resonance imaging for pancreatic ductal adenocarcinomas induced by N-nitrosobis (2-oxopropyl) amine in Syrian golden hamsters.
This study aimed to study magnetic resonance imaging (MRI) findings of pancreatic ductal adenocarcinomas (PDAs) induced by N-nitrosobis (2-oxopropyl) amine (BOP) in Syrian hamsters. A total of 101 female hamsters, 8 weeks old, were randomized into 3 groups. They were randomized into a BOP-treated group (n = 80; with weekly subcutaneous injections of BOP [10 mg/kg body weight] for 7 consecutive weeks), a saline-treated group (n = 16), and an untreated group (n = 5). Hamsters underwent abdominal MRI on 1.5-T MR scanners with a dedicated animal radiofrequency coil. Findings of the tumor from the MRI were compared those from histology. Pancreata in the saline-treated and in the untreated groups were normal. In the BOP-treated group, there were 23 and 31 BOP-induced PDAs on macroscopy and microscopy, respectively. Of the PDAs detected on macroscopy, 65.2% were depicted on MRI. As early as 13 and 19 weeks after the first injection of BOP, PDAs in hamsters were found on histology and MRI, respectively. Moreover, the tumor volume on MRI was correlated with the tumor weights excised (r = 0.96, P = 0.000, n = 15). N-nitrosobis (2-oxopropyl) amine successfully induced PDAs in hamsters. Magnetic resonance imaging has the ability to detect healthy pancreas and PDAs in hamsters and has the potential to monitor the development of PDAs.


Influence of trait anxiety on brain activity during the acquisition and extinction of aversive conditioning.
We examined how individual differences in trait anxiety (TA) influence the neural responses associated with the acquisition and extinction of anticipatory anxiety elicited through a context conditioning paradigm, with particular focus on the amygdala and the subgenual anterior cingulate cortex (sgACC). During two sessions of echo-planar functional magnetic resonance imaging (fMRI), 18 healthy volunteers completed a decision-making task with two randomly alternating 28-s to 32-s background screen colour blocks. One of the colours was associated with the presentation of an aversive noise (CTX+) and the other colour was 'safe' (CTX-). In the first session (Acquisition), 33% of CTX+ colour blocks were paired with noise and in the second session (Extinction) no noise was presented. The amygdala displayed an increased response to CTX+ compared to CTX- colour blocks during the Acquisition and Extinction sessions and the ACC displayed an increased response to CTX+ compared to CTX- colour blocks during Extinction only. In addition, a greater conditioned response (CTX+ minus CTX-) was observed in the ACC when comparing the Extinction and Acquisition sessions. Correlation analyses further showed that higher levels of TA were associated with a higher conditioned response in the amygdala during Extinction as well as a greater differential conditioned response (i.e. Extinction>Acquisition) in the ACC. Our results support the idea that individuals with high levels of anxiety-relevant traits and vulnerable to developing an anxiety disorder display a more resilient anxiety response during extinction that is characterized by hyper-responsivity in the amygdala.


Hb Warsaw (beta 42 Phe----Val): an unstable hemoglobin with decreased oxygen affinity. I. Hematologic and clinical expression.
Four members in two generations of a Polish-American family exhibited findings of congenital Heinz-body hemolytic anemia accompanied by cyanosis. Two of the affected family members have also developed severe pulmonary hypertension, with a fatal outcome in one of them. Blood from the affected individuals showed decreased oxygen affinity and contained elevated levels of methemoglobin. An unstable hemoglobin fraction underwent rapid precipitation following exposure of the red cell lysates to isopropyl alcohol or heat. This hemoglobin contained a newly identified abnormal beta chain with an amino acid substitution at the same position as that of Hb Hammersmith and Hb Bucuresti-Louisville.


South East Asia, Differing Socioeconomic Factors, Differing Access to Radiotherapy: The Philippines, a Microcosm.
The accessibility of radiotherapy in Southeast Asia, a region characterized by diversity in both economy and culture, differ widely among its member countries. In most countries, access is not universal and is generally limited by radiotherapy resources and the health-seeking behavior of patients. This in turn relates to the current health policy in place, the practice of radiation oncology, and cultural factors such as religion and family dynamics. Although it is clear that radiotherapy access parallel economic development, it is also affected by different social factors that work to facilitate or impede its improvement. These factors are herein described in relation to the Philippine situation, where there is wide economic disparity, multiple subcultures, and logistical impediments to improving radiotherapy access, reminiscent of the Southeast Asian region. In the face of increasing cancer burden, it becomes increasingly important to improve services and develop new and efficient approaches taking different cultural factors into consideration. Through regional and international cooperation, solutions to the common and complex problem of inequity in radiotherapy access may be developed.


[Bacteriotherapy of intestinal dysbacteriosis in patients with acute leukemia].
The results have been presented of correcting intestinal microflora in 127 patients with acute leukemia by preparations containing Bacillus bifidus and acidophilus: dried and milk bifidum-bacterin, biofructolact, acidophilic milk.


Experiences with the quality of telemedical care in an offshore setting - a qualitative study.
The evaluation and the improvement of the quality of telemedical care become increasingly important in times where this type of care is offered to a broad number of patients more and more. As telemedical care in an offshore setting has already been in use for decades, analyzing the extensive experience of offshore paramedics using telemedical care can help identify determinants of quality. Therefore, the aim of this study was to explore determinants of the quality of telemedical care using the experiences of experienced offshore paramedics. We conducted a qualitative analysis of 22 semi-structured interviews with experienced offshore paramedics. The results were categorized in a hierarchical category system using content analysis as described by Mayring. All 22 participants were males, having a mean of 3.9 years of experience working with telemedicine support offshore. Generally, participants stated that for them telemedical interaction did not differ much from personal interaction. However, the offshore paramedics personality and way to communicate were mentioned to impact the quality of telemedical care as it influenced the way cases were presented. Furthermore, interviewees described it to be impossible to use telemedicine in cases of an emergency as it was too time-consuming, technically too complex, and lead to cognitive overload as other tasks with higher priority needed their attention. Three determinants of a successful consultation were mentioned: low levels of complexity in the reason for consultation, telemedical guidance training for the teleconsultant physician and for the delegatee. Appropriate indications for telemedical consultation, communication training of consultation partners, and the impact of personality need to be addressed to enhance the quality of future telemedical care.


Selectivity in L1 Attrition: Differential Object Marking in Spanish Near-Native Speakers of English.
Previous research has shown L1 attrition to be restricted to structures at the interfaces between syntax and pragmatics, but not to occur with syntactic properties that do not involve such interfaces ('Interface Hypothesis', Sorace and Filiaci in Anaphora resolution in near-native speakers of Italian. Second Lang Res 22: 339-368, 2006). The present study tested possible L1 attrition effects on a syntax-semantics interface structure [Differential Object Marking (DOM) using the Spanish personal preposition] as well as the effects of recent L1 re-exposure on the potential attrition of these structures, using offline and eye-tracking measures. Participants included a group of native Spanish speakers experiencing attrition ('attriters'), a second group of attriters exposed exclusively to Spanish before they were tested, and a control group of Spanish monolinguals. The eye-tracking results showed very early sensitivity to DOM violations, which was of an equal magnitude across all groups. The off-line results also showed an equal sensitivity across groups. These results reveal that structures involving 'internal' interfaces like the DOM do not undergo attrition either at the processing or representational level.


Self-reactive T cell clones in a restricted population of interleukin-2 receptor beta+ cells expressing intermediate levels of the T cell receptor in the liver and other immune organs.
T cells expressing high levels of the T cell receptor (TCRhigh) differentiate in the major intrathymic pathway and then distribute to the peripheral immune organs, whereas T cells expressing intermediate levels of the TCR (TCRint) differentiate in both extrathymic pathways and an alternative intrathymic pathway and localize in unique sites, including the liver and thymic medulla. Since TCRint cells constitutively express interleukin-2 receptor beta-chain (IL-2R beta), two-color staining for CD3 (or TCR) and IL-2R beta clearly distinguished IL-2R beta+ CD3int (or TCRint) cells from IL-2R beta-, CD3high cells. CD3int cells may be considered to be primordial T cells based on their phenotype, morphology and other functional properties. In this study, using anti-V beta mAb in conjunction with the endogenous superantigen Mls, the distribution of self-reactive clones among T cells generated in all of the above pathways was investigated in mice. Self-reactive T cell clones were confined to IL-2R beta+, CD3int cells, in all of the organs tested. A significant proportion of self-reactive clones was never identified among CD3high cells in the thymus and peripheral immune organs in either young (8 week old) or old (50 week old) mice. Possibly reflecting their self-reactivity, CD3int cells, but neither NK cells nor CD3high cells had a potent cytotoxic effect against a syngeneic hepatoma in the presence of anti-CD3 mAb. These results raise the possibility that CD3int cells seen in the liver and thymus might belong to a similar primordial lineage of T cells, and that self-reactive clones are not generated through the major intrathymic pathway, but only through extrathymic pathways and an alternative intrathymic pathway.


DISTANCE DATA REVISITED.
Abstract- Objections to my earlier demonstration, that the branch lengths of trees fitted to distance matrices have no physical interpretation, are shown to be ill-founded. In particular the contention of Felsenstein, that fitted lengths estimate expectations of amounts of change, is shown to lead to a paradox. A method is introduced for constructing multiple trees of optimal or near-optimal fit to distance data, and this is found to give better performance than previous methods. Most published trees based on distances have been poorly chosen. Consensus trees of several trees with near-optimal fit are found to be quite poorly resolved, and it appears that molecular distances seldom provide much useful information on phylogenetic relationships.


Marine Cellulases and their Biotechnological Significance from Industrial Perspectives.
Marine microorganisms represent virtually unlimited sources of novel biological compounds and can survive extreme conditions. Cellulases, a group of enzymes that are able to degrade cellulosic materials, are in high demand in various industrial and biotechnological applications, such as in the medical and pharmaceutical industries, food, fuel, agriculture, and single-cell protein, and as probiotics in aquaculture. The cellulosic biopolymer is a renewable resource and is a linearly arranged polysaccharide of glucose, with repeating units of disaccharide connected via β-1,4-glycosidic bonds, which are broken down by cellulase. A great deal of biodiversity resides in the ocean, and marine systems produce a wide range of distinct, new bioactive compounds that remain available but dormant for many years. The marine environment is filled with biomass from known and unknown vertebrates and invertebrate microorganisms, with much potential for use in medicine and biotechnology. Hence, complex polysaccharides derived from marine sources are a rich resource of microorganisms equipped with enzymes for polysaccharides degradation. Marine cellulases' extracts from the isolates are tested for their functional role in degrading seaweed and modifying wastes to low molecular fragments. They purify and renew environments by eliminating possible feedstocks of pollution. This review aims to examine the various types of marine cellulase producers and assess the ability of these microorganisms to produce these enzymes and their subsequent biotechnological applications.


A gas-to-particle conversion mechanism helps to explain atmospheric particle formation through clustering of iodine oxides.
Emitted from the oceans, iodine-bearing molecules are ubiquitous in the atmosphere and a source of new atmospheric aerosol particles of potentially global significance. However, its inclusion in atmospheric models is hindered by a lack of understanding of the first steps of the photochemical gas-to-particle conversion mechanism. Our laboratory results show that under a high humidity and low HOx regime, the recently proposed nucleating molecule (iodic acid, HOIO2) does not form rapidly enough, and gas-to-particle conversion proceeds by clustering of iodine oxides (IxOy), albeit at slower rates than under dryer conditions. Moreover, we show experimentally that gas-phase HOIO2 is not necessary for the formation of HOIO2-containing particles. These insights help to explain new particle formation in the relatively dry polar regions and, more generally, provide for the first time a thermochemically feasible molecular mechanism from ocean iodine emissions to atmospheric particles that is currently missing in model calculations of aerosol radiative forcing.


Genetic interstitial lung disease.
The interstitial lung diseases (ILDs), or diffuse parenchymal lung diseases, are a heterogeneous collection of more than 100 different pulmonary disorders that affect the tissue and spaces surrounding the alveoli. Patients affected by ILD usually present with shortness of breath or cough; for many, there is evidence of pulmonary restriction, decreased diffusion capacity, and radiographic appearance of alveolar and/or reticulonodular infiltrates. This article reviews the inherited ILDs, with a focus on the diseases that may be seen by pulmonologists caring for adult patients. The authors conclude by briefly discussing the utility of genetic testing in this population.


Quantitative assessment of common genetic variations in HLA-DP with hepatitis B virus infection, clearance and hepatocellular carcinoma development.
Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Recently, genome-wide association studies have identified human leukocyte antigen (HLA)-DP polymorphisms (rs3077 and rs9277535) as a new chronic HBV infection susceptibility locus. Since then, the relationship between HLA-DP polymorphisms and various outcomes of HBV infection has been reported. However, the results have been inconclusive. To derive a more precise estimation of the relationship between HLA-DP polymorphisms and various outcomes of HBV infection, a meta-analysis of 62,050 subjects from 29 case-control studies was performed. We found that rs3077 and rs9277535 in HLA-DP significantly decreased HBV infection risks and increased HBV clearance possibility in a dose-dependent manner. In the subgroup analysis by ethnicity, study design and sample size, significant associations were found for these polymorphisms in almost all comparisons. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and HBV infection outcomes. However, no significant results were observed in HCC development. Our results further confirm that genetic variants in the HLA-DP locus are strongly associated with reduced HBV infection and increased the likelihood of spontaneous viral clearance.


Recollections of Professor Henry Barcroft, F.R.S.
Professor Henry Barcroft, MD, FRS, Emeritus Professor of Physiology in St. Thomas' Hospital Medical School in London died on 11 January 1998, aged 93. He was born in Cambridge on 18 October 1904 where his father, Joseph Barcroft, a famous physiologist, worked with Foster and Langley and subsequently was appointed to the Chair of Physiology. Henry Barcroft followed in his father's footsteps. During his career as Professor of Physiology firstly at The Queen's University of Belfast and subsequently at St. Thomas's Hospital London, he made significant studies on the nervous and humoral control of human blood vessels. His success as a research scientist stemmed partly from his ability to simplify complex phenomena in a way that permitted them to be broken into component parts and tested and partly from his technical ingenuity that permitted simple, inexpensive measurements of difficult physiological variables. Perhaps the most important factor, however, was his ability to bring out and stimulate aptitudes and enthusiasms in others. Completely unselfish himself, he gave individuals every opportunity to develop their talents, and so make themselves known to a wide circle of interested medical scientists. In many ways, his life was a guidebook for young scientists on how to make the most of their opportunities.


Current strategies for sustaining drug release from electrospun nanofibers.
Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning.


Exome and genome sequencing for rare genetic disease diagnosis: A scoping review and critical appraisal of clinical guidance documents produced by genetics professional organizations.
Exome and genome sequencing have rapidly transitioned from research methods to widely used clinical tests for diagnosing rare genetic diseases. We sought to synthesize the topics covered and appraise the development processes of clinical guidance documents generated by genetics professional organizations. We conducted a scoping review of guidance documents published since 2010, systematically identified in peer-reviewed and gray literature, using established methods and reporting guidelines. We coded verbatim recommendations by topic using content analysis and critically appraised documents using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. We identified 30 guidance documents produced by 8 organizations (2012-2022), yielding 611 recommendations covering 21 topics. The most common topic related to findings beyond the primary testing indication. Mean AGREE II scores were low across all 6 quality domains; scores for items related to rigor of development were among the lowest. More recently published documents generally received higher scores. Guidance documents included a broad range of recommendations but were of low quality, particularly in their rigor of development. Developers should consider using tools such as AGREE II and basing recommendations on living knowledge syntheses to improve guidance development in this evolving space.


Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options.
Drug-induced liver injury (DILI) is a rare but potentially life threatening adverse drug reaction. DILI may mimic any morphologic characteristic of acute or chronic liver disease, and the histopathologic features of DILI may be indistinguishable from those of other causes of liver injury, such as acute viral hepatitis. In this review article, we provide an update on causative agents, clinical features, pathogenesis, diagnosis modalities, and outcomes of DILI. In addition, we review results of recently reported genetic studies and updates on pharmacological and invasive treatments.


A technical infrastructure to conduct randomized database studies facilitated by a general practice research database.
General practice research databases are increasingly used to study intended and unintended effects of treatments. However, confounding by indication remains a major problem. The randomized database study methodology has been proposed as a method to combine the strengths of observational database (generalizability) and the strength of the randomized clinical trial (RCT) design (randomization). We developed an infrastructure that enables the execution of randomized database studies with treatment randomization facilitated by a general practice research database. The requirements posed by the methodology of randomized database studies were facilitated by software components. Our assessment showed that it is technically possible to conduct randomized trials in general practice according to the randomized database design. The infrastructure facilitated the conduct of randomized database studies in general practice but some practical difficulties and methodological issues remain. The technical infrastructure seems to be both promising and potentially feasible to facilitate future randomized database studies, although the methodology needs to be evaluated in more detail.


Early medial reconstruction combined with severely injured medial collateral ligaments can decrease residual medial laxity in anterior cruciate ligament reconstruction.
This study aimed to describe an anatomic medial knee reconstruction technique for combined anterior cruciate ligament (ACL) and grade III medial collateral ligament (MCL) injuries and to assess knee function and stability restoration in patients who underwent primary MCL reconstruction compared with primary repair. A total of 105 patients who had undergone anatomic ACL reconstruction between 2008 and 2017 were enrolled in this retrospective study and divided into two groups according to concomitant MCL ruptures. Group A included patients with isolated ACL ruptures without MCL injuries. Group B included patients with both ACL and MCL injuries, and it was subdivided into three groups according to the severity of the MCL injury and treatment modality: B-1, grade I or II MCL injury treated conservatively; B-2: grade III MCL injury treated by primary MCL repair; and B-3: grade III MCL injury treated by primary reconstruction. Knee stability was measured via Telos valgus radiography at 6-month and 2-year postoperative. The Lysholm score, Tegner activity level, Likert scales (satisfaction), and return to previous sports were evaluated at 2-year postoperative. At 6-month postoperative, there was no significant difference in medial laxity between the B-2 and B-3 groups. However, at 2-year postoperative, medial laxity were significantly higher both at 30° of flexion (5.2° versus 2.2°, p = 0.020) and at full extension (3.4° versus 1.1°, p < 0.001) in patients in B-2 group compared to those in B-3 group. There were no statistically significant differences between the two groups with respect to Lysholm scores, Tegner activity levels, Likert scales (satisfaction), and returning to previous sports at the 2-year follow-up. Primary medial reconstruction combined with severely injured MCL in ACL reconstruction may decrease residual medial laxity more than primary repair. Retrospective observational study, IV.


Combination of midazolam and flumazenil in upper gastrointestinal endoscopy, a doubleblind randomized study.
We evaluated the clinical usefulness of flumazenil (formerly Ro15-1788), a benzodiazepine antagonist, in combination with midazolam in upper gastrointestinal endoscopy. Thirty outpatients were randomized into two groups: those receiving flumazenil and those receiving placebo after endoscopy. For sedation, only midazolam was used. Performances pre-sedation and post-sedation (at 30 and 60 min) were analyzed using the Trieger test, Number Connection test, and Digit Symbol test. Patients receiving flumazenil were fully alert and able to ambulate 5 min after injection with this medication. Performances at 30 min in the Trieger, Number Connection, and Digit Symbol tests were significantly better in the group receiving flumazenil, p less than 0.005, p less than 0.025, and p less than 0.01, respectively. No phlebitis, nausea, vomiting, or anxiety were noted. No resedation events were documented. We conclude that flumazenil can dramatically shorten the recovery period following sedation with midazolam in upper gastrointestinal endoscopy, and its use is not associated with major side effects.


Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol.
In animal studies, hypercholesterolemia induced by cholesterol feeding results in the plasma cholesterol being transported by lipoproteins of lower densities. Little information is available for humans. To determine the specific lipoprotein responses to dietary cholesterol challenge in humans, four volunteer subjects ingested a liquid formula diet containing 5000 mg of egg yolk cholesterol per day for 30 days and the changes in their lipoprotein fractions were examined. The high dietary cholesterol (above the range of normal diet) was associated with marked increases in apolipoprotein B and low density lipoprotein (LDL) cholesterol levels. An elevated cholesterol : triglyceride ratio in the LDL fraction indicated that the diet altered both LDL level and composition. High density lipoprotein cholesterol and apolipoprotein AI increased slightly. Very low and intermediate density lipoprotein cholesterol and apolipoprotein E levels did not increase during the diet. Thus, high dietary cholesterol was associated with major changes in LDL level and composition, but only minor changes in the other lipoprotein fractions and suggested only minor accumulation of remnant particles.


Fine-needle aspiration biopsy and the diagnosis of thyroid cancer.
Conventional criteria for the evaluation of thyroid nodules are inaccurate in identifying the small proportion of malignant neoplasms. The diagnostic accuracy of fine-needle aspiration biopsy (FNAB) for cytology was therefore assessed in 562 patients with nodular thyroid disease, 373 of whom (66.4 per cent) had histological confirmation of the cytological diagnosis. Sixty-one aspiration biopsies were positive for malignancy, and the diagnosis was confirmed histologically in 59 of these (96.7 per cent). Thus, there were two false positive cytology results among 310 patients with proven benign disease (0.6 per cent). Four of sixty-three patients with proven carcinoma had a benign cytological diagnosis, a false negative rate of 6.3 per cent. In 57 of the 59 malignancies (96.6 per cent) correctly diagnosed by FNAB the histological type of tumour was successfully identified. Overall 367 of 373 patients received correct cytological discrimination between benign and malignant nodules, an overall accuracy of 98.4 per cent for FNAB. The sensitivity of the test was 93.7 per cent and the specificity 99.4 per cent. Besides being safe, cost-effective and reliable, FNAB directs the appropriate selection of patients for surgery and enables the correct operation to be performed for each type of tumour.


Nutritional genomics, polyphenols, diets, and their impact on dietetics.
Nutritional genomics offers a way to optimize human health and the quality of life. It is an attractive endeavor, but one with substantial challenges. It encompasses almost all known aspects of science, ranging from the genomes of humans, plants, and microorganisms, to the highest levels of food science, analytical science, computing, and statistics of large systems, as well as human behavior. This paper describes the underlying biochemistry that is targeted by the principal issues in nutritional genomics, which entails genomics, transcriptomics, proteomics, and metabolomics. A major feature relevant to nutritional genomics is the single nucleotide polymorphisms in genes that interact with nutrients and other bioactive food components. These genetic changes may lead to alterations in absorption, metabolism, and functional responses to bioactive nutritional factors. Bioactive food components may also regulate gene expression at the transcriptome, protein abundance, and/or protein turnover levels. Even if all of these variables are known, additional variables to be considered include the nutritional variability of the food (unprocessed and processed), the amount that is actually eaten, and the eating-related behaviors of those consuming the food. These challenges are explored within the context of soy intake. Finally, the importance of international cooperation in nutritional genomics research is presented.


Importance of subsegmental pulmonary embolism.
In this issue of Blood, den Exter et al highlight the importance of subsegmental pulmonary emboli.


Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.
The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.


Spike activity and histofluorescence correlated in the giant dopamine neurone of Planorbis corneus.
The relationship between catecholamine fluorescence and electrical activity of the nerve cell has been investigated in the giant dopamine neuron (GDN) of the left pedal ganglion of the European water snail, Planorbis corneus. Electrical recordings were performed in vitro with intracellular microelectrodes on 35 GDN. The ganglion was frozen to -195 degrees C with the electrode in situ and processed for histochemical microfluorimetry. The intensity of catecholamine fluorescence was measured over different places (42/cell) throughout the cytoplasm of the GDN. In order to investigate the temporal relation between histochemical and electrophysiological parameters, the activity of 21 GDN was changed by administration of nicotine to the bathing solution (10(-5)--10(-7) M). This treatment was followed by depolarization in most of the GDN, with increased firing in two thirds and decreased activity in one third of the spontaneously active cells, whereas hyperpolarization was seen in 4 GDN, accompanied by a decrease in firing. Acetylcholine (10(-5) M) tested on one GDN caused depolarization and increased firing. A signigicant positive correlation was found between the fluorescence intensity of individual GDN and the firing rate of these cells as observed during the last 60 sec or the last 10 sec before freezing. The correlation coefficient dropped markedly when the first rates of the 2nd, 3rd, or 4th and 5th min before freezing were correlated with cellular fluorescence intensity. Intensity was not correlated with the resting membrane potential recorded at the time of freezing. The intensity response to activation was not uniform throughout the cytoplasm of GDN. Neurons with increased mean fluorescence intensity regularly showed small clusters and cristae of intensely fluorescent material surrounded by less fluorescent parts of the cytoplasm. This morphological observation of increased intensity differences between cytoplasmic structures was confirmed by the statistics of the intensity values determined in individual cells. The present observations demonstrate the existence of a relation between cell firing and neuronal dopamine fluorescence at the level of the individual nerve cell. The activity immediately preceding the time of freezing of the cell appears to be most important. Certain components of the cytoplasm appear to react preferentially; their subcellular nature remains to be elucidated. The link between electrical activity and cellular dopamine fluorescene was found to be basically the same in the giatn invertebrate neuron and in the dopamine nerve cells of rat substantia nigra.


Exploring properties of potassium 6-X-2-isonicotinoyltrifluoroborate (X=H, F, Cl, Br) salts and their anions by using ab initio calculations.
The structural, electronic, and topological properties of a series of four members of potassium 6-X-2-isonicotinoyltrifluoroborate (X=H, F, Cl, Br) salts have been explored by using ab initio calculations with the hybrid B3LYP/6-311++G** method. According to the potential energy surface only the properties for the most stable conformer of each member of the series and their anions were analyzed in function of electronegativity and atomic radius of X. The results show that when X=H, the salt and its anion have symmetry CS while the symmetry change to C1 for the halogenated F, Cl, and Br derivatives and their anions. Both, electronegativity and atomic radius properties show higher effects on V than on μ. Similar behaviors are observed when the Mulliken charges on N and X atoms are analyzed vs electronegativites, and atomic radius of X while an important decreasing on NPA charges of X is observed when increase its electronegativity. The strong influence of electronegativity and atomic radius of X are evidenced in the low bond order value observed in the C1 atom of F salt. The strong energetic π*C2-C3 → π*C4-C5 transition observed only for the F salt confer to it a high stability. The frontier orbitals have revealed that the 6-H-IFTB salt is the less reactive species while the higher reactivity is predicted for the Br salt. Evidently, the smaller electronegativity and higher atomic radius of Br justify the high reactivity predicted for its salt. Graphical abstractExploring properties of potasium 6-X-2-isonicotinoyltrifluoroborate (X= H, F, Cl, Br).


Collagen receptors mediate early events in the attachment of epithelial (MDCK) cells.
Madin-Darby canine kidney (MDCK) cells kept in suspension culture for 12-15 hr displayed high-affinity binding sites for 125I-lathyritic (soluble) collagen (120,000/cell, KD = 30 nM) and preferred collagens types I and IV over laminin or fibronectin as substrates during the first hour of attachment. On the other hand, after 4 hr, attachment to all four substrates was equally efficient. Upon challenge with a collagen substrate, the high-affinity sites were rapidly recruited on it (T1/2 = 6 min). Their occupancy by soluble collagen triggered the exocytosis of a second large population of low-affinity collagen binding sites that included laminin and seems to be involved in a second cell-attachment mechanism. These results are compatible with a two-step model of MDCK cell attachment to the substrate: first, via high-affinity collagen binding sites, and second, via laminin of cellular origin.


The beta 2-microglobulin locus of rainbow trout (Oncorhynchus mykiss) contains three polymorphic genes.
Beta2-microglobulin (beta2m) associates with MHC and related class I H chains to form cell surface glycoproteins that mediate a variety of functions in defense. In humans, monomorphism of a single beta2m gene contrasts with the diversity and polymorphism of the class I H chain genes, and a similar picture was seen in almost all other species examined. In this regard, rainbow trout (Oncorhynchus mykiss) appeared unusual: trout beta2m genes gave a complicated and polymorphic pattern in Southern blots, and a minimum of 10 different mRNA encoding two distinct types of beta2m were expressed by a single fish. Characterization of genomic clones from the same fish now shows that the rainbow trout beta2m locus consists of two expressed genes and one partial gene that are closely linked. Four copies of the locus were identified and allelic variants of each gene defined, largely through comparison of the noncoding regions. A dramatic variation in the lengths of introns is caused by variable repetitive elements and accounts for the complex pattern seen in Southern blots. By comparison to noncoding sequences, the coding regions are conserved but the three loci differ within a cluster of codons that encode residues of beta2m that do not interact with class I H chains. Additional diversity in the trout beta2m genes appears to be due to somatic mutation that might be facilitated by the abundance of repetitive DNA elements within the 12 beta2m genes of an individual rainbow trout.


Amino acid sequence of beta-galactoside-binding bovine heart lectin. Member of a novel class of vertebrate proteins.
A variety of animal tissues contain beta-galactoside-binding lectins with molecular masses in the range 13-17 kDa. There is evidence that these lectins may constitute a new protein family although their function in vivo is not yet clear. In this work the major part of the amino acid sequence of the 13 kDa lectin from bovine heart muscle has been determined. Comparison of this sequence with the cDNA-deduced sequence published for the chick embryo skin lectin showed 58% homology. Comparison of the bovine lectin sequence with partial sequences from two cDNA clones from a human hepatoma library and partial amino acid sequences of human lung lectin showed 70, 40 and 85% homology, respectively. The sequences of these vertebrate lectins are thus clearly related, supporting earlier results of immunological cross-reactivity within this group of proteins. Computer searching of protein sequence databases did not detect significant homologies between the bovine lectin sequence and other known proteins.


[Determination of fitness components of flies bearing the recessive lethal l(2)M167(DTS) mutation with dominant heat sensitivity in artificial Drosophila melanogaster populations].
Elimination of the heat-sensitive l(2)M167(DTS) mutation from artificial Drosophila melanogaster populations at constant temperature 25 degrees C and various frequencies of the mutation in the parental generation was studied. Components of fitness of the l(2)M167(DTS) mutation were estimated in the artificial populations by means of the recurrent model of the dependence of the frequency of this mutation in a given generation on its frequency in the previous generation. The model was solved by a numerical method with limitations on the values of some fitness components obtained in test experiments. According to the limitations and frequencies of the l(2)M167(DTS) mutation, the leading role and limits of the variation in egg-to-adult viability and female fertility were determined. The previously suggested effect of the positive selection for viability of individuals heterozygous for l(2)M167(DTS) was confirmed.


Exposure to low temperatures suppresses the production of B-cell activating factor via TLR3 in BEAS-2B cells.
Acute viral respiratory tract infections (RTIs) are commonly associated with cold weather; however, the mechanism behind this is still unclear. Secretory IgA (sIgA) mainly contributes to the immune response against pathogenic microorganisms in the respiratory tract. Certain pathogen-associated molecular patterns (PAMPs) induce the expression of B-cell activating factor (BAFF) in epithelial cells, macrophages, and dendritic cells. BAFF transforms B cells into plasma cells, which leads to the mass production of immunoglobulins, including IgA, on the mucosal epithelium. However, no studies have described the relationship between cold exposure and BAFF and/or sIgA in RTI. The aim of our study was to determine this relationship in vitro by investigating the effect of low temperature on BAFF production by BEAS-2B cells after the addition of toll-like receptor (TLR) ligands. We showed stimulation of polyinosinic:polycytidylic acid (poly I:C), which led BEAS-2B to produce interferon (IFN)-β. IFN-β itself induced BEAS-2B cells to produce BAFF. Janus kinase inhibitor I decreased the amount of BAFF produced in BEAS-2B cells upon stimulation with IFN-β and poly I:C. Significantly less BAFF was produced post-poly I:C stimulation in low-temperature conditions than in normal-temperature conditions (mean ± SD: 41.2 ± 23.3 [33 °C] vs. 138.3 ± 7.1 pg/mL [37 °C], P = 0.05). However, the low-temperature condition itself was not cytotoxic. The stimulation of poly I:C produced BAFF from BEAS2B cells via IFN-β production and the JAK/signal transducer and activator of transcription pathway played an important role in BAFF production in BEAS-2B cells. Cold exposure reduced BAFF production by BEAS2B cells after stimulation with the TLR3 ligand. Cold exposure may, therefore, suppress the production of BAFF, resulting in the inhibition of IgA secretion in the bronchial epithelium, which explains the increased frequency of RTIs in cold weather.


Ellisras Longitudinal Study 2017: patterns of physical activity in an urban and rural setting among black South African adults (ELS 23).
Understanding patterns of physical activity among adults can lead to targeted approaches to improve activity levels in the African population. This study aimed to determine whether age, gender, location and employment status could predict physical activity among rural and urban South African adults, and to determine the participants' risk of developing cardiovascular disease (CVD). A cross-sectional design was conducted on 319 participants of mean age 57 ± 10.43 years. Participants were sampled using a stratified random-sampling procedure from an urban township in Langa, Western Cape Province, and a rural township in Mt Frere, Eastern Cape Province, South Africa. A researcher-generated questionnaire was used to collect sociodemographic and physical activity data. Linear regression analysis was used to test predictive relationships. Gender and geographical location were significant predictors (p = 0.001) of physical activity. Rural participants engaged more in physical activity (91.5%) than urban participants (84.2%) and were more likely to meet the physical activity recommendations to promote cardiovascular fitness (p = 0.000). The most frequent physical activities in rural participants were walking (15.4%), household chores (18.8%) and household chores + gardening (15.4%). The most frequent physical activities in urban participants were household chores (34.2%), and household chores + walking (33.7%). In terms of duration of physical activity, rural participants spent longer periods engaging in activities lasting up to two hours (21.4%), compared to 5.9% in urban participants (p = 0.000). Gender and geographical location were significant predictors of physical activity among black South African adults. Overall, rural adults engaged in more physical activity than urban-dwelling adults. Males also engaged in more physical activity and at a higher intensity than females. Most rural participants met the American College of Sports Medicine recommendations for cardiovascular fitness and therefore were at minimal risk for developing CVD compared to their urban counterparts.


Significance of chondroitin sulfate isomers in the synovial fluid of osteoarthritis patients.
To test whether chondroitin sulfate (CS) isomers in synovial fluid are related to the radiographic severity of osteoarthritis (OA) and the age and sex, we investigated the concentrations of chondroitin 6-sulfate (C6S) and chondroitin 4-sulfate (C4S) in patients with OA of the knee joint and age-matched healthy controls. Synovial fluid was obtained from 133 patients with OA of the knee and 27 volunteers (controls). Twenty-seven patients were radiographically classified as grade 1, 59 as grade 2, 34 as grade 3, and 13 as grade 4 according to a modified version of the Kellgren and Lawrence scale. Compared with findings in the controls, values for the concentrations of C6S and C4S, and the C6 : C4S ratio, were significantly higher in the grade 1 patients, whereas in grade 3 and 4 patients, the C6S concentration and the C6 : C4S ratio were lower. There was an obvious sex difference, and all values for the women were significantly lower than those for the men in both the control and the patient groups. In the control group, multiple regression analysis showed a moderate inverse correlation between age and all three of the above biochemical variables, and sex was moderately associated with the C6S concentration and the C6S : C4S ratio. In the patient group, age and sex showed a poor correlation with any of the three variables. However, the radiographic severity of OA showed a relatively strong inverse correlation with the C6S concentration and the C6S : C4S ratio, and a weak inverse correlation with the C4S concentration.


[Determination of the concentrations of separate species of microorganisms in mixtures by the light scattering spectra of the suspensions].
A possibility of number determination of microorganisms in cultures mixture according to the spectra light transmission is shown.


Unrecognized fine-scale recombination can mimic the effects of adaptive radiation.
Gene sequences can undergo accelerated nucleotide changes and rapid diversification. The rapid sequence changes can then potentially lead to phylogenetic incongruence. Recently, Bodilis et al. (2011) observed artificial phylogenetic incongruence using the Pseudomonas surface protein gene oprF, and hypothesized that it was the result of a long-branch attraction artifact ultimately caused by adaptive radiation. In this study, an alternative hypothesis, namely fine-scale recombination, was tested on the same dataset. The results reveal that regions in oprF are of different evolutionary origins, and the mosaic gene structure resulted in confounding phylogenetic signals. These findings demonstrate that unrecognized fine-scale recombination can confound the phylogenetic interpretation and emphasize the limitation of using whole genes as the unit of phylogenetic analysis.


Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha.
Human urokinase-type plasminogen activator (uPA) is poorly secreted by yeast cells. Here, we have selected Hansenula polymorpha mutants with increased productivity of active extracellular uPA. Several of the obtained mutants also demonstrated a defect of sorting of carboxypeptidase Y to the vacuole and the mutant loci have been identified in six of them. All these mutations damaged genes involved in protein traffic between the Golgi apparatus and the vacuole, namely PEP3, VPS8, VPS10, VPS17, and VPS35. We have shown that inactivation of the VPS10 gene encoding the vacuolar protein sorting receptor does not increase uPA secretion but stimulates its proteolytic processing.


Cardiorespiratory functions in the fetal llama.
Factors which allow the adaptation of adult llamas to oxygen limitation include principally: low P50, small elliptical red cells with high hemoglobin concentration, high muscle myoglobin concentration, high capillary density and a more efficient O2 extraction at tissue levels. The fetal llama is known to have blood with a low P50 but it is not known whether it has further cardiorespiratory adaptations which could allow it to cope with a low oxygen milieu. To investigate this, we have measured fetal blood flow and blood oxygen content in 8 fetal llamas and compared the findings to similar measurements in 10 low altitude bred fetal sheep, during the last third of gestation. The llamas were born and raised at 4500 m. They were brought to Santiago (586 m) and were studied one week later. The results show that there was higher hemoglobin concentration and higher oxygen capacity in blood from the fetal llama compared to the fetal sheep. Fetal llama combined ventricular output and umbilical blood flow were less than one fourth of those found in fetal sheep. Regional blood flows and oxygen delivery to fetal tissues were in most cases less than half those found in the fetal sheep. Calculated vascular resistances in the fetal llama in almost all vascular beds are higher than those in fetal sheep. These studies suggest that basal fetal llama oxygen uptake is maintained due to an increased oxygen extraction by fetal llama tissues. This increased oxygen extraction may be the result of a high capillary density.(ABSTRACT TRUNCATED AT 250 WORDS)


Identifying the determinants of patient satisfaction in the context of antenatal care in Kenya, Tanzania, and Malawi using service provision assessment data.
Antenatal care (ANC) is a service that can reduce the incidence of maternal and neonatal deaths when provided by skilled healthcare workers. Patient satisfaction is an important health system responsiveness goal which has been shown to influence adherence to healthcare interventions. This study aims to assess the determinants of pregnant women's satisfaction with ANC across Kenya, Tanzania, and Malawi using nationally representative Service Provision Assessment data. Patient satisfaction was conceptualised mainly based on Donabedian's theory of healthcare quality with patient characteristics, structure, and process as the major determinants. Bivariate and multivariate analyses were conducted to identify the potential determinants. Findings show that satisfaction was negatively associated with women's age (AOR: 0.95; 95% CI: 0.92-0.99) and having a secondary (AOR: 0.39; 95% CI: 0.17-0.87) or tertiary education (AOR: 0.41; 95% CI: 0.17-0.99) in Kenya. Women on their first pregnancy were more likely to report satisfaction in Tanzania (AOR: 1.62; 95% CI: 1.00-2.62) while women were less likely to report being satisfied in their second trimester in Malawi (AOR: 0.31; 95% CI: 0.09-0.97). The important structural and process factors for patient satisfaction included: private versus public run facilities in Kenya (AOR: 2.05; 95% CI: 1.22-3.43) and Malawi (AOR: 1.85; 95% CI: 0.99-3.43); level of provider training, that is, specialist versus enrolled nurse in Tanzania (AOR: 0.35; 95% CI: 0.13-0.93) or clinical technician in Malawi (AOR: 0.08; 95% CI: 0.01-0.36); and shorter waiting times across all countries. Findings highlight the importance of professional proficiency and efficient service delivery in determining pregnant women's satisfaction with ANC. Future studies should incorporate both patient characteristics and institutional factors at health facilities into their conceptualisation of patient satisfaction.


Open-label trial of therapeutic immunization with oral V-5 Immunitor (V5) vaccine in patients with chronic hepatitis C.
We evaluated whether V-5 Immunitor (V5)--tableted therapeutic bivalent vaccine comprising heat-inactivated HCV antigens from pooled blood of HBV- and HCV-infected donors - may produce clinical benefit through induction of oral tolerance and reduction of immune-mediated liver injury. Once daily dose of V5 was administered per os to 10 patients with chronic hepatitis C in an open-label study that lasted 1 month. Every patient who entered the study had elevated liver enzyme levels, which at the end of study have decreased in 100% of analyzed patients. The reduction was highly significant, from 157.7+/-73.4 to 49.9+/-43.8 U/L (P=0.0013) and 147.0+/-79.2 to 58.7+/-56.6 U/L (P=0.0132), for ALT and AST, respectively. The AST/ALT ratio has improved from 0.93 to 1.18 (P=0.00058) indicating the reversion of progression to cirrhosis. None of intent-to-treat patients who were anti-HCV antibody positive at study entry, became negative after 1 month on V5 (P=0.998). All patients, except one, reported complete recuperation from hepatitis C-associated clinical symptoms present at baseline (P=0.0016) with Mantel Haenszel's odds ratio 9.4 (P=0.0021) at 95% confidence interval: 2.7<OR<476.3. No adverse events were observed at any time. The favorable biochemical and clinical responses have been observed in a small number of individuals for a limited time period. Larger scale and longer studies are needed to confirm our preliminary observations suggesting that V5 is safe and effective means for immunotherapy of chronic hepatitis C.


Effects of some centrally acting muscle relaxants on spinal root potentials: a comparative study.
The effects of intravenously administered mephenesin, tolperisone, baclofen, diazepam and midazolam on reflex activity were studied in unanesthetized spinal cats. Monosynaptic, as well as polysynaptic ventral root reflexes, the dorsal root potential and the dorsal root reflex were recorded simultaneously from L6-S1 segments. An analogue integrating method was developed for quantitative monitoring and recording ipsilateral spinal root potentials evoked by stimulation of the tibial nerve. Mephenesin (12.5-50 mg/kg) caused a significant and dose-dependent reduction in the polysynaptic and the dorsal root reflexes, slightly decreased the dorsal root potential but minimally affected the monosynaptic ventral root reflex. Tolperisone (2.5-10 mg/kg) dose-dependently inhibited both ventral root reflexes and the dorsal root reflex. It slightly prolonged the dorsal root potential without affecting the amplitude. Baclofen (0.5 mg/kg) abolished the monosynaptic reflex, partially inhibited the polysynaptic reflex, while dorsal root responses were less attenuated. Both benzodiazepines exerted similar actions, both qualitatively as well as quantitatively: the polysynaptic reflex was partially reduced while the monosynaptic reflex was not modified by diazepam or midazolam. Dorsal root responses were enhanced and the half-time of decay of the dorsal root potential was prolonged. Different patterns of action of muscle relaxants studied here are discussed in terms of their possible mechanisms of action. Profound depressant effects of mephenesin and tolperisone on the dorsal root reflex are in contrast to the small effect of both drugs on the dorsal root potential and might reflect their inhibition of spike-generating mechanisms. For a yet unknown reason, various spinal pathways are affected differentially by baclofen. In spinal cats, the reduction by benzodiazepines of the polysynaptic reflex may be related to the potentiation of some unidentified GABA-ergic inhibitory processes. The use of water-soluble midazolam, as a model compound instead of diazepam, is suggested because the usual organic solvents for diazepam may affect its action.


African swine fever virus: current state and future perspectives in vaccine and antiviral research.
African swine fever (ASF) is among the most significant of swine diseases for which no effective vaccines and antivirals are available. The disease, which is endemic in Africa, was introduced to Trans-Caucasian countries and the Russian Federation in 2007, where it remains prevalent today among domestic pigs and wild boars. Although some measures were implemented, ASF continues to pose a global risk for all countries, and thereby highlighting the importance of vaccine and antiviral research. In this review, an overview of research efforts toward the development of effective vaccines during the past decades is presented. As an alternative to vaccine development, the current state in antiviral research against ASFV is also presented. Finally, future perspectives in vaccine and antiviral research giving emphasis on some strategies that may allow researchers to develop effective countermeasures against ASF are discussed.


Core, secondary, and peripheral foods in the diets of Hispanic, Navajo, and Jemez Indian children.
Our results show the importance of a number of regional foods and suggest some differences in the dietary patterns of three ethnic groups in the same region. Dietitians and nutritionists should be aware of the rich ethnic diversity of dietary patterns and use this knowledge in nutrition counseling, program planning, and nutrition education.


The cultural bond? Cricket and the imperial mission.
Cricket tours provide an excellent insight into the relationship between the colonies and England during the Imperial era. New Zealand has never had much of a cricketing legacy, but the game was still cherished and English tours were enthusiastically followed because they provided a link with 'home'. Two English cricket teams visited New Zealand in the Edwardian age, the Lord Hawke XI in 1902-03 and the MCC in 1906-07. These tours were intended to be a panacea for a struggling local game while providing an extension of the cultural bonds of Empire. Both tours were rich in Imperial code and ceremony but their impact was lost in translation. The Lord Hawke XI, although all conquering, failed to win the hearts and minds of the New Zealand public because of a series of on-field moments of poor sportsmanship, and the public response to the treatment of the professionals in the team. The MCC team provided a fair challenge to New Zealand team, but lacked the star appeal of the Lord Hawke team, leaving the public somewhat underwhelmed. Both tours exemplify the difficulty in balancing the ideals inherent in the game with the realities of colonial sporting expectation.


Chemoprevention of neonatal jaundice: potency of tin-protoporphyrin in an animal model.
The substantial increases of hepatic, splenic, and renal heme oxygenase levels that occur shortly after birth in neonatal rats were prevented by a single administration of tin-protoporphyrin (10 micromoles per kilogram of body weight). With this treatment serum bilirubin levels declined within 24 hours to near-normal adult levels and remained low throughout the postnatal period. Zinc-protoporphyrin at doses up to 50-fold greater than the effective dose of tin-protoporphyrin did not prevent the immediate increases in tissue heme oxygenase activities and in serum bilirubin levels that occur postnatally. Studies in vitro with microsomal heme oxygenase in human spleen indicate that tin-protoporphyrin is a potent competitive inhibitor of the oxidation of heme to bile pigment in this tissue.


Diastereoselective synthesis of octahydro-14H-benzo[g]quinolino-[2,3-a]quinolidines. Improved cytotoxic activity against human brain tumor cell lines as a result of the increased rigidity of the molecular backbone.
Cis-Octahydro-14H-benzo[g]quinolino[2,3-a]quinolidines 6 were obtained in 6 steps from L-phenylalanine. The key step utilizes a diastereoselective intramolecular EtAlCl2-catalyzed hetero-Diels-Alder reaction. Compounds 6a-f were tested in vitro against human medulloblastoma D283 Med and glioblastoma A-172 and T98G cell lines and showed improved cytotoxicity compared to the corresponding, less rigid pyrido[1,2-b]isoquinolines 1.


MK-801 suppresses muricidal behavior but not locomotion in olfactory bulbectomized rats: involvement of NMDA receptors.
In rats, olfactory bulbectomy (OBX) causes changes in glutamatergic function in the amygdala (AMG) and induces mouse-killing behavior (MKB). The medial AMG (mAMG) plays an important role in the initiation and maintenance of OBX-induced MKB. In the present study, systemic injection or intra-mAMG perfusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) was used to determine the effects of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on the expression of OBX-induced MKB in male Wistar rats that had undergone OBX 1 month previously. The effects of MK-801 on locomotion in OBX rats were also examined using the open-field test. Intraperitoneal injection of MK-801 at doses of 0.10 and 0.15 mg/kg resulted in reversible suppression of MKB, the effect being maximal within 1 h after drug treatment, then gradually disappearing over 6 h. Locomotor distance in OBX rats was not affected using 0.10 mg/kg of MK-801, but increased after treatment with 0.15 mg/kg of MK-801; both doses, however, caused the rats to spend longer in the central area of the open field. MKB was also reversibly suppressed by local perfusion of 1 mM MK-801 at a rate of 1 microl/min into the mAMG through microdialysis probes. These results suggest that NMDA receptors, at least, in the mAMG, are involved in the expression of OBX-induced MKB.


Impact of salinity and pH on the UVC/H2O2 treatment of reverse osmosis concentrate produced from municipal wastewater reclamation.
While reverse osmosis (RO) technology is playing an increasingly important role in the reclamation of municipal wastewater, safe disposal of the resulting RO concentrate (ROC), which can have high levels of effluent organic pollutants, remains a challenge to the water industry. The potential of UVC/H(2)O(2) treatment for degrading the organic pollutants and increasing their biodegradability has been demonstrated in several studies, and in this work the impact of the water quality variables pH, salinity and initial organic concentration on the UVC/H(2)O(2) (3 mM) treatment of a municipal ROC was investigated. The reduction in chemical oxygen demand and dissolved organic carbon was markedly faster and greater under acidic conditions, and the treatment performance was apparently not affected by salinity as increasing the ROC salinity 4-fold had only minimal impact on organics reduction. The biodegradability of the ROC (as indicated by biodegradable dissolved organic carbon (BDOC) level) was at least doubled after 2 h UVC/H(2)O(2) treatment under various reaction conditions. However, the production of biodegradable intermediates was limited after 30 min treatment, which was associated with the depletion of the conjugated compounds. Overall, more than 80% of the DOC was removed after 2 h UVC/3 mM H(2)O(2) treatment followed by biological treatment (BDOC test) for the ROC at pH 4-8.5 and electrical conductivity up to 11.16 mS/cm. However, shorter UV irradiation time gave markedly higher energy efficiency (e.g., EE/O 50 kWh/m(3) at 30 min (63% DOC removal) cf. 112 kWh/m(3) at 2 h). No toxicity was detected for the treated ROC using Microtox(®) tests. Although the trihalomethane formation potential increased after the UVC/H(2)O(2) treatment, it was reduced to below that of the raw ROC after the biological treatment.


The humane society and the human-companion animal bond. Reflections on the broken bond.
This article discusses the history of the humane movement and how humane societies facilitate the human-companion animal bond by conducting various animal-protection programs (cruelty prevention, rescues, adoptions, veterinary services, for example) and participating in pet-facilitated therapy programs. Also discussed is the euthanasia of unwanted and unclaimed animals and its effect on animal shelter personnel.


Low vitamin D level is associated with higher relapse rate in natalizumab treated MS patients.
Previous research suggested a relationship between low vitamin D and relapse rate. We examined whether vitamin D levels were associated with: 1) MS severity and 2) recent MS relapse activity, in patients treated with natalizumab. All patients (n=118) were treated with natalizumab and were tested for vitamin D levels during the winter of 2009-10. Number of relapses during treatment with natalizumab was determined by retrospective chart review. MS severity was estimated with the Roxburgh's MS Severity Score (MSSS) at the time of the initial blood draw and 1 year preceding and following initial draws. Vitamin D levels of 50 nmol/L or greater were defined as normal. Patients with deficient vitamin D levels (DVD) totaled 45. Sixteen of the 26 patients with relapse in the year prior to the initial blood draw (4 patients had multiple relapses - all were in DVD) and 12 of 17 patients with relapse in the following year were in the DVD group. There was a significant difference between the normal vitamin D group (NVD) and DVD in MS relapse activity in the year prior (p=0.005) and following blood draw (p=0.006). There was no significant between group differences in MSSS at any time. Natalizumab treated patients with DVD were more likely to experience relapse and may experience more relapses than patients with NVD.


Demography of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) reared on elicitor-treated tomato plants with an innovative comparison of projected population sizes and application of the multinomial theorem for population survival.
Because of the considerable damage caused by tomato leafminer in tomato crops, the use of integrated methods is recommended. In this study, the effect of three different elicitors, methyl jasmonate, salicylic acid and ascorbic acid, on the life table parameters of Tuta absoluta was evaluated. A paired bootstrap test and different bootstrap percentiles were used to compare projected population sizes on specific dates. Survival probabilities were calculated by innovatively linking life tables and multinomial theorem. Preadult duration and mortality significantly increased, and the net reproductive rate (R0 ), intrinsic rate of increase (r), and finite rate of increase (λ) significantly decreased in all elicitor treatments. The lowest fecundity (F = 71.89 eggs/female) was observed in the salicylic acid treatment, with an R0 value of 13.48 offspring/individual, r of 0.0932 d-1 , and λ of 1.0977 d-1 . The population projection revealed the stage structure of T. absoluta during population growth, which was significantly reduced by the elicitor treatments. The survival probability of bootstrap samples was significantly lowered, whereas the extinction probabilities increased in elicitor treatments compared with control when the survival criterion was set to two fertile pairs. Our results demonstrated that the application of elicitors could reduce the risk of T. absoluta damage. Furthermore, population projection based on life tables is applicable to obtain the frequency distribution of the population size at different times. Combined application of life tables and multinomial theorem can be used to calculate the risk of pest emergence. © 2023 Society of Chemical Industry.