The histological course of reactions in borderline leprosy and their outcome.
The histological course and the outcome of reactions was followed in 12 patients who were all in the borderline (BT-BL) zone of the spectrum at some time during the reaction. In eight patients the reaction proved to be of the upgrading or reversal type with a shift in classification toward the tuberculoid pole. In two patients the reaction was of the opposite downgrading type, and in two there was no significant change in classification as a result of the reaction. Early reactions were characterized by edema and an increase in the number of lymphocytes which was more marked in upgrading than downgrading reactions, but at this stage the outcome could not be reliably predicted. In the acute stage necrosis was apparent in severe cases and was followed by giant cell formation and the evolution of the granuloma cells depending on the direction of the shift: organized clusters of mature epithelioid cells in upgrading, macrophages in downgrading. At all stages the collagen of the dermis might be involved in varying degree, which in extreme cases included fibrinoid necrosis and scarring in the late stage. The histology is compared to that of tuberculin reactions. All cases were bacteriologically positive at the onset of the reaction. The results were consistent with the view that these reactions are delayed type hypersensitivity phenomena associated with the unmasking of bacterial antigen in nerve or other protected sites, or with an increase of hypersensitivity as a result of treatment. They demonstrate the evolution of a granuloma in mycobacterial disease.


Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer's disease.
Alzheimer's disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation of cell type-specific responses and cellular heterogeneity in AD is required to provide precise molecular and cellular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis of 169,496 nuclei from the prefrontal cortical samples of AD patients and normal control (NC) subjects. Differential analysis shows that the cell type-specific transcriptomic changes in AD are associated with the disruption of biological processes including angiogenesis, immune activation, synaptic signaling, and myelination. Subcluster analysis reveals that compared to NC brains, AD brains contain fewer neuroprotective astrocytes and oligodendrocytes. Importantly, our findings show that a subpopulation of angiogenic endothelial cells is induced in the brain in patients with AD. These angiogenic endothelial cells exhibit increased expression of angiogenic growth factors and their receptors (i.e., EGFL7, FLT1, and VWF) and antigen-presentation machinery (i.e., B2M and HLA-E). This suggests that these endothelial cells contribute to angiogenesis and immune response in AD pathogenesis. Thus, our comprehensive molecular profiling of brain samples from patients with AD reveals previously unknown molecular changes as well as cellular targets that potentially underlie the functional dysregulation of endothelial cells, astrocytes, and oligodendrocytes in AD, providing important insights for therapeutic development.


Delirium During Critical Illness and Subsequent Change of Treatment in Patients With Cancer: A Mediation Analysis.
To assess whether delirium during ICU stay is associated with subsequent change in treatment of cancer after discharge. Retrospective cohort study. A 50-bed ICU in a dedicated cancer center. Patients greater than or equal to 18 years old with a previous proposal of cancer treatment (chemotherapy, target therapy, hormone therapy, immunotherapy, radiotherapy, oncologic surgery, and bone marrow transplantation). None. We considered delirium present if Confusion Assessment Method for the ICU was positive. We assessed the association between delirium and modification of the treatment after discharge. We also performed a mediation analysis to assess both the direct and indirect (i.e., mediated by the development of functional dependence after discharge) of delirium on modification of cancer treatment and whether the modification of cancer treatment was associated with mortality at 1 year. We included 1,134 patients, of whom, 189 (16.7%) had delirium. Delirium was associated with the change in cancer treatment (adjusted odds ratio [OR], 3.80; 95% CI, 2.72-5.35). The association between delirium in ICU and change of treatment was both direct and mediated by the development of functional dependence after discharge. The proportion of the total effect of delirium on change of treatment mediated by the development of functional dependence after discharge was 33.0% (95% CI, 21.7-46.0%). Change in treatment was associated with increased mortality at 1 year (adjusted OR, 2.68; 95% CI, 2.01-3.60). Patients who had delirium during ICU stay had a higher rate of modification of cancer treatment after discharge. The effect of delirium on change in cancer treatment was only partially mediated by the development of functional dependence after discharge. Change in cancer treatment was associated with increased 1-year mortality.


Association of strategic management with vaccination in the terms of globalization.
Globalization is having an ever growing impact on the field of vaccine production and distribution in the world and domestically. In this article we examine the impact of taking a strategic approach to vaccination programmes by all the relevant actors: WHO, UNICEF, national immunization programmes, and vaccine manufacturers and distributors. The review of the relevant literature indicates that there are commonalities to the worldwide vaccination programmes. A comparative analysis of various vaccination strategies recommended by WHO and the immunization calendars of certain European countriesis made as well as an analysis of the Serbian vaccination programme. New and more expensive vaccines will continue to appear on the market in increasingly short periods of time.


A dose escalation study of total body irradiation followed by high-dose etoposide and allogeneic blood stem cell transplantation for the treatment of advanced hematologic malignancies.
Since approximately 30% of leukemia patients relapse after allogeneic BMT using total body irradiation (TBI)-based preparative regimens, treatment intensity may be suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. We studied the feasibility and toxicity of escalating the doses of fractionated TBI above our previous prescription of 13.5 Gy. Sixteen evaluable patients with advanced hematologic malignancies were treated with twice daily TBI using a high-energy source (18-24 MV). The first patient cohort (n = 11) received a total dose of 14.4 Gy in nine fractions, and the second cohort (n = 5) received doses escalated to 15.3 Gy. All patients received high-dose etoposide (60 mg/kg) and allogeneic stem cell transplantation following the TBI. All patients had HLA-identical sibling donors. The median times for neutrophil and platelet engraftment were 13.5 and 12 days, respectively, and did not differ between the two cohorts. All but one patient developed treatment-related grade 3 or 4 mucositis. There were three cases of grade 4 pulmonary toxicity and three cases of grade 4 hepatic toxicity among the 14.4 Gy cohort, and one case each of grade 4 pulmonary and hepatic toxicities among the 15.3 Gy cohort. In most cases comorbid conditions contributed to these toxicities. Two patients had significant GVHD of the GI tract. Six relapses occurred, five (45%) in the 14.4 Gy cohort and one (20%) in the 15.3 Gy cohort. The 100-day treatment-related mortality rates were 9% and 20% for the 14.4 Gy and 15.3 Gy cohorts, respectively, and the median survivals were 226 and 201 days, respectively. We conclude that TBI dose escalation above the previously used 13.5 Gy dose is feasible using a high-energy source and high-dose etoposide. Acute and chronic toxicities were primarily related to GVHD, infection and relapse rather than to TBI.


Development of discriminant functions to estimate sex in upper limb bones for mixed ancestry South Africans.
South Africa has one of the highest murder rates in the world, which is associated with an increasing number of unidentified individuals. Forensic anthropologists can assist in these cases to reduce the number of potential victims the remains may belong to. Sex estimation potentially decreases the number of possible victims by half. The mixed ancestry population in South Africa is the second largest group of people; however, there remains a paucity of data and population-specific methods for sex estimation in this group. The aim of this study was to assess the potential for metrices obtained around the nutrient foramen and the maximum length of upper limb long bones to estimate sex in mixed ancestry South Africans using discriminant function analysis. A total of 328 humeri, radii and ulnae from individuals of mixed ancestry were analysed. Sex was correctly classified with an average classification accuracy of 84.3% in the humeri, 88.3% for radii and 83.5% for the ulnae. Total length was the single best predictor of sex; the combination of total length with dimensions related to the nutrient foramen produced high classification accuracies in the current study. Overall, sexual dimorphism was observed in mixed ancestry South Africans upper limb long bones. The findings of this study further emphasise the need for population-specific standards of sexing in an attempt to improve current methods of forensic identification of descendants.


Maintenance of interphase chromosome compaction and homolog pairing in Drosophila is regulated by the condensin cap-h2 and its partner Mrg15.
Dynamic regulation of chromosome structure and organization is critical for fundamental cellular processes such as gene expression and chromosome segregation. Condensins are conserved chromosome-associated proteins that regulate a variety of chromosome dynamics, including axial shortening, lateral compaction, and homolog pairing. However, how the in vivo activities of condensins are regulated and how functional interactors target condensins to chromatin are not well understood. To better understand how Drosophila melanogaster condensin is regulated, we performed a yeast two-hybrid screen and identified the chromo-barrel domain protein Mrg15 to interact with the Cap-H2 condensin subunit. Genetic interactions demonstrate that Mrg15 function is required for Cap-H2-mediated unpairing of polytene chromosomes in ovarian nurse cells and salivary gland cells. In diploid tissues, transvection assays demonstrate that Mrg15 inhibits transvection at Ubx and cooperates with Cap-H2 to antagonize transvection at yellow. In cultured cells, we show that levels of chromatin-bound Cap-H2 protein are partially dependent on Mrg15 and that Cap-H2-mediated homolog unpairing is suppressed by RNA interference depletion of Mrg15. Thus, maintenance of interphase chromosome compaction and homolog pairing status requires both Mrg15 and Cap-H2. We propose a model where the Mrg15 and Cap-H2 protein-protein interaction may serve to recruit Cap-H2 to chromatin and facilitates compaction of interphase chromatin.


Host Population Expansion and the Genetic Architecture of the Pinniped Hookworm Uncinaria lucasi.
The long-term fidelity of pinniped hosts to their natal rookery site suggests the genetic architecture of their Uncinaria spp. hookworms should be strongly structured by host breeding biology. However, historical events affecting host populations may also shape parasite genetic structure. Sequences of the mitochondrial cytochrome c oxidase 1 (COI) gene of 86 Uncinaria lucasi individuals were obtained to assess genetic variation and structure of nematodes from 2 host species (68 hookworms from northern fur seals; 18 hookworms from Steller sea lions) and rookeries from 3 widely separated geographic regions: the western Bering Sea and Sea of Okhotsk, eastern Bering Sea, and the eastern Pacific Ocean. High COI haplotype (h = 0.96-0.98) and nucleotide (π = 0.014) diversity was found. The haplotype network showed a star-shaped pattern with a large number of haplotypes separated by few substitutions. The network did not show separation of U. lucasi by geographic region or host species. Fst values between U. lucasi individuals representing geographic regions showed no differentiation, consistent with the absence of genetic structure. At face value, this lack of genetic structure in U. lucasi suggests high gene flow but could also be explained by recent (post-glacial) population expansions of northern fur seals and their hookworms.


Catastrophic cardiovascular consequences of weight lifting in a family with Marfan syndrome.
Marfan syndrome primarily involves the musculoskeletal, cardiovascular, and ocular systems. Isometric exercises such as weight lifting lead to significant stress along the aortic wall and predispose patients to dissection and rupture. A 30-year-old male patient presented with a complaint of back pain. He had a history of two operations for recurrent inguinal hernia. His father and elder brother died on separate occasions following loss of consciousness after weight lifting. He also had a brother who had undergone an emergency operation for De Bakey type I acute aortic dissection after presentation with acute back pain following weight lifting. The patient was 180 cm tall, had elongated limbs and arachnodactyly. On auscultation, there was a diastolic murmur of 1-2/6 over the aortic area. A chest roentgenogram demonstrated mild cardiomegaly and mediastinal widening. Transthoracic echocardiography showed moderate aortic insufficiency with dilatation of the aortic root and ascending aorta. He was diagnosed as having Marfan syndrome and underwent complete replacement with a composite aortic valve-ascending aortic conduit. Histologic sections of the ascending aortic wall showed medial cystic and myxoid degeneration and loss of nuclei in the media. Von Gieson staining showed elastic fragmentation and loss of elastic lamellae. Screening of other family members showed Marfan syndrome in his sister and in one of his nephews. His other two brothers had Marfanoid habitus without findings of systemic involvement.


Analysis of isoproterenol-induced changes in gastrocnemius muscle and serum lactate dehydrogenase expression in mice.
Beta-adrenergic agonists are highly abused by sportspeople for their muscle anabolic and lipolytic effects. Muscle growth effects are thought to result from beta-2 adrenoceptor activation. This study attempted to characterise muscle (gastrocnemius) tissue damage following the administration of isoproterenol. Adult male Balb-C mice were treated with a single oral dose of isoproterenol (100 mg/kg body weight) for 4, 8, 20, 48 and 72 hours. Control mice received equal doses of saline. The animals were killed at the respective stages, followed by the collection of gastrocnemius and blood. Serum was then separated from blood. Histopathology and lactate dehydrogenase (LDH) assays were performed. Beta-adrenoceptor activation-induced histological changes began with structural aberrations, and ultimately resulted in myonecrosis and extensive degeneration within hours of the administration of isoproterenol. The effects of beta-agonist administration on muscle myofibre organisation were visible within four hours and became most prominent at 20 and 48 hours. Augmentation of more than 20 percent in muscle LDH activity was observed at 4, 8 and 72 hour stages, and was accompanied by a significant decline of 19 and 27 percent at 20 and 48 hour time points, respectively. Serum corroborated the above results. Isoproterenol treatment produced considerable histopathological changes, including myonecrosis in mice gastrocnemius, resulting in a leaky sarcolemma and the release of marker enzyme, LDH into the serum (more evident after 20 and 48 hours). This suggests that isoproterenol promotes the process of necrosis in mice gastrocnemius at the concentration employed, which raises a significant question regarding the use and abuse of beta-agonists.


Nuclear magnetic resonance imaging of the vitreous body.
Imaging with proton nuclear magnetic resonance is a valuable new tool for studying the vitreous body of the eye. It is particularly suited for the detection of vitreal liquefaction and intraocular hemorrhage because of the dependence of the signal on the physical environment of water. Conversely, the vitreous body provides a new model for studying changes in proton relaxation times of protein solutions in biological systems.


Low repetitive DNA content in Aspergillus nidulans.
DNA-DNA reassociation experiments show that the genome of Aspergillus nidulans consists of approximately 97 to 98 percent unique and 2 to 3 percent reiterated sequences. The reiterated DNA sequences have a complexity of about 11,000 base pairs and are repeated approximately 60 times per haploid genome. Ribosomal RNA-DNA hybridization experiments indicate that most of the repetitive DNA codes for ribosomal RNA.


A radiological study of 3M Capital femoral hip prostheses: an analysis of factors predisposing to failure.
We conducted a radiographic assessment of 180 flanged modular titanium alloy Capital femoral hip replacements. Six significant factors associated with failure are identified. The mean follow-up period was 7.9 years (2.1-16 years) and there were 26 (14%) radiographic failures irrespective of whether these were symptomatic or led to revision. Failure, if it is going to occur, is initiated early, within an average of 1.4 years, and becomes clinically evident very quickly; the remainder appear to sustain more likelihood of stable survival. This is the longest published follow-up and it suggests that the survival is better than indicated in some other series. If the identified prejudicial aspects of surgical technique had not been present, it follows that the results would have been better. Comparison with other published series is attempted.


A pseudoduplication in Lycopersicon pimpinellifolium.
A double-banded variant of Prx-2 encountered in a single wild plant in a previous survey of the peroxidases of Lycopersicon pimpinellifolium was subjected to genetic analysis. Segregations obtained from crosses of this true-breeding type with various alleles of Prx-2 yielded anomalous segregations that are not compatible with a single locus model and suggest activity of alleles of a gene at another, independent locus. A critical test was afforded by studying simultaneous segregation for the apparent duplication and for two alleles at the neighboring Prx-3, a gene which proves to be very tightly linked with Prx-2. The results of the new test revealed independence between the double-banded type and Prx-3, hence also between the former and Prx-2. The most tenable hypothesis stipulates that an independent gene mPx2(1) modifies post-translationally the product coded by Prx-2(+) to yield two electrophoretically separable isozymes. These results reveal the risk of assuming, without appropriate genetic tests, that gene duplication is necessarily the cause of multiple banding.


Retinal macroaneurysm: natural history and guidelines for treatment.
This report describes the features and clinical significance of retinal macroaneurysm. Two groups can be defined: those with acute aneurysmal decompensation, Group I; and those with chronic aneurysmal decompensation, Group II. Haemorrhage is the main feature of the former group and exudates of the latter. Systemic and local associations are noted, and guidelines for treatment by phototherapy are discussed.


Glycerinated muscle fibers: relation between isometric tension and adenosine triphosphate hydrolysis.
The isometric tension of glycerinated muscle fibers and the adenosine triphosphatase activity of homogenates were determined as a function of the concentration of adenosine triphosphate without the addition of divalent cations. These two phenomena are not parallel; large tensions can be developed with negligible hydrolysis of adenosine triphosphate. It is concluded that the large negative free energy change of the hydrolysis is not required for shortening or development of tension.


Generation of ligand-based pharmacophore model and virtual screening for identification of novel tubulin inhibitors with potent anticancer activity.
A pharmacophore model, Hypo1, was built on the basis of 21 training-set indole compounds with varying levels of antiproliferative activity. Hypo1 possessed important chemical features required for the inhibitors and demonstrated good predictive ability for biological activity, with high correlation coefficients of 0.96 and 0.89 for the training-set and test-set compounds, respectively. Further utilization of the Hypo1 pharmacophore model to screen chemical database in silico led to the identification of four compounds with antiproliferative activity. Among these four compounds, 43 showed potent antiproliferative activity against various cancer cell lines with the strongest inhibition on the proliferation of KB cells (IC(50) = 187 nM). Further biological characterization revealed that 43 effectively inhibited tubulin polymerization and significantly induced cell cycle arrest in G(2)-M phase. In addition, 43 also showed the in vivo-like anticancer effects. To our knowledge, 43 is the most potent antiproliferative compound with antitubulin activity discovered by computer-aided drug design. The chemical novelty of 43 and its anticancer activities make this compound worthy of further lead optimization.


Principal angle spectroscopic ellipsometry utilizing a rotating analyzer.
The variations of the intensity of the reflected light near null as a function of the angle of incidence are compared for three ellipsometric techniques. For films of either SiO(2) or Si(3)N(4) on silicon, the highest accuracy of the film thickness measurement is always obtained when the angle of incidence is either equal or nearly equal to the principal angle for all thicknesses of the film layer. Based on these results, it is shown that a variable angle of incidence spectroscopic ellipsometer operated at the principal angle of incidence and using a rotating analyzer combines the advantage of versatility with near maximum accuracy and sensitivity.


Lack of interferon-gamma receptor does not influence the outcome of infection in murine schistosomiasis mansoni.
Studies of vaccine-induced immunity in experimental schistosomiasis in mice have suggested that interferon-gamma (IFN-gamma) is an important factor for the induction of protective immunity against schistosomiasis. The present study compares some parameters during primary schistosome infection in IFN-gamma receptor deficient mice and wild type mice. No significant difference in worm burden between the two groups was found. Almost the same number of eggs in the liver as well as typical granulomas with numerous macrophages and eosinophils were observed in both groups of mice. Furthermore, IFN-gamma receptor deficient mice infected with S. mansoni displayed a significant reduction in the number of IgG2a secreting cells in the spleen and a significant enhancement of IgA secreting cells in the spleen and in the lungs. These findings suggest that the lack of IFN-gamma activity may result in an enhanced dominance of Th2 cells which, however, does not influence the development of a primary schistosome infection.


Olfactory Loss and Regain: Lessons for Neuroplasticity.
For the visual and auditory senses, an array of studies has reported on neuronal reorganization processes after sensory loss. In contrast to this, neuroplasticity has been investigated only scarcely after loss of the olfactory sense. The present review focuses on the current extent of literature on structural and functional neuroplasticity effects after loss, with a focus on magnetic resonance imaging-based studies. We also include findings on the regain of the olfactory sense, for example after successful olfactory training. Existing studies indicate that widespread structural changes beyond the level of the olfactory bulb occur in the brain after loss of the olfactory sense. Moreover, on a functional level, loss of olfactory input not only entails changes in olfaction-related brain regions but also in the trigeminal system. Existing evidence should be strengthened by future longitudinal studies, a more thorough investigation of the neuronal consequences of congenital anosmia, and the application of state-of-the-art neuroimaging methods, such as connectivity analyses and joint analyses of brain structure and function.


Low dose high frequency ultrasound therapy for stellate ganglion blockade in complex regional pain syndrome type I: a randomised placebo controlled trial.
We aimed to determine the sympatholytic and clinical effects of low dose high frequency ultrasound (US) applied on stellate ganglion in Complex Regional Pain Syndrome (CRPS) type I patients. Fourty-five patients with CRPS type I were randomly allocated into three groups. Pharmacological treatment, transcutaneous electrical nerve stimulation (TENS), contrast bath and exercise were applied to all groups for 20 sessions. In addition to this treatment protocol, low dose high frequency US was applied on stellate ganglion as 0.5 watts/cm(2) in group I; 3 watts/cm(2) in group II and as placebo in group III. Forty age and sex matched healthy controls were served as controls. Sympathetic skin response (SSR) was used for determining the sympatholytic effects of US. Pain was assessed with visual analog scale (VAS), limitation of total finger flexion was assessed with finger pulp-distal crease distance, muscle strength was assessed with measuring the grip strength, upper extremity disability was assessed with Disability of the Arm, Shoulder and Hand (DASH) scale before and after the treatment. All groups evalueted in terms of VAS score, finger pulp-distal crease distance, grip strength and DASH score after the treatment. The improvements in those parameters were not statistically significant between the groups (P > 0.05). SSR latency was significantly shorter in CRPS patients than controls (P < 0.05). Pre- and post-treatment SSR amplitude and latency values were not different within patient groups (P > 0.05). The differences in pre- and post-treatment SSR amplitude and latency values were not statistically different between patient groups (P > 0.05). Low dose high frequency US applied on stellate ganglion did not make a sympathetic blockade and was not of further benefit for pain, range of motion, grip strength and upper extremity disability in CRPS type I patients.


Estradiol and testosterone secretion by human, simian, and canine testes, in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome.
The role of the human testis in the production of 17beta-estradiol (E(2)) was investigated by determining the concentration of E(2) and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E(2) was measured by radioimmunoassay utilizing sheep anti-E(2) serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1+/-0.74 (SEM) pg for deionized water and 13.1+/-0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17+/-0.71 pg/ml and 95+/-6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18+/-1.4 pg/ml. In the eight normal men, the mean peripheral vein E(2) concentration was 20+/-1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049+/-57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E(2) concentrations (160, 280, and 416 pg/ml). Lesser E(2) gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E(2) gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E(2) concentrations did not differ from control values. Spermatic vein E(2) concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E(2) and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E(2) and testosterone. These studies provide direct evidence that the human testic secretes estradiol.


The in vitro destruction of rumen fluid carotenoids by plant lipoxygenases.
An ability to destroy carotenoids in the rumen of cattle may be an effective method of limiting their absorption from the small intestine which, in turn, is likely to result in reduced adipose tissue colour. Plant lipoxygenases are well known for their ability to bleach beta-carotene. As lutein is the major carotenoid present in most forage grasses, we have investigated the bleaching of lutein as well as beta-carotene by lipoxygenase isolated from soybeans. In vitro studies, using micellar preparations of carotenoids, indicated that lutein was rapidly oxidised and that the progress of the reaction was similar to that observed for beta-carotene. The polyunsaturated fatty acid linoleate was essential. When bovine rumen fluid was used as a source of carotenoid for in vitro studies with preparations of lipoxygenase, a rapid decrease in carotenoid and chlorophyll concentrations was observed, again requiring the addition of linoleic acid. The direct addition of soya flour to bovine rumen fluid resulted in the effective bleaching of the pigments without the inclusion of linoleate. When compared with flours from a variety of other plant sources, soya flour was most effective. The inclusion of dietary sources of lipoxygenase may be an effective method for controlling carotenoid uptake in certain ruminant species.


Immunochemical detection of CoA-modified mitochondrial matrix proteins.
An in vitro assay mixture consisting of mitochondrial matrix proteins from rat liver and CoA resulted in the formation of CoA-modified proteins. CoA-modified proteins were demonstrated by detection of CoA. CoA was released from the proteins by dithioerythritol treatment under denaturing conditions and was identified by (a) its retention time on HPLC, (b) its absorption spectrum and (c) its activity in a CoA-specific assay. This CoA represents protein-bound CoA and, in addition, protein-bound palmitoyl-CoA when MgATP was also present in the in vitro assay. The detection of immunoreactive proteins using mono-specific anti-CoA antibodies exclusively identifies CoA-modified proteins. The specificity of these antibodies can be used to identify both endogenously occurring CoA-modified proteins and proteins that have been modified in the in vitro assay. An intact thiol group of CoA is an essential precondition for the modification to occur.


Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial.
We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003). Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.


Is there a role for macrolides in severe asthma?
Severe asthma is a heterogeneous syndrome, encompassing several distinct clinical phenotypes. Different molecular and cellular pathways or endotypes determine the type of underlying airway inflammation in patients with severe asthma, which can be categorized as eosinophilic asthma (allergic and nonallergic) or noneosinophilic asthma (neutrophilic and paucigranulocytic). In this review, we discuss the potential role of macrolides in the treatment of severe asthma in adults. Maintenance treatment with low-dose macrolides such as erythromycin and azithromycin provides clinical benefit in several chronic neutrophilic airway diseases, including cystic fibrosis (CF), non-CF bronchiectasis and exacerbation-prone chronic obstructive pulmonary disease. Although several short-term studies of macrolides in mild-to-moderate asthma have failed to improve lung function, the AzIthromycin in Severe Asthma trial has demonstrated a significant reduction in the rate of exacerbations in patients with exacerbation-prone noneosinophilic severe asthma. As chronic macrolide use is associated with the risks of population antimicrobial resistance, this add-on treatment should be restricted to severe asthma patients at greatest unmet need despite optimal asthma management. Further clinical, translational and basic research is needed to better phenotype patients with severe asthma, to determine the risk-benefit ratio of macrolide maintenance treatment in neutrophilic severe asthma and to elucidate the principal mechanisms of action of macrolides.


GhFB15 is an F-box protein that modulates the response to salinity by regulating flavonoid biosynthesis.
An exposure to extremely saline conditions can lead to significant oxidative damage in plants. Flavonoids, which are potent antioxidants, are critical for the scavenging of reactive oxygen species caused by abiotic stress. In the present study, the cotton F-box gene GhFB15 was isolated and characterized. The expression of GhFB15 was rapidly induced by salt as well as by exogenous hormones (ETH, MeJA, ABA, and GA). An analysis of subcellular localization revealed GhFB15 is mainly distributed in nuclei. Overexpression of GhFB15 adversely affected the salt tolerance of transgenic Arabidopsis plants as evidenced by decreased seed germination and seedling growth, whereas the silencing of GhFB15 improved the salt tolerance of cotton plants. Furthermore, we analyzed the gene expression profiles of VIGS-GhFB15 and TRV:00 plants. Many of the differentially expressed genes were associated with the flavonoid biosynthesis pathway. Moreover, lower flavonoid contents and higher levels of H2O2 and O2- were observed in the transgenic Arabidopsis plants. Conversely, the VIGS-GhFB15 cotton plants had relatively higher flavonoid contents, but lower H2O2 and O2- levels. These results suggest that GhFB15 negatively regulates salt tolerance, and silencing GhFB15 results in increased flavonoid accumulation and improved ROS scavenging.


O-antigen structural variation: mechanisms and possible roles in animal/plant-microbe interactions.
Current data from bacterial pathogens of animals and from bacterial symbionts of plants support some of the more general proposed functions for lipopolysaccharides (LPS) and underline the importance of LPS structural versatility and adaptability. Most of the structural heterogeneity of LPS molecules is found in the O-antigen polysaccharide. In this review, the role and mechanisms of this striking flexibility in molecular structure of the O-antigen in bacterial pathogens and symbionts are illustrated by some recent findings. The variation in O-antigen that gives rise to an enormous structural diversity of O-antigens lies in the sugar composition and the linkages between monosaccharides. The chemical composition and structure of the O-antigen is strain-specific (interstrain LPS heterogeneity) but can also vary within one bacterial strain (intrastrain LPS heterogeneity). Both LPS heterogeneities can be achieved through variations at different levels. First of all, O-polysaccharides can be modified non-stoichiometrically with sugar moieties, such as glucosyl and fucosyl residues. The addition of non-carbohydrate substituents, i.e. acetyl or methyl groups, to the O-antigen can also occur with regularity, but in most cases these modifications are again non-stoichiometric. Understanding LPS structural variation in bacterial pathogens is important because several studies have indicated that the composition or size of the O-antigen might be a reliable indicator of virulence potential and that these important features often differ within the same bacterial strain. In general, O-antigen modifications seem to play an important role at several (at least two) stages of the infection process, including the colonization (adherence) step and the ability to bypass or overcome host defense mechanisms. There are many reports of modifications of O-antigen in bacterial pathogens, resulting either from altered gene expression, from lysogenic conversion or from lateral gene transfer followed by recombination. In most cases, the mechanisms underlying these changes have not been resolved. However, in recent studies some progress in understanding has been made. Changes in O-antigen structure mediated by lateral gene transfer, O-antigen conversion and phase variation, including fucosylation, glucosylation, acetylation and changes in O-antigen size, will be discussed. In addition to the observed LPS heterogeneity in bacterial pathogens, the structure of LPS is also altered in bacterial symbionts in response to signals from the plant during symbiosis. It appears to be part of a molecular communication between bacterium and host plant. Experiments ex planta suggest that the bacterium in the rhizosphere prepares its LPS for its roles in symbiosis by refining the LPS structure in response to seed and root compounds and the lower pH at the root surface. Moreover, modifications in LPS induced by conditions associated with infection are another indication that specific structures are important. Also during the differentiation from bacterium to bacteroid, the LPS of Rhizobium undergoes changes in the composition of the O-antigen, presumably in response to the change of environment. Recent findings suggest that, during symbiotic bacteroid development, reduced oxygen tension induces structural modifications in LPS that cause a switch from predominantly hydrophilic to predominantly hydrophobic molecular forms. However, the genetic mechanisms by which the LPS epitope changes are regulated remain unclear. Finally, the possible roles of O-antigen variations in symbiosis will be discussed.


An alternative sigma factor governs the principal sigma factor in Streptomyces griseus.
In bacteria, the RNA polymerase holoenzyme comprises a five-subunit core enzyme and a dissociable subunit, sigma factor, which is responsible for transcriptional initiation. The filamentous bacterium Streptomyces griseus has 52 sigma factors, including one essential 'principal' sigma factor (σ(HrdB) ) that is responsible for the transcription of housekeeping genes. Here we characterized an alternative sigma factor (σ(ShbA) ), which is highly conserved within the genus Streptomyces. A σ(ShbA) -deficient mutant showed a severe growth defect and transcriptome analysis indicated that many housekeeping genes were downregulated in response to insufficient σ(ShbA) production. Biochemical and genetic analyses proved that σ(ShbA) is a major determinant of transcription of the σ(HrdB) gene. This observation of a principal sigma factor being governed by another sigma factor throughout growth is unprecedented. We found that increasing σ(ShbA) production with mycelial growth maintained a high σ(HrdB) level late in growth. Furthermore, a hrdB-autoregulatable σ(ShbA) -deficient mutant, in which the principal sigma factor gene can be transcribed by RNA polymerase containing σ(HrdB) itself, showed several defects: rapid mycelial lysis in stationary phase in liquid culture and delayed morphological development and impaired streptomycin production in solid culture. From these observations, we discuss the biological significance of control of σ(HrdB) by σ(ShbA) in S. griseus.


[Saint Anthony's Fire or gangrenous ergotism and its medieval iconography].
The frequent epidemics of ergotism were called Holy Fire or st-Antony's Fire in the Middle Ages, because of the burning sensations resulting in gangrene of limbs. It was caused by eating rye bread contaminated with the fungus Claviceps purpurea. The hospitable Order of st-Antony was founded near Vienne in France with 300 establishements in Europe until 1777. In coptic and byzantine art st-Antony is the father of the monks, whereas in Occident he is the the master of fire, thaumaturgic, resulting a very important iconography in statuary and painworks in all regions, especially in Lorraine, the catholic and tridentin Lotharingia and in Corsica thanks to the franciscan pastoral. Woodcuts show not only the temptations of st-Antony, with strange and diabolic scenes, patients with gangrenous limbs. Germanic woodcuts of the 15th century show patients with different stages of ergotism and hands and feet like ex-voto. Triptycs of H. Bosch and M. Gunewald are witnesses of the frequency and seriousness of this disease still at the beginning of the 16th century.


Chemotaxonomic Classification Applied to the Identification of Two Closely-Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics.
This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages. Metabolomics can capture a comprehensive analysis of small molecule metabolites and can provide a powerful approach to establish metabolic profiling, creating a bridge between genotype and phenotype. To further investigate the different metabolites in four closely-related Citrus TCMs, non-targeted metabolite profiling analysis was employed as an efficient technique to profile the primary and secondary metabolites. The results presented in this manuscript indicate that primary metabolites enable the discrimination of species, whereas secondary metabolites are associated with species and the ripening process. In addition, analysis of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages. Ultimately, this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses.


Selective attention and recognition: effects of congruency on episodic learning.
Recent research on cognitive control has focused on the learning consequences of high selective attention demands in selective attention tasks (e.g., Botvinick, Cognit Affect Behav Neurosci 7(4):356-366, 2007; Verguts and Notebaert, Psychol Rev 115(2):518-525, 2008). The current study extends these ideas by examining the influence of selective attention demands on remembering. In Experiment 1, participants read aloud the red word in a pair of red and green spatially interleaved words. Half of the items were congruent (the interleaved words had the same identity), and the other half were incongruent (the interleaved words had different identities). Following the naming phase, participants completed a surprise recognition memory test. In this test phase, recognition memory was better for incongruent than for congruent items. In Experiment 2, context was only partially reinstated at test, and again recognition memory was better for incongruent than for congruent items. In Experiment 3, all of the items contained two different words, but in one condition the words were presented close together and interleaved, while in the other condition the two words were spatially separated. Recognition memory was better for the interleaved than for the separated items. This result rules out an interpretation of the congruency effects on recognition in Experiments 1 and 2 that hinges on stronger relational encoding for items that have two different words. Together, the results support the view that selective attention demands for incongruent items lead to encoding that improves recognition.


Tissue changes of extraction sockets in humans: a comparison of spontaneous healing vs. ridge preservation with secondary soft tissue healing.
As a consequence of extraction, the height of the buccal wall tends to decrease and results in the disappearance of bundle bone. To modify bone remodelling after extraction, various ridge preservation techniques have been proposed. The present research was drawn up with the following considerations in mind: to evaluate and to compare changes of hard and soft tissues in post-extraction sockets which received a ridge preservation procedure, with post-extraction sockets which had healed naturally. Each patient was randomly allocated to a test or control group using a specific software package. After extraction, the sockets were carefully inspected and any granulation tissue was removed. The control sites received silk sutures to stabilize the clot without any grafting material. The test sites were grafted with corticocancellous porcine bone and a collagen membrane. All experimental sites had the membranes left exposed to the oral cavity with a secondary wound healing. The thickness of the buccal alveolar bone, if present, was carefully measured at the time of tooth extraction using a calliper at 1 mm from the edge of the wall. The following clinical parameters were evaluated at baseline and after 4 months at implant placement: vertical bone changes, horizontal bone changes and width of keratinized gingiva. The length, diameter and need for additional bone augmentation were assessed for both groups at the time of implant insertion. The control group showed vertical bone resorption of 1 ± 0.7 mm, 2.1 ± 0.6 mm, 1 ± 0.8 mm and 2 ± 0.73 mm at the mesial, vestibular, distal and lingual sites respectively. Moreover, changes in horizontal dimension showed an average resorption of 3.6 ± 0.72 mm. The test sites showed a horizontal bone remodelling of 0.3 ± 0.76 mm, 1.1 ± 0.96 mm, 0.3 ± 0.85 mm, 0.9 ± 0.98 mm at the mesial, vestibular, distal and lingual sites respectively. The horizontal bone resorption at the test sites was 1.6 ± 0.55 mm. The keratinized gingiva showed a coronal shift of 0.7 mm in the control group when compared to 1.1 mm in the test group. In addition, 42% of sites in the control group required an additional bone augmentation at implant placement, when compared to 7% in the test sites. This study clearly points out that an alveolar ridge preservation technique performed with collagenated porcine bone and a resorbable membrane--according to the procedure reported in this study--was able to limit the contour changes after tooth extraction. Finally, the test sites showed a better preservation of facial keratinized tissue when compared to control sites; grafted sites allowed the placement of longer and wider implants when compared to implants inserted in non-grafted sites.


Variability in the ocular phenotype in mucopolysaccharidosis.
Mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. Ocular complications (such as corneal clouding, retinopathy and optic neuropathy) are common. Notably, there is a paucity of data on the effect of genotype and systemic treatments (enzyme replacement therapy or haematopoietic stem cell transplantation) on the ocular phenotype in MPS. We prospectively studied the ocular features of patients with MPSI (Hurler/Hurler-Scheie/Scheie), MPSIV (Morquio) and MPSVI (Maroteaux-Lamy), to evaluate the effect of different therapeutic interventions and to correlate the findings with genetic and biomarker data. Prospective observational cohort study. Study participants underwent detailed ocular examination including visual acuity; assessment of corneal clouding (Iris camera Corneal Opacification Measure score and Pentacam densitometry) and retinal and optic nerve imaging (optical coherence tomography and wide-field fundus imaging). Data on genotype, biomarkers and delivered therapies (type and length of treatment) were also collected for each patient where available. Overall, 21 patients with MPSI, 4 patients with MPSIV and 3 patients with MPSVI were recruited. Corneal clouding scores were higher in MPSI compared with MPSIV and MPSVI. Retinopathy was evident in patients with MPSI only. Association was observed between corneal clouding and biomarkers in MPSI, MPSIV and MPSVI. However, no clear association was seen between genotype or treatment type and ocular phenotype. The ocular phenotype in MPS is variable, with corneal clouding occurring in MPSI, MPSIV and MPSVI, and retinopathy in MPSI only. There was an association between corneal clouding and efficacy of systemic treatment as measured by biomarkers.


[Use of Clinical Practice Guidelines in Daily Practice].
Clinical practice guidelines aim to improve patients' outcomes by providing recommendations for key clinical issues with alternative care options. Improvement in healthcare quality can be expected by applying clinical practice guidelines to daily practice for appropriate decision-making by patients and practitioners. Integration of clinical practice guidelines with the original articles, textbooks, and experiences, together with the patient's personal situation, is essential for the appropriate use of clinical practice guidelines.


Direct Fabrication of PET-Based Thermotolerant Separators for Lithium-Ion Batteries with Ion Irradiation Technology.
Lithium-ion batteries (LIBs) play a pivotal role as essential components in various applications, including mobile devices, energy storage power supplies, and electric vehicles. The widespread utilization of LIBs underscores their significance in the field of energy storage. High-performance LIBs should exhibit two key characteristics that have been persistently sought: high energy density and safety. The separator, a critical part of LIBs, is of paramount importance in ensuring battery safety, thus requiring its high thermal stability and uniform nanochannels. Here, the novel ion-track etched polyethylene terephthalate (ITE PET) separator is controllably fabricated with ion irradiation technology. Unlike conventional polypropylene (PP) separators, the ITE PET separator demonstrated vertically aligned nanochannels with uniform channel size and distribution. The remarkable characteristics of the ITE PET separator include not only high electrolyte wettability but also exceptional thermal stability, capable of withstanding temperatures as high as 180 °C. Furthermore, the ITE PET separator exhibits a higher lithium-ion transfer number (0.59), which is advantageous in enhancing battery performance. The structural and inherent advantages of ITE PET separators contribute to enhance the C-rate capacity, electrochemical, and long-term cycling (300 cycles) stability observed in the corresponding batteries. The newly developed method for fabricating ITE PET separators, which possess high thermal stability and a uniform channel structure, fulfills the demand for high-temperature-resistant separators without requiring any modification procedures. Moreover, this method can be easily scaled up using simple processes, making it a competitive strategy for producing thermotolerant separators.


A new antireflux procedure at the esophagogastric junction: experimental and clinical evaluation.
In posterior fundoplasty, a derivative of Nissen fundoplication, the fundus is passed behind the abdominal esophagus and fixed to the anterior aspect of the stomach, thus modifying the angle of entrance of the esophagus, creating a posterior gastric reservoir relatively inaccessible to the cardia. In dogs, it was a successful as a Nissen fundoplication in reversing esophagitis caused by reflux and daily administration of histamine. In another group of dogs, a cylindrical resection of the last 4 or 6 cm of the esophagus and a posterior fundoplasty were performed simultaneously. In spite of the daily administration of 30 mg of histamine, none of the dogs developed esophagitis. Posterior fundoplasty has proved effective in 14 patients with hiatal hernia observed for three years. In five patients undergoing a Heller myotomy for achalasia, it was used successfully to prevent postoperative regurgitation.


[Bilateral spontaneous renal pelvis rupture during a computed tomography: Report of one case].
Spontaneous rupture of the urinary excretory system is a rare condition. It is mainly associated with obstruction of the excretory system and is usually unilateral. We report a 58 years old male who, during the performance of a computed tomography of the urinary system, felt an intense lumbar pain. A bilateral rupture at the level of the fornix was found. The patient had an uneventful evolution thereafter. Fifteen days later a new computed tomography showed indemnity of the urinary excretory system.


In vivo and in vitro recombination of lambda DNA in CaC12 transfection.
Using CaCl2 mediated transfection with Lambda DNA fragments, in vitro joining by ligase and in vivo recombination with helper phage DNA are effective systems for generating artificial recombinants. Recombination efficiencies are 20--30% in the in vitro and in vivo recombination systems. At 30 to 37 degree C T4 ligase mainly joins natural cohesive alpha ends, while at 12 degrees C the EcoRI-generated termini are preferentially ligated to form biologically active molecules, if the cloning vector alpha 401 is used, which has only one EcoRI target. The ligation products were characterized by gel electrophoresis and CaCl2 transfection. For in vivo recombination a new CaCl2 transfection system was developed, termed postinfection-dependent CaCl2 transfection system, which is based on the infection of recipient cells with helper phages after transfection. In marker rescue experiments using this method not only single but also double recombination occurred between two independent alpha DNA fragments and the helper phage DNA.


Reversal of human cytomegalovirus major immediate-early enhancer/promoter silencing in quiescently infected cells via the cyclic AMP signaling pathway.
The human cytomegalovirus (HCMV) major immediate-early (MIE) enhancer contains five functional cyclic AMP (cAMP) response elements (CRE). Because the CRE in their native context do not contribute appreciably to MIE enhancer/promoter activity in lytically infected human fibroblasts and NTera2 (NT2)-derived neurons, we postulated that they might have a role in MIE enhancer/promoter reactivation in quiescently infected cells. Here, we show that stimulation of the cAMP signaling pathway by treatment with forskolin (FSK), an adenylyl cyclase activator, greatly alleviates MIE enhancer/promoter silencing in quiescently infected NT2 neuronal precursors. The effect is immediate, independent of de novo protein synthesis, associated with the phosphorylation of ATF-1 serine 63 and CREB serine 133, dependent on protein kinase A (PKA) and the enhancer's CRE, and linked to viral-lytic-cycle advancement. Coupling of FSK treatment with the inhibition of either histone deacetylases or protein synthesis synergistically activates MIE gene expression in a manner suggesting that MIE enhancer/promoter silencing is optimally relieved by an interplay of multiple regulatory mechanisms. In contrast, MIE enhancer/promoter silence is not overcome by stimulation of the gamma interferon (IFN-gamma) signaling pathway, despite the enhancer having two IFN-gamma-activated-site-like elements. We conclude that stimulation of the cAMP/PKA signaling pathway drives CRE-dependent MIE enhancer/promoter activation in quiescently infected cells, thus exposing a potential mode of regulation in HCMV reactivation.


An empirical assessment of the factors influencing acceptance of COVID-19 vaccine uptake between Kenyan and Hungarian residing populations: A cross-sectional study.
The development of effective, safe, and acceptable vaccines is a long process. COVID-19 vaccine hesitancy continues to elicit mixed reactions among different quarters despite numerous evidence of their effectiveness. This study aimed to determine the availability and acceptance rates of SARS-CoV-2 vaccines, among Kenyan and Hungarian residing populations and the underlying reasons contributing to the hesitancy of uptake. A non-probability, snowball sampling design was employed, and a survey questionnaire tool link was expeditiously disseminated. Data were carefully analyzed descriptively. Demographic variables, COVID-19 awareness, possible exposure, reasons associated with hesitancy in taking up a vaccine, choice of a vaccine, and availability of vaccines among other important variables were tested to explore their associations with vaccine acceptance rates between the two distinct countries. A total of 1960 participants were successfully enrolled in the research study, while 67 participants were excluded based on the inclusion criterion set. There was, however, no significant difference in COVID-19 public awareness between the Kenyan and Hungarian-residing participants, p = 0.300. Of the respondents, 62.4% were willing and ready to receive vaccines against COVID-19 disease. There was a significant difference (p = 0.014) between the Kenyan and Hungarian-residing respondents concerning vaccine uptake and acceptance rates. The vaccine acceptance rates in Hungary were higher than in Kenya, with mean = 0.27, SD = 0.446, S. E = 0.045 for the Hungarian population sample and mean = 0.40, SD = 0.492, S. E = 0.026, for the Kenyan sample respectively. Concerning gender and vaccine acceptance, there was a notable significant difference between males and females, p = 0.001, where the mean for males and females were 0.29 and 0.46 respectively. Acceptance rates among males were higher than among females. The functions of One-Way ANOVA and Chi-square were used to establish any significant differences and associations between means and variables respectively. Concerns regarding the safety, efficacy, and accuracy of information about the developed vaccines are significant factors that must be promptly addressed, to arrest crises revolving around COVID-19 vaccine hesitancy, especially in Kenya and among females in both populations, where acceptance rates were lower. Expansion of the screening program to incorporate antibody (serology) tests, is also highly recommended in the present circumstance. Equitable distribution of vaccines globally should be encouraged and promoted to adequately cover low- and middle-income countries. To enhance effective combat on vaccination hesitancy and apprehension in different countries, mitigation techniques unique to those countries must be adopted.


Predicting Drug-Induced Liver Injury with Bayesian Machine Learning.
Drug induced liver injury (DILI) can require significant risk management in drug development and on occasion can cause morbidity or mortality, leading to drug attrition. Optimizing candidates preclinically can minimize hepatotoxicity risk, but it is difficult to predict due to multiple etiologies encompassing DILI, often with multifactorial and overlapping mechanisms. In addition to epidemiological risk factors, physicochemical properties, dose, disposition, lipophilicity, and hepatic metabolic function are also relevant for DILI risk. Better human-relevant, predictive models are required to improve hepatotoxicity risk assessment in drug discovery. Our hypothesis is that integrating mechanistically relevant hepatic safety assays with Bayesian machine learning will improve hepatic safety risk prediction. We present a quantitative and mechanistic risk assessment for candidate nomination using data from in vitro assays (hepatic spheroids, BSEP, mitochondrial toxicity, and bioactivation), together with physicochemical (cLogP) and exposure (Cmaxtotal) variables from a chemically diverse compound set (33 no/low-, 40 medium-, and 23 high-severity DILI compounds). The Bayesian model predicts the continuous underlying DILI severity and uses a data-driven prior distribution over the parameters to prevent overfitting. The model quantifies the probability that a compound falls into either no/low-, medium-, or high-severity categories, with a balanced accuracy of 63% on held-out samples, and a continuous prediction of DILI severity along with uncertainty in the prediction. For a binary yes/no DILI prediction, the model has a balanced accuracy of 86%, a sensitivity of 87%, a specificity of 85%, a positive predictive value of 92%, and a negative predictive value of 78%. Combining physiologically relevant assays, improved alignment with FDA recommendations, and optimal statistical integration of assay data leads to improved DILI risk prediction.


Climate of origin affects tick (Ixodes ricinus) host-seeking behavior in response to temperature: implications for resilience to climate change?
Climate warming is changing distributions and phenologies of many organisms and may also impact on vectors of disease-causing pathogens. In Europe, the tick Ixodes ricinus is the primary vector of medically important pathogens (e.g., Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis). How might climate change affect I. ricinus host-seeking behavior (questing)? We hypothesize that, in order to maximize survival, I. ricinus have adapted their questing in response to temperature in accordance with local climates. We predicted that ticks from cooler climates quest at cooler temperatures than those from warmer climates. This would suggest that I. ricinus can adapt and therefore have the potential to be resilient to climate change. I. ricinus were collected from a cline of climates using a latitudinal gradient (northeast Scotland, North Wales, South England, and central France). Under laboratory conditions, ticks were subjected to temperature increases of 1°C per day, from 6 to 15°C. The proportion of ticks questing was recorded five times per temperature (i.e., per day). The theoretical potential to quest was then estimated for each population over the year for future climate change projections. As predicted, more ticks from cooler climates quested at lower temperatures than did ticks from warmer climates. The proportion of ticks questing was strongly associated with key climate parameters from each location. Our projections, based on temperature alone, suggested that populations could advance their activity season by a month under climate change, which has implications for exposure periods of hosts to tick-borne pathogens. Our findings suggest that I. ricinus have adapted their behavior in response to climate, implying some potential to adapt to climate change. Predictive models of I. ricinus dynamics and disease risk over continental scales would benefit from knowledge of these differences between populations.


Integrated microRNA and mRNA responses to acute human left ventricular ischemia.
MicroRNAs (miRNAs) play a significant role in ischemic heart disease. Animal models of left ventricular (LV) ischemia demonstrate a unique miRNA profile; however, these models have limitations in describing human disease. In this study, we performed next-generation miRNA and mRNA sequencing on LV tissue from nine patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. Samples were obtained immediately after aortic cross clamping (baseline) and before aortic cross clamp removal (postischemic). Of 1,237 identified miRNAs, 21 were differentially expressed between baseline and postischemic LV samples including the upregulated miRNAs miR-339-5p and miR-483-3p and the downregulated miRNA miR-139-5p. Target prediction analysis of these miRNAs was integrated with mRNA expression from the same LV samples to identify anticorrelated miRNA-mRNA pairs. Gene enrichment studies of candidate mRNA targets demonstrated an association with cardiovascular disease, cell death, and metabolism. Therapeutics that intervene on these miRNAs and their downstream targets may lead to novel mechanisms of mitigating the damage caused by ischemic insults on the human heart.


Sentiment correlation in financial news networks and associated market movements.
In an increasingly connected global market, news sentiment towards one company may not only indicate its own market performance, but can also be associated with a broader movement on the sentiment and performance of other companies from the same or even different sectors. In this paper, we apply NLP techniques to understand news sentiment of 87 companies among the most reported on Reuters for a period of 7 years. We investigate the propagation of such sentiment in company networks and evaluate the associated market movements in terms of stock price and volatility. Our results suggest that, in certain sectors, strong media sentiment towards one company may indicate a significant change in media sentiment towards related companies measured as neighbours in a financial network constructed from news co-occurrence. Furthermore, there exists a weak but statistically significant association between strong media sentiment and abnormal market return as well as volatility. Such an association is more significant at the level of individual companies, but nevertheless remains visible at the level of sectors or groups of companies.


Spinal cord regeneration: a phenomenon unique to urodeles?
Studies of neuronal survival and axonal regeneration in birds and mammals have made it clear that the microenvironment of the CNS is critical to the failure of CNS regeneration in these animals. This environment includes growth and trophic factors, ECM components and matrix turnover enzymes, cytokines and other immune system contributions. Urodele amphibians (salamanders and newts) can regenerate spinal cord even as adults, and environmental contributions of glial populations are a major part of the difference between urodele and higher vertebrate spinal cord regeneration. In particular, the behavior of injury-reactive ependymal cells (radial glia) is critical to the regenerative capacity of urodele spinal cord. In this review we examine what is known about cell-cell interactions between ependymal cells and neurons and between ependymal cells and other glial populations. The known contributions of ependymal cell products such as matrix metalloproteinases and trophic factors are discussed. There is evidence in the literature that an ependymal response occurs during embryonic or fetal development in birds and mammals following spinal cord transection, and this review discusses the implications of such a process for future studies of spinal cord injury.


Effects of abattoir and slaughter handling systems on stress indicators in pig blood.
Pigs from four farms were slaughtered at two abattoirs, each with two slaughter handling systems. Pigs at abattoir X were electrically stunned, either in a floor pen holding five pigs or in a race-restrainer. At abattoir Y pigs were stunned either in a floor pen holding five pigs or in a dip-lift carbon dioxide stunner. At exsanguination, 96 blood samples (24/farm) were collected from pigs slaughtered through each slaughter handling system (384 samples in total). Serum samples were analysed for cortisol, creatine phosphokinase (CPK) lactate dehydrogenase (LDH) and LDH-isoenzymes. There were no significant differences between the systems at abattoir X. At abattoir Y, pigs slaughtered through the floor pen system had higher levels of LDH-5 (39.84 +/- 1.39 per cent of total LDH vs 34.76 +/- 1.21 per cent, P < 0.05) indicating greater skeletal muscle damage in the floor pen. Pigs at abattoir Y had higher mean serum levels of CPK than pigs at abattoir X (3.63 log10 U/litre vs 3.41 log10 U/litre, 0.03 sed, P < 0.001), higher total LDH activities (1269.5 U/litre vs 922.8 U/litre, P < 0.001) and higher cortisol concentrations (1.70 log10 ng/ml vs 1.51 log10 ng/ml, P < 0.001). These differences suggested that the levels of physical and psychological stress were higher at abattoir Y.


Functional specificity of Sgk1 and Akt1 on ENaC activity.
Reabsorption of sodium by the epithelial sodium channel (ENaC) is essential for maintaining the volume of the extracellular compartment and blood pressure. The function of ENaC is regulated primarily by aldosterone, antidiuretic hormone [arginine vasopressin (AVP)], and insulin, but the molecular mechanisms that increase channel activity are still poorly understood. It has been proposed that the related serine/threonine kinases serum- and glucocorticoid-induced kinase (Sgk1) and protein kinase B (Akt) mediate activation of ENaC. Here, we addressed the question of whether there is functional specificity of these kinases for the activation of ENaC in epithelial cells of the distal renal tubule. We demonstrate that Akt does not increase ENaC function under basal conditions or after stimulation with aldosterone, insulin, or AVP. In contrast, under the same experimental conditions, Sgk1 increases ENaC activity by 10-fold. The effect of Sgk1 is additive to that of aldosterone, whereas, in the presence of active Sgk1, cells do not further respond to insulin or AVP. We conclude that, in cells expressing both kinases, modulation of ENaC activity is mediated by Sgk1 but not by Akt1.


Staphylococcal alpha-phenol soluble modulins contribute to neutrophil lysis after phagocytosis.
Staphylococcus aureus community-acquired (CA) MRSA strains are highly virulent and can cause infections in otherwise healthy individuals. The most important mechanism of the host for clearing S. aureus is phagocytosis by neutrophils and subsequent killing of the pathogen. Especially CA-MRSA strains are very efficient in circumventing this neutrophil killing. Interestingly, only a relative small number of virulence factors have been associated with CA-MRSA, one of which are the phenol soluble modulins (PSMs). We have recently shown that the PSMs are functionally inhibited by serum lipoproteins, indicating that PSMs may exert their cytolytic function primarily in the intracellular environment. To further investigate the intracellular role of the PSMs we measured the effect of the α-type and β-type PSMs on neutrophil killing after phagocytosis. Using fluorescently labelled S. aureus, we measured bacterial survival after phagocytosis in a plate reader, which was employed next to flow cytometry and time-lapse microscopy. Phagocytosis of the CA-MRSA strain MW2 by human neutrophils resulted in rapid host cell death. Using mutant strains of MW2, we demonstrated that in the presence of serum, the intracellular expression of only the psmα operon is both necessary and sufficient for both increased neutrophil cell death and increased survival of S. aureus. Our results identify PSMα peptides as prominent contributors to killing of neutrophils after phagocytosis, a finding with major implications for our understanding of S. aureus pathogenesis and strategies for S. aureus vaccine development.


MiRNAs Targeting Double Strand DNA Repair Pathways Lurk in Genomically Unstable Rare Fragile Sites and Determine Cancer Outcomes.
Double strand break (DSB) repair mechanisms guard genome integrity and their deterioration causes genomic instability. Common and rare fragile sites (CFS and RFS, respectively) are particularly vulnerable to instability, and there is an inverse correlation between fragile site (FS) expression and DSB repair protein levels. Upon DSB repair dysfunction, genes residing at these sites are at greater risk of deregulation compared to genes located at non-FS. In this regard, it remains enigmatic why the incidence of miRNA genes at FS is higher compared to non-FS. Herein, using bioinformatics, we examined whether miRNA genes localized at FS inhibit components of DSB repair pathways and assessed their effects on cancer. We show that such miRNAs over-accumulate in RFS, and that FRAXA, which is expressed in Fragile X syndrome, is a conserved hotspot for miRNAs inhibiting DSB repair. Axes of FRAXA-residing miRNAs/DSB repair targets affect survival in a cancer type-specific manner. Moreover, copy number variations in the region encompassing these miRNA genes discriminate survival between male and female patients. Given that, thus far, only CFS have been considered relevant for carcinogenesis, our data are the first to associate RFS with cancer, through the impairment of DSB repair by the FRAXA-residing miRNAs.


Association between serum uric acid and renal outcome in patients with biopsy-confirmed diabetic nephropathy.
To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L (n = 98); Q2 group: 358.23 ± 14.03 μmol/L (n = 99); Q3 group: 405.50 ± 14.59 μmol/L (n = 98) and Q4 group: 499.14 ± 56.97μmol/L (n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P = 0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621-2.992; P = 0.439), 1.518 (0.768-3.002; P = 0.230) and 1.411 (0.706-2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P = 0.652). No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.


[Sexual Behavior and Self-Efficacy for the Negotiation of Safer Sex in Heterosexual Persons.]
Self-efficacy has been defined as one of the factors that may facilitate or impede safer sex. Studies reveal that peoples in steady relationships practice safer sex less often that those in casual relationships. We conducted a study with 447 sexually active heterosexual adults. A self-administered questionnaire was designed to study the sexual behavior, the male condom use and the practice of mutual masturbation, and the self-efficacy toward these practices. Results show that most men are sexually active and that there is a low frequency of male condom use and the practice of mutual masturbation as safer sex. The majority of those who use the male condom are engage in casual relationships. However, participants have high levels of self-efficacy toward these practices. Although self-efficacy is one of the factors that influence in deciding to practice safer sex, it is not sufficient to reach this goal.


[Approach to venous diseases in the elderly].
Incidence and severity of both deep vein thrombosis and chronic venous insufficiency are increased with age. Today, however, the significance of these diseases in the elderly patient population are still poorly comprehended. Although most patients have a history of previous treatment, chronic venous insufficiency is usually encountered in the advanced clinical stage. As a result, there is an increase in mobility restrictions, the need for assistance in daily activities and the risk of falls in elderly patients. The quality of life is negatively affected in patients. Age, immobilization and obesity are the main risk factors for the development of chronic venous insufficiency in the elderly. Patients present with complaints such as pain, edema, burning, bloating, weight sensation, restless leg syndrome, night cramps, varicosities, color change and open wound in the legs. In diagnostic procedures, color Doppler ultrasonography examination is used together with patient's staging as well as history and physical examination. Classification of "Clinical-Etiology- Anatomy-Pathology (CEAP)" is used in defining venous insufficiency patients. Among the leading differential diagnoses are congestive heart failure, renal failure, liver dysfunction, antihypertensive, non-steroidal anti-inflammatory and some antidiabetic medications and lymphedema and deep vein thrombosis. Patients underwent early diagnosis and long-term regular follow-up after appropriate therapeutic interventions reduce the risk of developing advanced complicated clinical conditions. The main components of treatment include patient education, mobilization, leg elevation, prevention of obesity, use of venous compression stockings, use of venoactive agents, and catheterbased/ surgical interventions. Endovenous radiofrequency or laser ablation techniques and endovenous chemical ablation techniques in superficial venous insufficiency are preferential interventional modalities due to low morbidity risks in older age group of chronic superficial venous insufficiency patients. Foam sclerotherapy for superficial truncal varicosities can also be considered as an alternative for older age groups. In any treatment decision to be taken, the risk-benefit ratio, the patient's clinical status, the available treatment options as well as the patientspecific risks and the patient's expectation and decision should be the main determinant. It is important to remember that what is more important than the age of the patient is the patient's own physical condition and that the quality of life is improved.


Language preferences among callers to a regional Poison Center.
Providing service to non-English speaking populations is a common challenge facing Poison Centers (PC). Previous studies have identified that people who do not speak functional English are unlikely to call a PC. We developed a survey to determine the language preferences of poison center callers and to identify if we were failing to offer services in languages other than English to callers who felt they needed them. We surveyed 322 parents during routine callbacks about language spoken at home, first and second languages, country of birth, and satisfaction with language used by the PC. We found that 93% primarily spoke English, 5% spoke English and Spanish, and 5% spoke other languages at home in a region where approximately 10% of the population speak English poorly. The majority of respondents were born in the US and were comfortable using English when using the PC. There were 6 cases where callers would have preferred using a different language. Our study supports data suggesting that poison centers are underutilized by people that are recent immigrants and speak English poorly. Awareness programs and educational efforts should be directed toward this sub-population.


Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial.
Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/- octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. NCT00002864, http://clinicaltrials.gov/show/NCT00002864.


Tissue factor gene localized to human chromosome 1 (1pter----1p21).
Tissue factor (tissue thromboplastin, coagulation factor III), a protein component of cell membranes, is an essential cofactor for factor VII-dependent initiation of blood coagulation. Since no tissue factor-deficient condition has been described, it is one of only a few proteins of the coagulation system for which the pattern of inheritance has not been ascertained. Because of the species-specificity of tissue factor activity and the availability of a very sensitive chromogenic assay, it was possible in the present study to use somatic cell hybrids to assign the chromosomal location of the tissue factor structural gene (F3) to human chromosome 1 (1pter----1p21).


Cytosolic delivery of granzyme B by bacterial toxins: evidence that endosomal disruption, in addition to transmembrane pore formation, is an important function of perforin.
Granule-mediated cell killing by cytotoxic lymphocytes requires the combined actions of a membranolytic protein, perforin, and granule-associated granzymes, but the mechanism by which they jointly kill cells is poorly understood. We have tested a series of membrane-disruptive agents including bacterial pore-forming toxins and hemolytic complement for their ability to replace perforin in facilitating granzyme B-mediated cell death. As with perforin, low concentrations of streptolysin O and pneumolysin (causing <10% (51)Cr release) permitted granzyme B-dependent apoptosis of Jurkat and Yac-1 cells, but staphylococcal alpha-toxin and complement were ineffective, regardless of concentration. The ensuing nuclear apoptotic damage was caspase dependent and included cleavage of poly(ADP-ribose) polymerase, suggesting a mode of action similar to that of perforin. The plasma membrane lesions formed at low dose by perforin, pneumolysin, and streptolysin did not permit diffusion of fluorescein-labeled proteins as small as 8 kDa into the cell, indicating that large membrane defects are not necessary for granzymes (32 to 65 kDa) to enter the cytosol and induce apoptosis. The endosomolytic toxin, listeriolysin O, also effected granzyme B-mediated cell death at concentrations which produced no appreciable cell membrane damage. Cells pretreated with inhibitors of endosomal trafficking such as brefeldin A took up granzyme B normally but demonstrated seriously impaired nuclear targeting of granzyme B when perforin was also added, indicating that an important role of perforin is to disrupt vesicular protein trafficking. Surprisingly, cells exposed to granzyme B with perforin concentrations that produced nearly maximal (51)Cr release (1,600 U/ml) also underwent apoptosis despite excluding a 8-kDa fluorescein-labeled protein marker. Only at concentrations of >4,000 U/ml were perforin pores demonstrably large enough to account for transmembrane diffusion of granzyme B. We conclude that pore formation may allow granzyme B direct cytosolic access only when perforin is delivered at very high concentrations, while perforin's ability to disrupt endosomal trafficking may be crucial when it is present at lower concentrations or in killing cells that efficiently repair perforin pores.


Synthesis and Evaluation of Some Dibromoquinazoline-sulphonamide Hybrids and some Schiff´s Base Analogs for their Cytotoxic Activity.
Cancer is one of the most dangerous diseases with quite a high mortality rate. Many quinazoline derivatives show potent anticancer activity. In this work our aim is to develop novel, safe and effective anticancer agents. New 6,8-dibromo-2-(4-chlorophenyl)-quinazoline-sulphonamide hybrids and some Schiff´s base analogs were synthesized, and their structures were confirmed by spectral and elemental analysis. Cytotoxicity of all synthesized compounds was evaluated on three cancer cell lines MCF7, HCT116 and HEPG2 using sulpharodamine- B assay method and doxorubicin as a reference drug. All tested compounds show promising cytotoxic activities on the three cell lines. Compound IXd was 2 times more active than doxorubicin on MCF7 cancer cells, while it was 3 times more potent than doxorubicin on HCT116 cancer cells. Compound IV was 2 times more active than doxorubicin while compound VI exhibited similar activity to doxorubicin on HEPG2 cell line. The most active compounds were tested against epidermal growth factor receptor tyrosine kinase (EGFR TK). Compounds IV, IXd, IXf show the most potent inhibitory percent 62.3, 91.1, 91.6 respectively. Compounds IV, V, VII, IXd, IXf caused a significant increase of CASP3 activity with range 86.5-37.6 %. The present work led to the discovery of new cytotoxic compounds having quinazoline pharmacophore.


Impulsivity, sensation-seeking, and part-time job status in relation to substance use and gambling in adolescents.
Although impulsivity, sensation-seeking, and part-time employment have each been linked to risky behaviors in adolescents, their inter-relationships are less well-understood. We examined data from adolescents to assess the following predictions: (1) sensation-seeking would relate closely to substance use and gambling; (2) impulsivity would relate closely to alcohol, drug, and gambling problems; and (3) these relationships would be particularly strong among those holding part-time jobs. High-school students (N = 3,106) were surveyed to provide data on impulsivity, sensation-seeking, and part-time job status. Bivariate and logistic regression analyses were conducted to examine relationships with gambling, substance use (i.e., alcohol, cigarettes, and marijuana) and related problems. Both impulsivity and sensation-seeking related significantly to substance use and impulsivity to gambling. Impulsivity had stronger associations with drug and gambling problems than sensation-seeking did. Students with paid part-time jobs were more likely to drink alcohol, binge drink, and use marijuana. Sensation-seeking had a particularly strong relationship to heavy cigarette smoking among students with part-time jobs. Conversely, there was little relationship between part-time job status and smoking among low sensation-seekers. These findings further support the relevance of sensation-seeking, impulsivity, and part-time job status to risky behaviors among adolescents. Sensation-seeking and impulsivity had unique relationships to risky behaviors, in accordance with theory and prior evidence. Impulsive adolescents may be in particular need for interventions to reduce drug use and gambling. Although part-time jobs can be beneficial, parents and caregivers should be mindful of potential negative ramifications of paid work outside the home.


Development of mobile health-based interventions to promote physical activity in patients with head and neck cancer: a qualitative study.
Despite the well-grounded benefits of physical activity (PA), poor compliance with the PA guidelines has been reported among head and neck cancer (HNC) patients. Mobile health (mHealth)-based interventions can help cancer survivors increase their PA levels and increase the reach or efficiency of rehabilitation services. However, there is limited knowledge about the needs and perceptions of HNC patients regarding these interventions. This study explored the perceptions and needs of HNC patients regarding mHealth-based PA programs before developing such interventions to ensure their improved effectiveness. A constructivist qualitative study. We purposively selected 17 adult HNC patients aged 40-80 years to determine their needs and perceptions of future mHealth-based PA programs. Semi-structured face-to-face interviews were conducted, and the data were analyzed via thematic analysis. The report followed the Consolidated Criteria for Qualitative Research Reports guidelines. Four themes were analyzed from the interview transcripts regarding the needs and perceptions of mHealth-based PA programs: (1) functionality needs; (2) system usage requirements; (3) social support; and (4) perceived barriers and facilitators. HNC patients expect highly customized and specialized mHealth interventions that consider individual factors, address their concerns about security, network, and cost, and prefer improved comfort. Moreover, they expect to receive support from their healthcare providers, families, and peers. The study provides pragmatic ready-to-use recommendations to design interventions for inactive HNC patients to achieve the recommended PA levels. Future mHealth interventions should be tailored according to the needs of the HNC patients by utilizing perceived facilitators and removing perceived barriers to help them engage in PA actively.


CT Findings of Granulomatous Pneumocystis jiroveci Pneumonia in a Patient with Multiple Myeloma.
Although the typical CT findings of Pneumocystis jiroveci pneumonia (PJP) include diffuse or multifocal areas of ground-glass opacities in both lungs, it can also rarely manifest as multiple pulmonary nodules. We report a rare case of atypical PJP in an immunocompromised patient with multiple myeloma, presenting as widespread ground-glass opacities and multiple necrotic subpleural nodules in both lungs on CT, which proved to be granulomatous PJP on percutaneous transthoracic needle biopsy.


MRI of the breast.
MRI of the breast is rapidly evolving as a sensitive technique for the detection and staging of breast cancer. It has considerable benefits but is time consuming and expensive. The benefits and limitations of this technique are presented.


Inferences during story comprehension: cortical recruitment affected by predictability of events and working memory capacity.
Although it has been consistently shown that readers generate bridging inferences during story comprehension, little is currently known about the neural substrates involved when people generate inferences and how these substrates shift with factors that facilitate or impede inferences, such as whether inferences are highly predictable or unpredictable. In the current study, functional magnetic resonance imaging (fMRI) signal increased for highly predictable inferences (relative to events that were previously explicitly stated) bilaterally in both the superior temporal gyri and the inferior frontal gyri. Interestingly, high working memory capacity comprehenders, who are most likely to generate inferences during story comprehension, showed greater signal increases than did low working memory capacity comprehenders in the right superior temporal gyrus and right inferior frontal gyrus. When comprehenders needed to draw unpredictable inferences in a story, fMRI signal increased relative to explicitly stated events in the left inferior gyrus and in the middle frontal gyrus, irrespective of working memory capacity. These results suggest that the predictability of a text (i.e., the causal constraint) and the working memory capacity of the comprehender influence the different neural substrates involved during the generation of bridging inferences.


Thermophysical properties of lithium thiogallate that are important for optical applications.
Lithium thiogallate LiGaS2 is one of the most common nonlinear crystals for mid-IR due to its extreme beam strength and wide transparency range; however, its thermophysical properties have not yet been practically studied. Large crystals of high optical quality are grown. DTA revealed features at 1224 K below melting point (1304 K) that are associated with the oxygen containing compounds of the LiGaO2-x S x type. The thermal conductivity of LiGaS2 (about 10.05 W (m-1 K-1)) and band gap value (3.93 eV at 300 K) are found to be the highest in the LiBC2 family. Isotropic points in the dispersion characteristics for the refractive index are found and LiGaS2-based narrow-band optical filters, smoothly tunable with temperature changes, are demonstrated. Intense blue photoluminescence of anionic vacancies V S is observed at room temperature after annealing LiGaS2 in vacuum, whereas orange low-temperature emission is related to self-trapped excitons. When LiGaS2 crystals are heated, spontaneous luminescence (pyroluminescence) takes place, or thermoluminescence after preliminary UV excitation; the parameters of traps of charge carriers are estimated. The obtained data confirm the high optical stability of this material and open up prospects for the creation of new optical devices based on LiGaS2.


Internal root resorption: a review.
Internal root resorption is the progressive destruction of intraradicular dentin and dentinal tubules along the middle and apical thirds of the canal walls as a result of clastic activities. The prevalence, etiology, pathogenesis, histologic manifestations, differential diagnosis with cone beam computed tomography, and treatment perspectives involved in internal root resorption are reviewed. The majority of the documentation that exists in the literature is in the form of case reports, and there are only a limited number of studies that attempted to examine the histologic manifestations and biologic aspects of the disease. This might be due, in part, to the relatively rare occurrence of this type of resorption and the lack of an in vivo model, apart from the previous attempt on the use of diathermy, to predictably reproduce the condition for study. From a histologic perspective, internal root resorption is manifested in one form that is purely destructive, internal (root canal) inflammatory resorption, and another that is accompanied by repair, internal (root canal) replacement resorption that is featured by the deposition of metaplastic bone/cementum-like tissues adjacent to the sites of resorption. From a differential diagnosis perspective, the advent of cone beam computed tomography has considerably enhanced the clinician's capability of diagnosing internal root resorption. Nevertheless, root canal treatment remains the treatment of choice for this pathologic condition to date.


A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight.
The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure. We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations) and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression. We detected nicotine (80%), cotinine (69%), and trans-3'-hydroxycotinine (57%) in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight. Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.