Extension as a prognostic factor in oropharyngeal cancer: largest mucosal dimension compared with number of (sub)sites involved.
We report a retrospective study of 64 patients with primary squamous cell carcinoma of the oropharynx. The tumours were classified by the UICC (Union Internationale Contre le Cancer) system and a New Tumour Staging (NTS) system. Results showed a crude survival of 29% at 5 years. The most important prognostic factor for survival rate was the tumour (T) stage in both classifications. NTS recommendations that consider the number of sites and subsites involved yield a better correlation between survival and T stage. NTS also discriminates better between the T stages than the UICC criteria.


Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells.
Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, which have been implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic physiologically constrained parametric search to identify the cellular mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We used heterogeneous model populations to ensure that our conclusions were not biased by parametric choices in a single hand-tuned model. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneities in synaptic plasticity profiles obtained with two different induction protocols. However, among the disparate forms of neural-circuit heterogeneities, our analyses demonstrated the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. We found that strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult neurogenesis-induced heterogeneities in neural structure were accounted for. Importantly, our analyses showed that it was not imperative that the manifestation of neural-circuit heterogeneities must translate to heterogeneities in plasticity profiles. Specifically, despite the expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable across all models through synergistic interactions among these heterogeneities. We assessed the parametric combinations required for the manifestation of such degeneracy in the expression of plasticity profiles. We found that immature cells showed physiological plasticity profiles despite receiving afferent inputs with weak synaptic strengths. Thus, the high intrinsic excitability of immature granule cells was sufficient to counterbalance their low excitatory drive in the expression of plasticity profile degeneracy. Together, our analyses demonstrate that disparate forms of neural-circuit heterogeneities could mechanistically drive plasticity heterogeneity, but also caution against treating neural-circuit heterogeneities as proxies for plasticity heterogeneity. Our study emphasizes the need for quantitatively characterizing the relationship between neural-circuit and plasticity heterogeneities across brain regions.


Establishment of Plantago lanceolata L. and Plantago major L. among grass : I. Significance of light for germination.
The influence of temperature, stratification, red/far-red ratio of the light (R/FR) and combinations of these factors on the germination of Plantago lanceolata and Plantago major ssp major have been investigated under controlled conditions. Only quantitative differences were found in the response of the species to the various environmental factors investigated except for germination in darkness. P. lanceolata germinated in darkness, the percentage depending on environmental factors and seed collection, whereas P. major seed swere found to have a virtually absolute light requirement. P. lanceolata germinated at lower temperatures and was less inhibited at a low R/FR than P. major. Pot experiments and a field experiment were carried out in order to study the influence of the presence of grass on germination and emergence. P. major was more inhibited than P. lanceolata when sown among grass and the presence of vegetation did not inhibit the germination of P. lanceolata in the field experiment. The latter could be ascribed to the dormancy alleviating effect of low winter temperatures to which the seeds had been subjected. The inhibition of emergence of P. major among grass could be explained by the light factor only, whereas in the case of P. lanceolata an additional factor must be involved.


Emergency Protective Measures and Strategies of COVID-19: From Lifestyle to Traditional Chinese Medicine.
This article reviews various aspects of COVID-19, including its current status, its side-effects, emergency protective measures and strategies from lifestyle to traditional Chinese medicine (TCM) for fighting against the SARS-CoV-2, and its major variants (Delta and Omicron), with the ongoing global COVID-19 pandemic, which include "Carassius auratus lifestyle" for high effective isolation, social and high-tech medical strategies, traditional Chinese herbs "Bark-Flower-Fruit-Grass-Leaf-Nucleolus(seed)-Root (BFFGLNR)", and the combination of Chinese and western medicine. As a choice, little is known whether the Chinese acupuncture is an effective method for confirming and suspecting COVID-19 patients, which include imported and asymptomatic cases. Definitely, acupuncture has been proven effective treatment for the recovery of COVID-19 cases. However, further animal experiments and clinical trials are required to confirm its effects and disclose underlying mechanisms. In conclusion, these emergency protective measures and strategies for COVID-19 will help to effectively combat the SARS-CoV-2 and its variants during the pandemic and post-COVID-19 era.


Human placental trophoblasts express the immunosuppressive cytokine IL-35.
Studies of maternal-fetal tolerance focus on defining mechanisms for establishment of immunological privilege within the uterus during pregnancy. Fetal trophoblasts play a key role in maternal tolerance, in part through cytokines production. As a novel inhibitory cytokine, IL-35 is produced by Foxp3(+) regulatory T cells (Tregs) and mediates maximal suppression of Tregs. The purpose of the study is to analyze the expression of IL-35 in first-trimester human placental trophoblasts. IL-35 expression was detected at both protein and mRNA levels by immunohistochemical staining and quantitative real-time PCR method, respectively and secretion of IL-35 was measured by ELISA assay. Our results demonstrated that human trophoblasts constitutively expressed IL-35. Ebi3 and p35 (two subunits of IL-35) mRNA was shown to be co-expressed in trophoblast cells. Moreover, large amounts of secreted IL-35 were detected in the supernatants of trophoblast cells. But we did not detect the constitutive expression of IL-35 in decidual stromal cells. Our findings confirmed for the first time that first-trimester human trophoblast cells expressed and secreted IL-35, which might contribute to their suppressive capacity to maternal immune cells. Therefore, IL-35 may be an important factor of the cytokine network regulating local immune responses during human pregnancy.


Impact of serial troponin release on outcomes in patients with acute heart failure: analysis from the PROTECT pilot study.
Cardiac troponin T (cTnT) elevation is common and is a predictor of outcomes in patients with acute heart failure (AHF). The degree and progression of cTnT release during hospitalization of patients with AHF is unclear. We evaluated the incidence of cTnT release during AHF hospitalization and the relationship of cTnT release with outcomes. The Placebo-controlled Randomized study of the selective A(1) adenosine receptor antagonist rolofylline for patients hospitalized with acute heart failure and volume Overload to assess Treatment Effect on Congestion and renal funcTion (PROTECT) pilot study was a multicenter, double-blind study of patients with AHF. Measurements of cTnT were collected at randomization and days 2, 3, 4, and 7. Patients were classified on the basis of their serum cTnT levels at baseline: positive (>0.03 ng/mL), detectable (>0.01 ng/mL), and negative (≤0.01 ng/mL). A detectable cTnT level developed during the study (after baseline) was classified as cTnT conversion: 288 patients were included; 172 (60%) patients had detectable cTnT levels and 97 (34%) had positive values (>0.03 ng/mL) at baseline. Of the 116 patients with negative troponin at baseline, 24 (21%) had elevated cTnT levels by day 7. On multivariable analysis, positive cTnT at baseline was an independent predictor of the composite end point of cardiovascular/renal rehospitalization or death at 60 days (hazard ratio, 1.84; 95% confidence interval, 1.04-3.26; P=0.036). Kaplan-Meier curves showed similar worse outcomes in patients with troponin conversion and positive troponin at baseline. There was a high prevalence of baseline cTnT elevation in this cohort; 21% of those negative at baseline converted to detectable levels by day 7. Positive troponin at baseline, and conversion to positive levels, were associated with worse outcomes at 60 days. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458.


Relationships between motor function and gait-related dual-task interference after stroke: a pilot study.
The purpose of this pilot study was to examine the relationships between motor performance measures and dual-task interference in gait among community-dwelling adults with stroke. Dual-task costs on gait were correlated with Fugl-Meyer lower extremity score and usual gait speed in 13 community-dwelling adults with stroke. Individuals with greater lower extremity motor impairment and slower gait speed experienced greater cognitive-motor interference in gait. Paretic single limb stance was particularly susceptible to dual-task interference. Gait speed was only vulnerable to dual-task interference in the most complex dual-task. Thus, global characteristics of gait were vulnerable in the most difficult cognitive tasks, but even easy tasks impaired discrete components of dynamic balance.


Calcium homeostasis change in CD4+ T lymphocytes from human peripheral blood during differentiation in vivo.
Resting naïve CD4+(CD45R0-)CD45RA+ T cells are sensitive to ionomycin. In contrast, resting CD4+(CD45RA-)CD45R0+ memory T cells show resistance to this Ca2+ ionophore. In the present study, the ability of activated T lymphocytes to respond to ionomycin during the transition from naïve precursors into memory T cells has been analyzed. Activated CD4+(CD45RA+)CD45R0+ T cells are always present both in human peripheral blood (HPB) and in the ionomycin-resistant (IR) fraction. Therefore, some activated T cells are resistant toward the Ca2+ ionophore. CD69 molecules are markers of the very early stage of T cell activation. However, CD4+CD69+ T cells have never been found in the IR fraction. Thus, the majority of CD4+ T lymphocytes at the early stage of activation are ionomycin-sensitive cells. The proportion of CD4+CD25+ T cells did not differ significantly in HPB and in the IR fraction. The presence of CD4+CD25+ T lymphocytes in the IR fraction reflects changes in the Ca2+-signaling pathway at this differentiation step of activated cells. Depending on the expression level of CD25 molecules, the population of CD4+CD25+ cells is divided in T-regulatory (CD25high) and proliferating (CD25low) subpopulations. The action of ionomycin results in a decrease in the portion of the CD4+CD25low T-cells, but it leads to an increase in the proportion of the CD4+CD25high T lymphocytes. Consequently, greater portion of CD4+CD25high T lymphocytes and smaller portion of CD4+CD25low T cells are IR cells. Expression of HLA-DR molecules can be used as the marker for the late activation step. The IR fraction is significantly rich in CD4+HLA-DR+ T lymphocytes in comparison to the blood of the same donor. The link between different differentiation steps of CD4+ T-lymphocytes and alterations in calcium ion homeostasis is discussed.


COVID-19 pneumonia accurately detected on chest radiographs with artificial intelligence.
To investigate the diagnostic performance of an Artificial Intelligence (AI) system for detection of COVID-19 in chest radiographs (CXR), and compare results to those of physicians working alone, or with AI support. An AI system was fine-tuned to discriminate confirmed COVID-19 pneumonia, from other viral and bacterial pneumonia and non-pneumonia patients and used to review 302 CXR images from adult patients retrospectively sourced from nine different databases. Fifty-four physicians blind to diagnosis, were invited to interpret images under identical conditions in a test set, and randomly assigned either to receive or not receive support from the AI system. Comparisons were then made between diagnostic performance of physicians working with and without AI support. AI system performance was evaluated using the area under the receiver operating characteristic (AUROC), and sensitivity and specificity of physician performance compared to that of the AI system. Discrimination by the AI system of COVID-19 pneumonia showed an AUROC curve of 0.96 in the validation and 0.83 in the external test set, respectively. The AI system outperformed physicians in the AUROC overall (70% increase in sensitivity and 1% increase in specificity, p < 0.0001). When working with AI support, physicians increased their diagnostic sensitivity from 47% to 61% (p < 0.001), although specificity decreased from 79% to 75% (p = 0.007). Our results suggest interpreting chest radiographs (CXR) supported by AI, increases physician diagnostic sensitivity for COVID-19 detection. This approach involving a human-machine partnership may help expedite triaging efforts and improve resource allocation in the current crisis.


Use of magnetic resonance imaging in planning the separation of omphalopagus conjoined twins.
Magnetic resonance imaging (MRI) was used for the first time in the preoperative planning for separation of conjoined twins. In these omphalopagus infants, MRI showed normal biliary and cardiovascular structures and demonstrated, in detail, a relatively avascular plane through the liver bridge, which enabled safe separation with minimal blood loss at 3 1/2 months of age. A single MRI study supplied information superior to that obtained with multiple previously available imaging studies. MRI should be an essential part of the preoperative workup of all types of conjoined twins.


Hypoxia enhances the protective effects of placenta-derived mesenchymal stem cells against scar formation through hypoxia-inducible factor-1α.
To explore the effect of placenta-derived mesenchymal stem cells on scar formation as well as the underlying mechanism. The isolated placenta-derived mesenchymal stem cells from mice were distributed in the wounded areas of scalded mouse models, attenuated inflammatory responses and decreased the deposition of collagens, thus performing a beneficial effect against scar formation. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells and hypoxia-inducible factor-1α was involved in the protective effect of placenta-derived mesenchymal stem cells in hypoxic condition. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells through hypoxia-inducible factor-1α and PMSCs may have a potential application in the treatment of wound.


Therapeutic potential of curcumin in diabetic complications.
Diabetes mellitus is an extremely prevalent endocrine disease and a major global public health concern. Diabetic complications, such as retinopathy, nephropathy, neuropathy and cardiovascular disease, are common and majorly impact a patient's quality of life. Curcumin, the major active component of turmeric, possesses extensive known pharmacological properties, including anti-inflammatory, antioxidant, and antitumor effects. Increasing evidence suggests that curcumin may offer protection against diabetic complications. The current review focuses on the possible molecular targets and pathways involved in diabetic complications and, in particular, the multi-target approach of curcumin in attenuating diabetic nephropathy, retinopathy, and neuropathy.


A semantic memory sentence verification model based on relative judgment theory.
A subjective referent model of sentence verification in semantic memory tasks based on the relative judgment theory of Link and Heath (1975), together with the derivation of a discriminability index, are presented in this paper. An attractive feature of the model is its consideration of both error rates and response times (RTs) in the calculation of the discriminability index. The model is also able to account for the frequent finding in semantic memory tasks that error RTs are longer than correct RTs. A partial replication of Experiment 2 of McCloskey and Glucksberg's (1979) sentence verification context effect studies, in which we employed 44 subjects and 28 categories, and controlled for item familiarity, revealed that error RTs were consistently longer than correct RTs--a finding inconsistent with the McCloskey and Glucksberg property comparison model, but in accord with the subjective referent model. An important fortuitous result was the detection of a context effect by the discriminability measure, an effect not detected by the RT data alone. The discriminability measures yielded a near perfect correlation with estimates of the mean step size of the random walk obtained by application of the parameter estimation program FITTRW (Heath, 1983).


Plasma spermine concentrations of patients with benign and malignant tumours of the breast or prostate.
A radioimmunoassay has been developed for the measurement of plasma spermine concentrations. The sensitivity of the method is 1 pmol spermine/100 microliters plasma and the crossreactivity was 12% with spermidine and 0.18% with putrescine. Plasma spermine levels of patients with benign and malignant tumours of the prostate or breast were measured using this technique. Concentrations were only occasionally elevated in patients with prostatic tumours compared to normal individuals and there was no difference between those men with benign (mean concn. 0.21 +/- 0.14 nmol/ml plasma) or malignant (mean concn. 0.21 +/- 0.11 nmol/ml plasma) tumours. Only 17% of the patients with breast carcinoma had elevated levels of spermine, although there was a significant difference in the concentrations of the breast cancer group of patients compared to normals. No correlation was found between elevated plasma spermine concentrations and tumour grade or presence or spread of metastases in those patients.


"Umpolung" photoinduced charge separation in an anion-bound supramolecular complex.
A new supramolecular system, consisting of an expanded porphyrin, cyclo[8]pyrrole (C8) and a pyrene carboxylate (Py) is capable not only of electron transfer upon photoexcitation, but results in "umpolung" or a reversal of the predicted charge-separation behavior in that the higher energy radical ion pair, C8.+-Py.- (2.58 eV) is formed as opposed to C8.--Py.+ (1.31 eV). This observation is rationalized in terms of the latter radical ion pair, C8.--Py.+ being in the Marcus inverted region. Transient absorption spectral studies reveal a charge-separated lifetime of 300 micros, which decays to the triplet state of cyclo[8]pyrrole, also an exceedingly long-lived species. The novel features of this noncovalent dyad highlight the potential utility of anion binding in the construction of supramolecular electron transfer systems.


The SP1 antigen in subplate neurons of the developing cat cortex is an immunoglobulin-like molecule.
Monoclonal antibody subplate-1 (mAb SP1) specifically stains somata, dendrites and axons of spiny inverted pyramidal neurons in the subplate zone in the early postnatal kitten neocortex. The SP1 antigen has been previously identified as a cytosolic protein of apparent molecular weight 56 kDa. We have now employed immune-affinity chromatography to further characterize this antigen. An antigen with SP1-like immunoreactivity (ir) is present in various organs, and is particularly enriched in blood plasma. Exsanguination of the organs prior to protein extraction reduces the SP1-ir band dramatically, indicative of a blood-borne molecule. The 56 kDa SP1-ir antigen was purified from plasma by affinity chromatography and subjected to Edman degradation. The first 20 N-terminal amino acids show 80% homology to the N-terminus of immunoglobulin heavy chain of man, the mouse and the dog. If the 56 kDa SP1-ir antigen in plasma is an immunoglobulin, and if an immunoglobulin-like molecule is present in the subplate, then antisera against cat immunoglobulins should stain subplate neurons. A polyclonal antiserum against cat IgG intensely stains the somata and dendrites of subplate neurons. On protein blots, this antiserum recognizes the 56 kDa band, and an additional band of approximately 27 kDa, corresponding in size to immunoglobulin light chains. Preabsorbing mAb SP1 with cat immunoglobulin G abolishes the immunoreactivity in sections of kitten cortex. Further, it dramatically reduces the reactivity on protein blots. The results suggest that the 56 kDa SP1-ir antigen in cortical subplate neurons belongs to the immunoglobulin superfamily.


Increased hand digit length ratio (2D:4D) is associated with increased severity of hypospadias in pre-pubertal boys.
Hypospadias is a common congenital male disorder, with much research focusing on prenatal androgen exposure as a causative factor. Whilst digit length ratios were apparent in sexual dimorphism since the nineteenth century, their role in hypospadias remains unknown. The objective of our study was to determine the correlation between digit length (2D:4D) ratio, hypospadias severity, and anogenital distance. Pre-pubertal boys (<3 years old) seen intra/postoperatively following hypospadias repair (June 2018-January 2019 inc.) were included. These were age-matched to non-hypospadias controls. Anthropomorphic measurements of digit lengths, penile/glans width, and anogenital distance were measured using digital calipers. Data measurements were collected for 105 boys with hypospadias (60 distal; 45 proximal) and 55 controls. There were significant differences in 2D:4D ratios in each hand (p < 0.001), as well as individual digits (p < 0.001), and a reduced anogenital distance (p < 0.001), when comparing the proximal group with distal or control groups. There were no significant differences in glans width, or between term- and preterm births. This study is the first to demonstrate increased 2D:4D ratios with proximal hypospadias, which also correlate with a shortened anogenital distance. This may provide a non-invasive, potentially antenatal, anthropomorphic measurement, as an indirect indicator of aberrant urogenital development.


Neonatal hip septic arthritis: ultrasound should not influence decision to aspirate.
An 18-week-old boy presented to the emergency department with 24-h history of fever and irritability with a painful left hip held in flexion. Blood tests showed an elevated ESR of 65 mm/h, but white cell count and C-reactive protein were in the reference range. Admission hip ultrasound identified a small effusion (<2 mm at the recess), not large enough to determine turbidity. Joint aspiration under general anaesthesia yielded frank pus and mandated open arthrotomy. Physicians must maintain a high index of suspicion of hip septic arthritis irrespective of ultrasound findings and have a low threshold for joint aspiration. Aspiration 'to dryness' would have left substantial pus within the joint and is consistent with advocating arthrotomy and washout in this age group, when the diagnosis of septic arthritis has been made.


Seizure-induced neutrophil adhesion in brain capillaries leads to a decrease in postictal cerebral blood flow.
Cerebral hypoperfusion has been proposed as a potential cause of postictal neurological dysfunction in epilepsy, but its underlying mechanism is still unclear. We show that a 30% reduction in postictal cerebral blood flow (CBF) has two contributing factors: the early hypoperfusion up to ∼30 min post-seizure was mainly induced by arteriolar constriction, while the hypoperfusion that persisted for over an hour was due to increased capillary stalling induced by neutrophil adhesion to brain capillaries, decreased red blood cell (RBC) flow accompanied by constriction of capillaries and venules, and elevated intercellular adhesion molecule-1 (ICAM-1) expression. Administration of antibodies against the neutrophil marker Ly6G and against LFA-1, which mediates adhesive interactions with ICAM-1, prevented neutrophil adhesion and recovered the prolonged CBF reductions to control levels. Our findings provide evidence that seizure-induced neutrophil adhesion to cerebral microvessels via ICAM-1 leads to prolonged postictal hypoperfusion, which may underlie neurological dysfunction in epilepsy.


Management of Early Parkinson Disease.
Early Parkinson disease is the approximate time period between initial diagnosis and the onset of motor fluctuations. Treatment requires an integrative approach, including identification of motor and nonmotor symptoms, choice of pharmacologic treatment, and emphasis on exercise. Patients should be treated for motor symptoms, whereas medications may be delayed for milder symptoms. The choice of treatment in patients with early Parkinson disease must be weighed against financial considerations, ease of administration, and potential long-term adverse events. Nonmotor symptoms should also be identified and treated. Exercise is an important component for treatment of Parkinson disease at any stage.


Corneal thickness measurements: scanning-slit corneal topography and noncontact specular microscopy versus ultrasonic pachymetry.
To compare central corneal thickness measurements taken with 3 pachymetry systems: Orbscan scanning-slit corneal topography/pachymetry, Topcon SP2000P noncontact specular microscopy, and Tomey ultrasonic pachymetry. Multicenter study, Tokyo, Japan. In 216 healthy eyes of 114 subjects, scanning-slit topography, noncontact specular microscopy, and ultrasonic pachymetry were used in that sequence to record central corneal thickness. In another 20 healthy eyes of 13 subjects, 2 sets of measurements were repeated for each pachymetry to assess repeatability. The mean central corneal thickness was compatible between scanning-slit topography (546.9 micrometers +/- 35.4 [SD] ) and ultrasonic pachymetry (548.1 +/- 33.0 micrometers); however, noncontact specular microscopy gave a significantly smaller mean (525.3 +/- 31.4 micrometers) than the other 2 tests (P<.001, Tukey multiple comparison). There were significant linear correlations between scanning-slit topography and noncontact specular microscopy (r = 0.846, P<.001), noncontact specular microscopy and ultrasonic pachymetry (r = 0.897, P<.001), and ultrasonic pachymetry and scanning-slit topography (r = 0.852, P<.001). Noncontact specular microscopy tended to show the best repeatability; however, the difference was not statistically significant (P =.663, repeated-measure analysis of variance). Corneal thickness readings were comparable between scanning-slit topography and pachymetry; noncontact specular microscopy gave significantly smaller values. The measurements of the 3 methods showed significant linear correlations with one another. All methods provided acceptable repeatability of measurements.


[Comparative evaluation of the hypolipidemic action of sunflower oil and "Zdorov'e" margarine incorporated into the anti-atherosclerotic diet of ischemic heart disease patients].
Patients with ischemic heart disease attended by type II hyperlipidemia received diets containing sunflower oil (group I) or margarine "Zdorovie" (group II) as a source of poly-unsaturated fatty acids. Pronounced reduction of the blood cholesterol level was recorded in both groups of patients studied. Margarine "Zdorovie" is recommended for subjects intolerant to vegetable oils.


A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination.
Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cell's genome stability by orchestrating the repair of interstrand cross-linking during the S phase of the cell cycle, preventing the chromosomal instability that is a key event in bone marrow failure syndrome. Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins. Each protein, when mutated, can cause FA. The FA core-complex-catalyzed reaction is critical for signaling DNA cross-link damage such as that induced by chemotherapies. Here, we present a perspective on the current understanding of FANCI and FANCD2 monoubiquitination-mediated DNA repair. Our recent biochemical reconstitution of the monoubiquitination (and deubiquitination) reactions creates a paradigm for understanding FA. Further biochemical analysis will create new opportunities to address the leukemic phenotype of FA patients.


Stair climbing: an alternative exercise modality for firefighters.
The purpose of this investigation was to determine the maximal cardiorespiratory responses of firefighters to stair-climbing work and to compare these responses to maximal treadmill exercise. Thirty-eight firefighters volunteered to participate in the study. Maximal CR including oxygen consumption (VO2), ventilatory equivalent for oxygen (VE/VO2), minute ventilation (VE) and heart rate (HR) were measured during both stair climbing and graded treadmill exercise. The results showed that VO2max and HRmax were significantly lower, 7% and 2% respectively, and the VE/VO2 was significantly higher (6.7%) during the stair-climbing exercise. Maximal VE was not different between the two modes of exercise. The results suggest that since VO2max and HRmax were lower during stair climbing, the metabolic cost of firefighting tasks as related to VO2max on a treadmill may not be accurately reflected. Since stair climbing is a task-specific activity for firefighters, it is recommended that testing of firefighters be performed on a stair-climbing device, and that the difference in VO2max between treadmill and stair-climbing exercise be considered when recommending a desired fitness level for firefighters.


The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer.
The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen. BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM. The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.


Changing to generic formulary: how one fundholding practice reduced prescribing costs.
To observe one general practice's attempt to reduce prescribing costs on becoming third wave fundholders through the introduction of a generic formulary applied to all new and repeat prescribing. To assess the impact on patients and prescribing patterns. An observational study using interviews with patients and practitioners; questionnaires for patients and prescribing data. One urban general practice with five partners in Scotland. It became fundholding in April 1993. 71 searches of the register of repeat prescriptions identified 1274 potential changes in drugs. Questionnaires were sent to a stratified random sample of 280 patients four months after the changes were made; 33 interviews were conducted with 17 patients selected by local pharmacists to represent a wide range of opinion. Changes in prescribing and response and satisfaction of patients. Of intended changes, 129 (70%) were in place after four months. Thirty three (20%) of the 167 patients who returned questionnaires were "very unhappy," though interviews suggested that this was primarily with the communication they received rather than the change itself. Generic prescribing rose from one in three (37%) to over a half (58%). The volume of treatment dispensed (as treatment days) fell by 67,674 (10.7%), and the average cost per day's treatment fell by 3.1 p from 32.3 p per day in 1992 (9.4%), producing a total absolute saving of 24% (137,712 pounds) over the first year. This practice has achieved a large reduction in prescribing costs rapidly. These were tolerated by patients, none of whom is thought to have left the practice for this reason. Great care must be taken to inform patients appropriately.


Plasma free N-terminal fibronectin 30-kDa domain as a marker of endothelial dysfunction in type 1 diabetes mellitus.
The plasma free N-terminal fibronectin 30-kDa domain was measured in 44 type 1 diabetic patients and in 20 healthy subjects. A significantly raised mean concentration of a free N-terminal fibronectin 30-kDa domain was found in plasma of diabetic patients with proliferative retinopathy as compared with healthy persons (P less than 0.001). A positive correlation was observed between free N-terminal fibronectin 30-kDa domain and von Willebrand factor in plasma of all examined subjects (r = 0.62, P less than 0.01). A similar correlation was present between 30-kDa domain and albuminuria (r = 0.56, P less than 0.01). However, no relationship was found between fibronectin 30-kDa domain and control of diabetes as assessed by fructosamine concentration. The free N-terminal fibronectin 30-kDa domain may be used as a marker of actual endothelial cell dysfunction in diabetes.


[Anaphylactic reaction after soya intake in a patient with birch pollen allergy].
Patients with birch pollen allergy may suffer from severe anaphylactic reactions after ingestion of foodstuffs containing soya. The reason for this is similarities in protein structure between a major birch pollen allergen (bet v 1) and Gly m 4, a pollen-related protein in soya. A 65-year-old patient allergic to birch pollen developed an adverse systemic reaction after consumption of a soya-containing drink. The diagnosis could be confirmed by in vitro and skin testing methods. Patients who suffer from birch pollen allergy should strictly avoid the intake of soya-containing foodstuffs.


Latency in the inositol lipid transduction pathway: the role of cellular events in responses to thyrotropin-releasing hormone in Xenopus oocytes.
To dissect the cellular events responsible for the prolonged latency of the response to thyrotropin-releasing hormone (TRH) in Xenopus oocytes we interfered with different steps of the signal transduction pathway. Preincubation of oocytes with cis-vaccenic acid (a membrane-fluidizing agent) shortened the latency, suggesting a contribution of membranal processes. TRH-induced depletion of cellular calcium stores prolonged latency (up to threefold), which returned to control levels upon repletion of the stores. Injection of D-2,3-diphosphoglycerate (PGA), which inhibits inositol (1,4,5)-trisphosphate (InsP3) dephosphorylation, alone evoked a small, prolonged depolarizing current and significantly shortened the latency of the response to TRH. Injection of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which inactivates guanine nucleotide-binding regulatory proteins, decreased the amplitude of the response and increased latency. Injection of guanosine 5-O-(3-thiotriphosphate) (GTP gamma S) immediately before the challenge with TRH did not shorten the latency of the response. Decreasing the effective receptor density with chlordiazepoxide, an antagonist of the TRH receptor, resulted in an extension of latency, whereas the expression of a large number of TRH receptors by injection of RNA transcribed from cloned receptor DNA (10-100 ng/oocyte) shortened the latency to below 2 s. Our results suggest that the latency of the response to TRH reflects the activation of a late step in the signal transduction sequence, most likely the release of calcium by InsP3. We propose that this process is kinetically controlled by an early rate-limiting event, involving the activation of a guanine nucleotide-binding protein by the TRH receptor.


The impact of early surgical treatment of tracheal stenosis on neurorehabilitation outcome in patients with severe acquired brain injury.
Acquired tracheal stenosis (TS) is a potentially life-threatening condition following prolonged intubation and/or tracheostomy in adult patients with severe Acquired Brain Injury (sABI), requiring a tracheal resection and reconstruction. We included 38 sABI adult patients with TS, admitted at a post-acute Neurorehabilitation Hospital. Disability Rating Scale (DRS) and other functional assessment measures were recorded at admission (t1), before TS surgical treatment (t2), and at discharge (t3). Patients were defined as 'improved' when they changed from a more severe to a less severe disability, between time t2 and time t3, and as "not improved" when they did not show any further improvement between t2 and t3, or they already exhibited a disability improvement since time interval t1-t2. Time interval between the injury onset and TS surgical treatment (t2-t0) was associated with the patient's disability improvement, suggesting the t2-t0 time interval ≤ 115 days as a cutoff value for a possible functional recovery. A t2-t0 time interval ≤ 170 days is also associated to absence of persistent dysphagia. Early TS surgical treatment within 115 days from the injury onset contributes to the improvement of the disability level in patients with sABI, optimizing their functional outcomes and recovery potential.


The prophylactic use of antibiotics in cell culture.
This article describes the historical development of the prophylactic use of antibiotics in cell culture as well as their effects on cells. The influence of antibiotics on cell morphology, cellular degeneration and cell death and cellular function is summarized. Cellular DNA as well as protein synthesis are affected which can lead to interference with, or even changes in, metabolic processes. Such effects must be considered in cell culture research. As antibiotics are used in multifold ways, the otherwise standardized conditions in cell culture are no longer comparable. The prophylactic use of antibiotics is rejected for scientific reasons.


Amino acid functionalized boron nitride nanosheets towards enhanced thermal and mechanical performance of epoxy composite.
The practical applications of boron nitride nanosheet (BNNS) are dramatically limited by the harsh exfoliation and surface functionalization conditions due to the hydrophobic and chemically inert nature. This issue can be improved by selecting efficient modifiers with hydrophilic groups. A green and scalable amino acid-assisted ball milling method is presented to exfoliate and functionalize BNNS simultaneously. The different interactions between BNNS and four amino acids (tryptophan (Trp), phenylalanine (Phe), arginine (Arg), lysine (Lys)) are thoroughly investigated to rationalize the thermal and mechanical properties of their corresponding epoxy (EP) composites. Trp and Phe display higher functionalization degree and dispersibility of BNNS than Arg and Lys thanks to the additional π-π interactions between the aromatic groups and BNNS. Moreover, both BNNS-Trp/EP and BNNS-Phe/EP exhibit higher cross-plane thermal conductivity of 2.1 and 1.96 W m-1 K-1 at 30 wt% filler loading. In addition, the mechanical strengths of all these amino acids functionalized BNNS filled epoxy composites are significantly enhanced due to stronger interfacial interactions between fillers and epoxy matrix. Thus, this work paves the way for the facile mass production of functionalized BNNS and expedites their applications in thermal interface materials of electronic components.


Tooth Wear Evaluation System (TWES) 2.0-Reliability of diagnosis with and without computer-assisted evaluation.
Tooth wear is a multifactorial process, leading to the loss of dental hard tissues. Therefore, it is important to detect the level of tooth wear at an early stage, so monitoring can be initiated. The Tooth Wear Evaluation System (TWES) enables such a multistage diagnosis of tooth wear. The further developed TWES 2.0 contains a complete taxonomy of tooth wear, but its reliability has not yet been validated. The aim of the study was to examine in a randomised controlled trial (RCT) whether diagnoses made based on the TWES 2.0 are reproducible and whether this reproducibility is also achieved with computer-assisted diagnostics. 44 dental students received extensive training in TWES 2.0 assessment and taxonomy. The students each evaluated at least 10 (of the present 14) anonymised patient cases using gypsum models and high-resolution intra-oral photographs according to TWES 2.0. One half initially evaluated on paper; the other half used dedicated software (CMDfact / CMDbrux). After half of the patient cases (5), the evaluation methods were switched (AB/BA crossover design). The diagnoses were then evaluated for agreement with the predefined sample solution. Evaluation of agreement with the sample solution according to Cohen's kappa indicated a value of 0.46 for manual (traditional) evaluation; and 0.44 for computer-assisted evaluation. Evaluation of agreement between examiners was 0.38 for manual and 0.48 for computer-assisted evaluation (Fleiss' kappa). The results of this study proved that the taxonomy of the TWES 2.0 has acceptable reliability and can thus be used by dentists. Accordingly, the system can be learned quickly even by untrained practitioners. Comparable results are achieved with computer-assisted evaluation.


Jasmine: a Java pipeline for isomiR characterization in miRNA-Seq Data.
The existence of complex subpopulations of miRNA isoforms, or isomiRs, is well established. While many tools exist for investigating isomiR populations, they differ in how they characterize an isomiR, making it difficult to compare results across different tools. Thus, there is a need for a more comprehensive and systematic standard for defining isomiRs. Such a standard would allow investigation of isomiR population structure in progressively more refined sub-populations, permitting the identification of more subtle changes between conditions and leading to an improved understanding of the processes that generate these differences. We developed Jasmine, a software tool that incorporates a hierarchal framework for characterizing isomiR populations. Jasmine is a Java application that can process raw read data in fastq/fasta format, or mapped reads in SAM format to produce a detailed characterization of isomiR populations. Thus, Jasmine can reveal structure not apparent in a standard miRNA-Seq analysis pipeline. Jasmine is implemented in Java and R and freely available at bitbucket https://bitbucket.org/bipous/jasmine/src/master/. Supplementary data are available at Bioinformatics online.


Involvement of BglG in Lipopolysaccharides (LPS) Synthesis and Transport in Stationary Phase in E. coli.
BglG, an RNA binding regulatory protein encoded by the β-glucoside (bgl) operon of E. coli is known to be involved in the regulation of several metabolic functions in stationary phase. A genome-wide comparative transcriptome analysis performed earlier between a ∆bglG strain and its isogenic WT counterpart revealed that genes involved in lipopolysaccharide (LPS) biosynthesis and transport were significantly down-regulated in the absence of BglG in stationary phase, suggesting a role for BglG in their regulation. We have investigated the involvement of BglG in LPS biosynthesis and transport. Consistent with the down-regulation of LPS synthesis and transport genes, the ∆bglG strain showed a loss of permeability barrier specifically in stationary phase, which could be rescued by introduction of wild type bglG on a plasmid. A search for a putative transcription factor involved in the regulation mediated by BglG led to the identification of GadE, which is one of the primary positive regulators of pH homeostasis and LPS core biosynthesis. Using RNA mobility shift and stability assays, we show that BglG binds specifically to gadE mRNA and enhances its stability. Consistent with this, loss of gadE leads to a partial defect in permeability. Based on our findings, we propose a model for the molecular mechanism involved in the regulation on LPS synthesis and transport by BglG.


Management of esophageal atresia and tracheoesophageal fistula.
We can draw several conclusions from an analysis of our series: 1. Although prematurity remains to be an important factor in the survival of infants with major surgical or medical disease, the more important risk factor in esophageal atresia and tracheoesophageal fistula concerns: a. Severity of associated anomalies that are uncorrectable and fatal b. Associated complication from the disease or surgery (especially in infants less than 1500 gm). Complications such as tracheal perforation and gastric perforation are not tolerated well and can be fatal (the case in two of our patients). 2. Premature infants weighing even less than 1500 gm tolerate a major thoracotomy well with correction of an esophageal anomaly. In this series, the smallest weighed 1220 gm. This infant had an uneventful recovery with a good outcome. 3. Simultaneous correction of associated anomalies also is well tolerated by these patients. Judgment, however, should be exercised as to the extent and length of operative procedures performed. 4. Staged reconstruction is still an excellent alternative when one is dealing with a premature infant with concomitant surgical procedures, although lengthening operations with primary anastomosis for the most part have replaced the need for staging esophageal reconstruction. 5. Radiographs indicating a high upper pouch lesion also require bronchoscopic identification of the fistula prior to operative intervention to provide a guide to the proper surgical approach to the lesion. 6. Acute anastomotic leaks should be treated aggressively by antibiotics and immediate thoracotomy, with cervical esophagostomy, closure of the distal esophagus, drainage of the mediastinum, and gastrostomy placement. immediate intervention will result in better survival.(ABSTRACT TRUNCATED AT 250 WORDS)


How to live in colonies: spatial foraging strategies of the black-headed gull.
This paper describes some spatial foraging strategies observed in the course of the breeding season in five adult radio-tagged black-headed gulss (Larus ridibundus). 1. Individual foraging distances increased continuously during the nesting period. 2. The maximum foraging distance observed was 18.5 km. 3. All birds showed nearly constant flight directions over the whole breeding period. 4. It is suggested that the continuous increase in foraging distances reduces intraspecific competition around the colony. 5. Because of long foraging distances it seems to be advantageous to use only a small constant foraging sector. This behaviour can probably optimize spatial memory and enhance energetic and temporal efficiency.


The response to analgesia testing is affected by gonadal steroids in the rat.
The effect of gonadal steroids on the response to analgesia testing was determined in castrated male and female rats and castrated male and female rats treated with testosterone propionate (TP) and estradiol benzoate (EB), respectively. The time to respond to a noxious somatic stimulus in the form of heat was assessed using the tail withdrawal test (tail withdrawal from hot water) and hot plate test (the time to paw lick or jump). In male rats, castration resulted in a significant reduction of the reaction time for tail withdrawal. This effect was reversed by treatment with TP. The time to paw lick or jump in male rats was also diminished by castration. Treatment with TP resulted in a partial reversal of the effect of castration on this response. In castrated female rats, the time required for tail withdrawal was decreased by castration and increased by treatment with EB. The reaction time to the hot plate in female rats was diminished by castration and further reduced by EB administration. These data indicate that gonadal steroids influence the response to a noxious heat stimulus in male and female rats and that the effect may vary according to sex and the way in which the stimulus is applied.


Activated protein C resistance determined with a thrombin generation-based test is associated with thrombotic events in patients with lupus anticoagulants.
Several studies suggest that antiphospholipid antibodies interfere with the activity of activated protein C (APC). This acquired form of APC resistance has been proposed as a possible pathogenic mechanism underlying hypercoagulability associated with the antiphospholipid syndrome (APS). We wanted to investigate the inhibitory effect of recombinant APC (rAPC) on ex vivo thrombin generation in plasma and the modification of this effect by the presence of lupus anticoagulants (LA). We analyzed plasmas from 81 patients with LA (52 patients fulfilling the criteria for the APS) and 91 controls. Percent inhibition of the endogenous thrombin potential (ETP) as a parameter of APC sensitivity was determined in plasmas using a thrombin generation-based APC resistance test probed with rAPC. All results were normalized using pooled normal plasma (PNP) as a reference. Normalized percent inhibition of ETP by APC was lower in patients with LA [61.4%, 95% confidence interval (CI) 45.8-74.5%] compared to controls (107.8%, 95% CI: 107.1-109.3%). In patients with LA and APS, median inhibition was lower than in patients with LA without APS (44.6%, 95% CI: 30.1-55.7% vs. 78.8%, 95% CI: 73.9-95.8%). This difference also persisted when patients on warfarin therapy were excluded from the APS subgroup. APC resistance can be demonstrated with a thrombin generation-based test in a majority of patients with the LA laboratory phenotype. A history of thrombotic events in patients with LA is associated with a stronger resistance to the anticoagulant effect of APC.


Complex structural features of satellite DNA sequences in the genus Pimelia (Coleoptera: Tenebrionidae): random differential amplification from a common 'satellite DNA library'.
The major satellites of the nine species of the subgenera Pimelia s. str. and Amblyptera characterised in this paper are composed of longer monomers (500 and 700 bp) than those described previously in 26 Pimelia s. str. taxa (357 bp, a sequence called PIM357). Sequence analysis reveals partial similarity among these satellites and with the PIM357 monomers. The discrepancy between the phylogeny obtained based on three mitochondrial and two nuclear markers and that deduced from satellite DNA (stDNA) sequences suggests that the different Pimelia satellites were already present in a common ancestor forming what has been called a 'satellite DNA library'. Thus, the satellite profiles in the living species result from a random amplification of sequences from that 'library' during diversification of the species. However, species-specific turnover in the sequences has occurred at different rates. They have included abrupt replacements, a gradual divergence and, in other cases, no apparent change in sequence composition over a considerable evolutionary time. The results also suggest a common evolutionary origin of all these Pimelia satellite sequences, involving several rearrangements. We propose that the repeat unit of about 500 bp has originated from the insertion of a DNA fragment of 141 bp into the PIM357 unit. The 705-bp repeats have originated from a 32-bp direct duplication and the insertion of a 141-bp fragment in inverted orientation relative to a basic structure of 533 bp.


Changes in outpatient lithium treatment in the Netherlands during 1996-2005.
The objectives of the present study were to investigate in outpatients in the Netherlands between 1996 and 2005, changes in 1) the incidence and prevalence of lithium use and 2) lithium use patterns (discontinuation, add-on, and switch). Incidence and prevalence of lithium use were determined for each year between 1996 and 2005. In addition, we determined cumulative changes in lithium use (discontinuation, add-on, and switching) at three, six, 12 and 24 months for three separate time-cohorts (1998-1999, 2000-2001 and 2002-2003). Lastly, concomitant use of other drugs used in the treatment of bipolar disorders next to lithium during the 24 months after the first lithium prescription was determined for the three time-cohorts. Incidence of lithium use was constant at approximately 0.2 per 1000 person-years, prevalence increased with 26% from 0.95 to 1.2 per 1000 persons. The percentage of patients receiving an add-on drug used in the treatment of bipolar disorders was constant over the three time-cohorts, with a significant decrease in use of tricyclic antidepressants. Within the patient group that stopped using lithium, more patients switched from lithium to another agent used in the treatment of bipolar disorders over calendar time, and fewer patients discontinued lithium. There was a significant increase in the use of atypical antipsychotics and valproic acid next to lithium. We did not know the specific diagnosis for which lithium treatment was instituted. The changes were in line with the increase in alternatives during the last decade and in line with Dutch guidelines.


Malignant transformation in endometriosis of the urinary bladder.
A case of primary intravesical endometrioid carcinoma is described, together with a review of the literature. This represents the fourth reported case of malignant transformation in vesical endometriosis.


Psychological correlates of two measures of coronary-prone hostility.
The psychological correlates of the Cook and Medley Hostility (Ho) Scale and independent behavioral ratings of hostility were compared in a sample of adult, middle-aged male participants from the National Heart, Lung and Blood Institute Twin Study. Although the Ho Scale and behavioral ratings of hostility purport to measure the same construct, the underlying correlational pattern for each was quite different. Scores on the Ho Scale were associated positively with anxiety, neuroticism, and the tendency to "fake good"; behavioral hostility was related to measures of dominance, vigor, and self-confidence. Some correlates, such as the hard-driving and speed and impatience subscales from the Jenkins Activity Survey, represent a core set of correlates common to both. The meaning of hostility must be clarified before this construct's link to coronary heart disease can be defined.


Should circulatory arrest with deep hypothermia be revised in aortic arch surgery?
Our experience (January 1982-May 1987) concerns 41 patients, operated upon for aortic dissection (30 patients) or aneurysm (11 patients) using circulatory arrest with deep hypothermia. There were 24 male and 17 female patients (mean age: 55 years 9 months, range 32-73 years). The mean circulatory arrest time in minutes was 41 +/- 3 (mean rectal temperature before circulatory arrest was 18.4 degrees C +/- 0.3 degrees C). Total (24 patients) or partial (16 patients) replacement of the aortic arch was performed. One patient with a sacciform aneurysm had the aortic wall defect closed. Hospital mortality was 22% +/- 7% (9 patients): 8 of 30 patients with aortic dissection (26.6%) and 1 of 11 patients with aortic aneurysm (9%). Neurological complications occurred in 3 patients. These data lead us to prefer circulatory arrest with deep hypothermia as the method of choice for aortic arch surgery. However, when a short circulatory arrest time (less than 30 min) for the repair is foreseeable, mild hypothermia (20 degrees C-24 degrees C) may be preferred. In patients who will not tolerate excessive cardiopulmonary bypass times, expected difficulties with the repair should suggest mild hypothermia and short circulatory arrest in easier cases or moderate hypothermia with brachiocephalic perfusion in the others.


Humboldt, Darwin, and theory of evolution.
Numerous authors have examined the influence of other thinkers on Darwin's formulation of some of the key concepts of the theory of evolution. Amongst those, Alexander von Humboldt often stands out - a scholar who, following his intention to explain the interconnection of various parts of the natural system, seems to tackle the question of evolution but does not offer an explicit answer. In this article, I examine Humboldt's thoughts on evolution and the origin of species and evaluate his contribution to Darwin's theory of evolution. First, I analyse and explicate the fundamental assumptions and goals of Humboldt theory, and compare them to Darwin. Moving forward, I highlight the similarity of their methods, and argue that Humboldt and Darwin conduct similar investigation of fossil record and geographical distribution of species. Finally, I show that Humboldt acknowledges essential elements of Darwin's theory of evolution: evidence given by fossil records, struggle for survival and relation between natural environment and living organisms. Humboldt, however, concludes we cannot know the evolution of species. I explain this stance, and contend that theories of Humboldt and Darwin turn out to be more similar than they seem, yet their different conclusions regarding the evolution of species stem from different initial assumptions underlying their respective frameworks.


Decreased poststenotic flow disturbance during drag reduction by polyacrylamide infusion without increased aortic blood flow.
The infusion of polyacrylamide in open chest rats has been reported to increase aortic blood flow and the effect has been ascribed to the "drag reduction" properties of these compounds. In six anesthetized dogs the infusion of polyacrylamide to a total dose of 2 mg/kg caused a reduction in midline and separation zone Doppler spectral broadening in the common carotid artery poststenotic velocity field. This apparent reduction in poststenotic turbulence was interpreted as indicating the presence of a drag reducing effect. Despite this demonstration that polyacrylamide was present in the blood in drag reducing concentrations no increase in aortic blood flow was produced.


When coronary imaging and physiology are discordant, how best to manage coronary lesions? An appraisal of the clinical evidence.
Discordant physiology and anatomy may occur when nonsevere angiographic stenosis has positive physiology as well as the opposite situation. To underline the reasons behind the discrepancy in physiology and anatomy and to summarize the information that coronary imaging may add to physiology. A review of the published literature on physiology and intravascular imaging assessment of intermediate lesions was carried out. The limitations of angiography, the possibility of an underlying diffuse disease, the presence of a "grey zone" in both techniques, the amount of myocardial mass that subtends the stenosis, and plaque vulnerability may play a role in such discrepancy. Intracoronary imaging has a poor diagnostic accuracy compared to physiology. However, it may add information about plaque vulnerability that might be useful in deciding whether to treat or not a certain lesion. Coronary revascularization is recommended for patients with ischemia based on physiology. Intracoronary imaging adds information on plaque vulnerability and can help on the decision whether to revascularize or not a lesion.


Effect of Laser-Induced Direct Micropatterning on Polymer Optoelectronic Devices.
Solution-processed polymer devices have been studied as a low-cost alternative to the conventional vacuum-processed organic devices. However, forming a specific pattern on polymer semiconductor films without costly lithography is still challenging. Herein, we report a low-cost direct patterning method for polymer optoelectronic devices, which can successfully engrave designated patterns on the polymer semiconductor layer regardless of its size and even after device encapsulation. Irradiation of a 100 ns pulse laser forms high-resolution patterns on devices such as polymer light-emitting diodes and polymer memory devices. The biggest advantage of the proposed patterning method is that it does not produce any physical damage in the device, such as leakage current or degraded light-emitting efficiency. Analysis confirms that the laser-induced heat alters the solid or crystal structure of the polymer semiconducting layers so that the designated areas of the polymer devices can be selectively and deliberately deactivated. We demonstrate the usability of the developed laser-induced direct-patterning method on the polymer devices by engraving a digital image onto "ON-state" light-emitting devices and by generating multiple states onto a 4 × 4 matrix polymer nonvolatile memory.


Whole-Body MR Imaging: The Novel, "Intrinsically Hybrid," Approach to Metastases, Myeloma, Lymphoma, in Bones and Beyond.
Whole-body MR imaging (WB-MR imaging) has become a modality of choice for detecting bone metastases in multiple cancers, and bone marrow involvement by multiple myeloma or lymphoma. Combination of anatomic and functional sequences imparts an inherently hybrid dimension to this nonirradiating tool and extends the screening of malignancies outside the skeleton. WB-MR imaging outperforms bone scintigraphy and CT and offers an alternative to PET in many tumors by time of lesion detection and assessment of treatment response. Much work has been done to standardize procedures, optimize sequences, validate indications, confirm preliminary research into new applications, rendering clinical application more user-friendly.


Fragment-based virtual screening identifies a first-in-class preclinical drug candidate for Huntington's disease.
Currently, there are no therapies available to modify the disease progression of Huntington's disease (HD). Recent clinical trial failures of antisense oligonucleotide candidates in HD have demonstrated the need for new therapeutic approaches. Here, we developed a novel in-silico fragment scanning approach across the surface of mutant huntingtin (mHTT) polyQ and predicted four hit compounds. Two rounds of compound analoging using a strategy of testing structurally similar compounds in an affinity assay rapidly identified GLYN122. In vitro, GLYN122 directly binds and reduces mHTT and induces autophagy in neurons. In vivo, our results confirm that GLYN122 can reduce mHTT in the cortex and striatum of the R/2 mouse model of Huntington's disease and subsequently improve motor symptoms. Thus, the in-vivo pharmacology profile of GLYN122 is a potential new preclinical candidate for the treatment of HD.


Vitreous hemorrhage after trabeculotomy in aphakic eyes.
Angle surgery is often performed for pediatric glaucomas. Here we report visually significant hyphema and "spill-over" vitreous hemorrhage after trabeculotomy performed for aphakic glaucoma. Vitrectomy was necessary to remove the persistent vitreous blood in 2 of the 3 cases. We suspect this risk may be greater in aphakic eyes and propose measures to minimize this potentially amblyogenic complication.


C-reactive protein as a marker of cardiovascular disease in patients with a schizophrenia spectrum disorder treated in routine medical practice.
Interest in cardiovascular diseases (CVD) in schizophrenia has grown recently due to documented incremental mortality. C-reactive protein (CRP) has been assessed as a marker in individuals with CVD and/or at high risk of developing it. However, its role in schizophrenia patients is unknown. The goal of this research was thus to explore the use of CRP as a marker of CVD risk in patients with schizophrenia. A cross-sectional analysis of the Badalona Serveis Assistencials (BSA) administrative claims database was conducted including all subjects aged>18 years with a diagnosis of schizophrenia spectrum disorder. CRP measurement, sociodemographics, medical history, 10-year CVD risk (Framingham function) and clinical chemistry data were extracted for analysis. Seven hundred and five patients (53.0% men, 48.2 [15.8] years, 78.7% on atypicals) met criteria for analysis. Mean 10-year CVD risk was high; 11.9±5.7% and mean CRP levels were 2.6±2.5 mg/L with 30.4% showing above-normative levels (>3 mg/L). After adjusting for age, gender, smoking and presence of neoplasm or inflammatory diseases, CRP was linearly associated with 10-year CVD risk stratified by risk (low, moderate, high/very high): respectively, 2.3 (95% CI: 2.1-2.5), 3.1 (2.6-3.5) and 3.7 (3.2-4.1) mg/L; F=13.5, P<0.001. Patients with known CVD also showed higher CRP levels: 3.7 (2.9-4.5) vs. 2.5 (2.4-2.7) mg/L, P=0.008; and higher probability of above-normal values; odds ratio=4.71 (2.01-11.04), P<0.001. High CRP levels above normative were associated with both known CVD and high/very high 10-year risk of a CVD event in patients with schizophrenia, suggesting CRP could be a marker of CVD in this psychiatric disorder.


Pollen staining is a rapid and cost-effective alternative to marker-assisted selection for recessive waxy1 gene governing high amylopectin in maize.
Waxy maize is popular for food-, feed- and industrial usage. It possesses a recessive waxy1 (wx1) gene that enhances amylopectin to ~ 95-100%, compared to ~ 70-75% in traditional maize. Marker-assisted selection (MAS) is a preferred approach to converting normal maize into a waxy version. However, it requires specialized expertise, a well-equipped laboratory, and high cost. Here, pollen staining was used as an alternative approach to MAS. BC1F1, BC1F2 and BC2F2 populations in seven genetic backgrounds segregating for the wx1 gene were used. Pollens treated with iodine-potassium iodide showed that wild types (Wx1Wx1) were dark purple, while waxy pollens (wx1wx1) exhibited red colour. Heterozygotes (Wx1wx1) showed a mix of both dark purple and red colour. Staining of endosperm flour also confirmed the same findings. Wx1-based genotyping using phi022 and wx2507F/RG confirmed the same genotypic status. The average amylopectin among genotypes having red coloured pollens was 97.6%, while it was 72.5% among dark purple. Heterozygotes with both dark purple and red pollens had 85.2% amylopectin. Pollen staining showed complete agreement with the genotyping as well as amylopectin contents. Pollen staining saved 81% cost, and 54% time compared to MAS. This is the first report on the utilization of pollen staining for selecting the wx1 allele in segregating populations used for the development of waxy maize hybrids. The online version contains supplementary material available at 10.1007/s12298-022-01240-1.


Inhibition of turkey gizzard myosin light chain kinase activity by BAY K 8644.
BAY K 8644, a dihydropyridine with positive inotropic effects in smooth muscle, was found to inhibit calmodulin-dependent turkey gizzard myosin light chain kinase activity with an IC50 of 80 microM. In contrast, when myosin light chain kinase was rendered calmodulin-independent by limited proteolysis, drug inhibition was markedly diminished. BAY K 8644 inhibition was additive with that of the negative-inotropic dihydropyridine felodipine. These results indicate that the inotropic effects of dihydropyridines in smooth muscle are unrelated to their calmodulin-antagonistic properties.


Calcium diphosphatidate membrane traversal is inhibited by common phospholipids and cholesterol but not by plasmalogen.
Phosphatidate-mediated Ca2+ membrane traversal is inhibited by phospholipids (PL) such a phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin and lysoPC, but not by PC-plasmalogen. Kinetics of Ca2+ traversal through a 'passive' bilayer consisting of OH-blocked cholesterol show competition between PC and phosphatidic acid (PA); it appears likely that a Ca(PA.PC) complex is formed which is not a transmembrane ionophore but will reduce the amount of phosphatidic acid available for the formation of the ionophore, Ca(PA)2. PS and PI may inhibit Ca2+-traversal in the same manner by forming Ca(PA.PL) complexes. We suggest that PC-plasmalogen, with one of the Ca2+-chelating ester CO groups missing, cannot engage in calcium cages, i.e., Ca(PA.PL) complexes, and thus does not interfere with Ca(PA)2 formation. Double-reciprocal plotting of Ca2+ traversal rates in cholesterol-containing liposomes vs. calcium concentration suggests that cholesterol inhibits Ca2+ traversal by competing with Ca2+ for PA. The inhibition does not seem to be caused by a restructuring or dehydration of the membrane 'hydrogen belts' affected by cholesterol; most probably, it is due to hydrogen bonding of the cholesterol-OH group to a CO group of PA; this reduces the amount of PA available for the calcium ferry. The inhibition by sphingomyelin and lysoPC may also be explained by their OH group interacting with PA via hydrogen bonding. The pH dependence of Ca2+ traversal suggests that H[Ca(PA)2]- can serve as Ca2+ cross-membrane ferry but that at physiological pH, [Ca(PA)2]2- is the predominant ionophore. In conclusion, the results indicate that Ca2+ traversal is strongly dependent on the structure of the hydrogen belts, i.e., the membrane strata occupied by hydrogen bond acceptors (CO of phospholipids) and donors (OH of cholesterol, sphingosine), and that lipid hydrogen belt structures may regulate storage and passage of Ca2+.


Recurrent eczema herpeticum - a retrospective European multicenter study evaluating the clinical characteristics of eczema herpeticum cases in atopic dermatitis patients.
Eczema herpeticum (EH) is a disseminated viral infection of eczematous skin disease with the herpes simplex virus. Knowledge on clinical characteristics, risk factors and recurrent disease is limited. Our aim was to better define clinical characteristics and risk factors for EH and especially for recurrent EH. A retrospective analysis of EH cases assessed the history, clinical signs, prior treatment and laboratory results using a predefined questionnaire. A total of 224 EH cases from eight European centres were included. Extrinsic AD was identified as risk factor for EH, and only one patient suffered from intrinsic AD. Early onset of AD was identified as risk factor for recurrent EH. Pretreatment with topical steroids, systemic steroids, topical calcineurin inhibitors or plain emollients reflected standard therapy. Many patients showed AD lesions without EH, but skin without AD lesions was never affected by herpetic lesions. Patients with clinically active, extrinsic AD are at risk of EH. Recurrent EH is associated with confounders of severe atopic distortion and requires active AD lesions for clinical manifestation. Recurrent eczema herpeticum mainly affects patients with early onset of AD.


Electrophysiological properties of neurons in neonatal rat occipital cortex slices grown in a serum-free medium.
The electrophysiological properties of individual neurons within organotypic explants of neonatal rat cortex were examined via intracellular recordings. The explants were grown for two weeks in a serum-free medium. The electrophysiological properties of the neurons within these explants were similar to those reported for both adult cortex in vivo and short-term in vitro slice preparations. The results of the present study show that cortical explants grown under serum-free conditions can serve as a useful model for long-term developmental studies associated with the physiological basis of neural network formation.


The association of alcohol consumption with metabolic syndrome and its individual components: the Taichung community health study.
Alcohol has both adverse and protective effects on the individual components of metabolic syndrome (MS). We hypothesize that alcohol consumption increases the risk of developing MS and that the consumption of different types of alcoholic beverages has different effects on the development of MS and its individual components. We enrolled 2358 men for this cross-sectional study. The data were collected from self-reported nutrition and lifestyle questionnaires. Individuals who drank at least once per week for 6 consecutive months were classified as current drinkers. Current drinkers were at a higher risk of developing MS, abdominal obesity, and high triglyceride levels, but they were at a lower risk of developing low levels of high-density lipoprotein cholesterol (HDL-C). The increased risk of developing MS, high triglyceride, and high fasting glucose levels was dose dependent, whereas low HDL-C levels demonstrated a reverse relationship. The dose needed to reduce the risk of having low HDL-C levels was ≧50 g/d. This dose, however, resulted in an increased risk of developing high fasting glucose and high triglyceride levels. Consuming mixed types of alcohol increased the risk of developing MS and abdominal obesity. Meanwhile, those who drank liquor or wine had a greater risk of developing high triglyceride or high fasting glucose levels, respectively. In conclusion, alcohol consumption dose-dependently increased the risk of developing MS and some of its individual components while dose-dependently decreasing the risk of developing low HDL-C levels. The type of alcoholic beverage had different effects on the development of the individual components of MS.


Toxic effects of natural saline waters on mallard ducklings.
Water from 10 saline wetlands in Saskatchewan was provided as drinking water for 1-day-old mallards (Anas platyrhynchos). Ducklings given water with conductivity from 3,750 to 7,490 microns hos/cm grew as well as birds on fresh water during a 14-day trial, but birds given water with conductivity of 4,000 microns hos/cm grew poorly during the last 2 wk of a 28-day trial. Ducklings given water with conductivity of 7,720 micron hos/cm grew poorly during a 14-day trial. Six of 10 ducklings given water with conductivity of 20,000 microns hos/cm died, and only two of nine ducklings given water with conductivity of 21,500 microns hos/cm survived 14 days. Survivors were much smaller than controls and had many abnormalities. All ducklings given water with conductivity of 35,000 and 67,000 microns hos/cm died within 60 and 30 hr, respectively. The results indicate that ducklings hatched on many saline wetlands will suffer toxic effects unless they are able to find a source of fresh water shortly after hatching.


Detection of a novel HLA-A*30 variant, A*30:109, in a Taiwanese individual.
One nucleotide substitution at residue 488 of HLA-A*30:01:02 results in a novel allele, HLA-A*30:109.


Tetra-aqua-bis-[4-(4H-1,2,4-triazol-4-yl)benzoato-κN]nickel(II) deca-hydrate.
In the title compound, [Ni(C(9)H(6)N(3)O(2))(2)(H(2)O)(4)]·10H(2)O, the Ni(II) ion lies on a twofold rotation axis and displays a slightly distorted octa-hedral geometry defined by two N atoms from two monodentate 4-(1,2,4-triazol-4-yl)benzoate ligands and four water mol-ecules, two of which also lie on the twofold rotation axis. In the crystal, the complex mol-ecules and uncoordinated water mol-ecules are linked via inter-molecular O-H⋯N and O-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular network. π-π inter-actions between the benzene rings provide additional stability of the crystal packing [centroid-centroid distance = 3.792 (2) Å].


Testicular Tissue Cryopreservation and Ethical Considerations: A Scoping Review.
Testicular tissue cryopreservation (TTCP) aims to preserve the future option of genetic reproduction for prepubescent cancer patients who are at risk of infertility as a result of their cancer therapies. This technology is experimental and currently only offered in the research context. As TTCP moves towards becoming more widely available, it is imperative that healthcare providers recognize the complex ethical issues surrounding this technology. This scoping review study identifies and assesses the range and depth of ethical concerns related to this testicular tissue cryopreservation technology. At present, no such scoping review of ethical concerns exists in the TTCP literature. The forty-three full-text articles included in this study yielded twenty-two different ethical considerations discussed in relation to TTCP. It was observed that these ethical considerations fit within a mainstream Principlism approach to bioethics. Accordingly, there are ethical gaps in the TTCP literature that can be identified with alternative moral lenses. In particular, it was found that ethical concerns related to context and relational aspects of identity were absent in nearly all ethical examinations of TTCP. Furthermore, only 9 per cent of articles reviewed in this study focused primarily on the ethics of TTCP, thus demonstrating a need for further in depth ethical analyses of this technology. The results of this study are important for supporting the ethical provision of TTCP and can contribute to policy and guideline development. The findings of this study demonstrate the need for greater depth and diversity in analyses of ethical considerations related to this technology.


Correction: Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy.
[This corrects the article DOI: 10.1371/journal.pntd.0004600.].


WITHDRAWN BY THE AUTHORS: Molecular mechanism of extracellular nucleotide-induced degranulation from human polymorphonuclear leukocytes: Role of leukotriene B4 and p38 MAP kinase as essential intermediates.
WITHDRAWN BY THE AUTHORS.


Shedding light on the electron transfer chain of a moderately acidophilic iron oxidizer: characterization of recombinant HiPIP-41, CytC-18 and CytC-78 derived from Ferrovum sp. PN-J47-F6.
Efficient electron transfer from the donor to the acceptor couple presents a necessary requirement for acidophilic and neutrophilic iron oxidizers due to the low energy yield of aerobic ferrous iron oxidation. Involved periplasmic electron carriers are very diverse in these bacteria and show adaptations to the respective thermodynamic constraints such as a more positive redox potential reported for extreme acidophilic Acidithiobacillus spp. Respiratory chain candidates of moderately acidophilic members of the genus Ferrovum share similarities with both their neutrophilic iron oxidizing relatives and the more distantly related Acidithiobacillus spp. We examined our previous omics-based conclusions on the potential electron transfer chain in Ferrovum spp. by characterizing the three redox protein candidates CytC-18, CytC-78 and HiPIP-41 of strain PN-J47-F6 which were produced as recombinant proteins in Eschericha coli. UV/Vis-based redox assays suggested that HiPIP-41 has a very positive redox potential while redox potentials of CytC-18 and CytC-78 are more negative than their counterparts in Acidithiobacillus spp. Far Western dot blotting demonstrated interactions between all three recombinant redox proteins while redox assays showed the electron transfer from HiPIP-41 to either of the cytochromes. Altogether, CytC-18, CytC-78 and HiPIP-41 indeed represent very likely candidates of the electron transfer in Ferrovum sp. PN-J4-F6.


[On the issue of separate designation of the pre-Descemet's layer in the structure of the cornea].
In 2013, based on the results of an experimental pneumodissection of the cornea, English ophthalmologist H. Dua postulated the existence of a previously unknown pre-Descemet's layer (PDL) with unique characteristics. However, the need to revise the traditional concepts of the corneal structure raises reasonable doubts among many researchers. This article discusses the question of whether the structural features of the pre-Descemet's layer can be a sufficient basis for designating it as a separate anatomical unit.


Management of tachyarrhythmias with dual-chamber pacemakers.
Multiprogrammable dual-demand AV sequential (DVI, MN) pacemakers were implanted in twenty-three patients (in one of them a DVI, MN unit was used as a VVI, MN with the aid of an atrial plug) with supraventricular tachycardias after electrophysiological studies revealed a great variety of AV reentry circuits. The latter included tachycardias involving accessory pathways of the Kent type, manifest or concealed Wolff-Parkinson-White syndromes, nodo-ventricular (Mahaim) tracts, "enhanced" AV node (or extra AV nodal) pathways and dual AV pathways. In addition, multiprogrammable "non-committed" AV sequential (DVI, MN and DDD, M) pacemakers were permanently implanted to treat different forms of ventricular tachyarrhythmias that included: torsade de pointes in the Romano-Ward syndrome and Chagas' cardiomyopathy, ventricular tachycardia which is bradycardia-dependent (in Chagas' cardiomyopathy) and reciprocal beats induced by, and producing severe hemodynamic derangements in a patient with a conventional VVI unit. With small-size multiprogrammable units, arrhythmias may be treated by changing parameters non-invasively. By temporary inhibition, one may analyze the underlying rhythm and pacemaker dependency. In patients without chronic atrial flutter/fibrillation who require pacing and possibly tachyarrhythmia control, our experience with multiprogrammable "non-committed" AV sequential pacing has been very satisfactory. The evolution toward newer pacing modes which provide atrial sensing and tracking (DDD), and thus preserve AV synchrony over a wider range of atrial rates, may contribute even further to successful patient management. This may be applicable to pediatric patients as well.


[Muscular atrophy associated with a contralateral parietal lobe lesions. Apropos of 2 cases].
Two cases of parietal lobe tumours with contralateral muscle atrophy are discussed. Muscle biopsy demonstrated selective atrophy of Type II fibres. E.M.G. shows brief small polyphasic potentials. At autopsy in the second case no neurological lesion was found outside the brain, muscles and pyramidal tract.


Knowledge, Attitude, and Practice of Breast Cancer Patients Toward Lymphedema Complications: Cross-Sectional Study.
Breast cancer is commonly treated through surgical resection, but a common complication of the procedure is lymphedema of the upper limbs, which can significantly impact patients' daily life. This study aims to investigate the knowledge, attitude, and practice (KAP) of breast cancer patients with regard to lymphedema complications. This cross-sectional study was conducted by a self-administered questionnaire between August and October 2022 toward breast cancer patients in our Hospital of Traditional Chinese Medicine. A total of 529 breast cancer patients were enrolled, including 186 (35.16%) aged < 50 years old. Participants had moderate knowledge, attitudes, and practices with scores of 18.24 ± 3.145 (possible range: 0-30), 62.24 ± 10.260 (possible range: 17-85), and 63.27 ± 20.967 (possible range: 21-105), respectively. Multivariate logistic regression showed that high school/technical secondary school (OR = 1.880, 95% CI = 1.107-3.194, P = 0.019) and being retired (OR = 0.482, 95% CI = 0.245-0.947, P = 0.034) were independently associated with good knowledge. Knowledge (OR = 1.321, 95% CI = 1.222-1.428, P < 0.001) was independently associated with a good attitude. Furthermore, knowledge (OR = 1.262, 95% CI = 1.151-1.384, P < 0.001) and attitude (OR = 1.122, 95% CI = 1.085-1.160, P < 0.001) were independently associated with good practice. Breast cancer patients have moderate knowledge, attitudes, and practices regarding lymphedema complications. Effective education and self-management programs are needed to improve patients' KAP toward lymphedema.


Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia.
The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.


Survey of the exocrine system in Protanilla wallacei (Hymenoptera, Formicidae).
We studied the exocrine system of both workers and ergatoid queens of Protanilla wallacei using light, scanning and transmission electron microscopy. Our survey revealed the presence of 26 glands, of which 6 had never been found before in ants. Five of these represent novel discoveries for social insects in general. The overall novel discoveries comprise an epithelial stipes gland, a pharyngeal wall gland, a central petiole gland, a lateral postpetiole gland and a foot-sole gland in the hindleg pretarsi. The intramandibular epithelial gland was already reported in some bees previously, but is now for the first time also reported in ants. The exocrine system of workers and ergatoid queens is very similar, with only the spermathecal gland showing an obvious difference. This is in line with the limited anatomical as well as behavioural difference between both castes in Protanilla compared to the situation in Leptanilla.


Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature.
Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases, including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with systemic adverse events and devastating ocular complications. In this review, we provide an overview of safety data for intravitreal injection of common anti-VEGF agents.


The effect of natural clinoptilolite on the serotonergic receptors in the brain of mice with mammary carcinoma.
The ex vivo effect of tribomechanically micronized zeolite (MZ) on the binding of 3H-8-OH-DPAT to 5-HT(1A) and 3H-5-HT to 5-HT(1B) receptors was investigated in the brain of nontumorous (control) and mammary carcinoma bearing female mice. During 14 and 28 days mice were fed with standard food, standard food supplemented with 25% of MZ, or standard food supplemented with 25% of non tribomechanically micronized zeolite (non-MZ). A reduced binding of 3H-8-OH-DPAT to 5-HT(1A) receptors in mammary carcinoma bearing mice was found when compared to control mice fed with standard food for 28 days, suggesting a time dependent alteration of 5-HT(1A) receptors in mammary carcinoma. The addition of MZ for 28 days in these mice abolished the decrease in 5-HT(1A) receptors binding, indicating a possible beneficial effect of MZ, at least on 5-HT(1A) receptors in mammary carcinoma bearing mice. The preliminary data show that MZ administered as a food supplement (25%) for 14 days induced a transient decrease in the binding of 3H-5-HT to brain 5-HT(1B) receptors only in control, but not in tumor-bearing mice, that disappeared after 28 days of MZ-supplemented food administration. The mechanism of the indirect action of MZ on the brain serotonergic receptors might be achieved by the alterations in the electrolytes balance, and/or by the regulation of the immune system.


An overview of the intracranial vault. Physiology and philosophy.
This overview of the intracranial vault from a physiologic and philosophic basis should set the stage for a critical analysis of the contents of this volume. There is much to be taught in this area but even more to be learned.


Long-term effect of insulin treatment in cystic fibrosis-related diabetes.
Although insulin treatment confers short-term benefit in cystic fibrosis-related diabetes (CFRD), few studies have compared its long-term effect on the clinical outcome. In this study, we aimed to investigate the long-term impact of insulin treatment on pulmonary function, nutritional status and hospital admissions in patients with CFRD. We reviewed pulmonary function, body mass index (BMI) and hospital admissions 5 years before and 3 years after insulin therapy in 42 adult CFRD patients. Prior to treatment, over a period of 5 years, the annual rate of change in forced expiratory volume in 1 s (FEV(1)) was -3.2%, forced vital capacity (FVC) -2.5%, and BMI -0.07%. At treatment of CFRD (baseline), the mean FEV(1) was 51.6% predicted (range 24-96), FVC 66.4% (range 29-103) and BMI 19.5 (range 15.3-29.5). At 3 months following insulin treatment, there was a significant improvement in all parameters, which was maintained at 1 year for FEV(1) (55.1%; p < 0.002), 2 years for FVC (72.1%; p < 0.01) and at 3 years for BMI (20.4%; p < 0.002). After 3 months, FEV(1) declined at a rate similar to that before treatment (-3.2 vs. -3.1% per year; p = 0.77), such that the mean FEV(1) after treatment returned to pretreatment baseline values at 34 months. There was no difference in the number of hospital admissions with insulin treatment. Insulin enhances the nutritional state and temporarily improves pulmonary function in CFRD patients, on average delaying the decline in FEV(1) by 34 months.


Tumoricidal activity of high-dose tumor necrosis factor-alpha is mediated by macrophage-derived nitric oxide burst and permanent blood flow shutdown.
This study investigates the role of tumor nitric oxide (NO) and vascular regulation in tumor ulceration following high-dose tumor necrosis factor-alpha (TNF) treatment. Using TNF-responsive (MethA) and nonresponsive (LL2) mouse tumors, tumor NO concentration was measured with an electrochemical sensor and tumor blood flow by Doppler ultrasound. Mice were also pretreated with a selective inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. Tumors harvested from TNF-treated mice were cryosectioned and immunostained for murine macrophages, or/and iNOS. MethA tumor-bearing mice were depleted of macrophages. Pre- and post-TNF tumor NO levels were measured continuously, and mice were followed for gross tumor response. In MethA tumors, TNF caused a 96% response rate, and tumor NO concentration doubled. Tumor blood flow decreased to 3% of baseline by 4 hr and was sustained at 24 hr and 10 days post-TNF. Selective NO inhibition with 1400 W blocked NO rise and decreased response rate to 38%. MethA tumors showed tumor infiltration by macrophages post-TNF and the pattern of macrophage immunostaining overlapped with iNOS immunostaining. Depletion of macrophages inhibited tumor NO increase and response to TNF. LL2 tumors had a 0% response rate to TNF and exhibited no change in NO concentration. Blood flow decreased to 2% of baseline by 4 hr, recovered to 56% by 24 hr and increased to 232% by 10 days. LL2 tumors showed no infiltration by macrophages post-TNF. We conclude that TNF causes tumor infiltrating, macrophage-derived iNOS-mediated tumor NO rise and sustained tumor blood flow shutdown, resulting in tumor ulceration in the responsive tumor.


Parallel two-photon lithography achieving uniform sub-200 nm features with thousands of individually controlled foci.
The limited throughput of nano-scale laser lithography has been the bottleneck for its industrial applications. Although using multiple laser foci to parallelize the lithography process is an effective and straightforward strategy to improve rate, most conventional multi-focus methods are plagued by non-uniform laser intensity distribution due to the lack of individual control for each focus, which greatly hinders the nano-scale precision. In this paper, we present a highly uniform parallel two-photon lithography method based on a digital mirror device (DMD) and microlens array (MLA), which allows the generation of thousands of femtosecond (fs) laser foci with individual on-off switching and intensity-tuning capability. In the experiments, we generated a 1,600-laser focus array for parallel fabrication. Notably, the intensity uniformity of the focus array reached 97.7%, where the intensity-tuning precision for each focus reached 0.83%. A uniform dot array structure was fabricated to demonstrate parallel fabrication of sub-diffraction limit features, i.e., below 1/4 λ or 200 nm. The multi-focus lithography method has the potential of realizing rapid fabrication of sub-diffraction, arbitrarily complex, and large-scale 3D structures with three orders of magnitude higher fabrication rate.


Convergence of virulence and resistance in international clones of WHO critical priority enterobacterales isolated from Marine Bivalves.
The global spread of critical-priority antimicrobial-resistant Enterobacterales by food is a public health problem. Wild-caught seafood are broadly consumed worldwide, but exposure to land-based pollution can favor their contamination by clinically relevant antimicrobial-resistant bacteria. As part of the Grand Challenges Explorations: New Approaches to Characterize the Global Burden of Antimicrobial Resistance Program, we performed genomic surveillance and cell culture-based virulence investigation of WHO critical priority Enterobacterales isolated from marine bivalves collected in the Atlantic Coast of South America. Broad-spectrum cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli isolates were recovered from eight distinct geographical locations. These strains harbored blaCTX-M-type or blaCMY-type genes. Most of the surveyed genomes confirmed the convergence of wide virulome and resistome (i.e., antimicrobials, heavy metals, biocides, and pesticides resistance). We identified strains belonging to the international high-risk clones K. pneumoniae ST307 and E. coli ST131 carrying important virulence genes, whereas in vitro experiments confirmed the high virulence potential of these strains. Thermolabile and thermostable toxins were identified in some strains, and all of them were biofilm producers. These data point to an alarming presence of resistance and virulence genes in marine environments, which may favor horizontal gene transfer and the spread of these traits to other bacterial species.


Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in surface waters, sediments, soils and wastewater - A review on concentrations and distribution coefficients.
The sorption of perfluorinated compounds (PFCs) to soils and sediments determines their fate and distribution in the environment, but there is little consensus regarding distribution coefficients that should be used for assessing the environmental fate of these compounds. Here we reviewed sorption coefficients for PFCs derived from laboratory experiments and compared these values with the gross distribution between the concentrations of PFCs in surface waters and sediments or between wastewater and sewage sludge. Sorption experiments with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) suggest that their sorption can be described reasonably well as a partitioning-like process with an average log K(oc) of approximately 2.8 for PFOA and 3.0 for PFOS. However, median concentrations in sediments (PFOA, 0.27 ng g(-1); PFOS, 0.54 ng g(-1)) or sewage sludge (PFOA, 37 ng g(-1); PFOS, 69 ng g(-1)) in relation to median concentrations in surface water (PFOA, 3ngl(-1); PFOS, 3ngl(-1)) or wastewater treatment effluent (PFOA, 24 ng l(-1); PFOS, 11 ng l(-1)), suggest that effective log K(oc) distribution coefficients for the field situation may be close to 3.7 for PFOA and 4.2 for PFOS. Applying lab-based log K(oc) distribution coefficients can therefore result in a serious overestimation of PFC concentrations in water and in turn to an underestimation of the residence time of PFOA and PFOS in contaminated soils. Irrespective of the dissipation kinetics, the majority of PFOA and PFOS from contaminated soils will be transported to groundwater and surface water bodies.