Towards improved organisational support for nurses working in research roles in the clinical setting: a mixed method investigation.
The clinical research workforce within nursing is growing including those employed to lead studies, coordinate research and many hybrid roles. Several studies have reported high job satisfaction among research nurses. However, there have also been reports of limited options for career development and professional integration, likely reflecting typical informal, departmentally based management models. Institution-wide studies of issues related to research nurses are lacking, thus hampering the design and implementation of effective organisational frameworks to support and develop these positions. To explore experiences of nurses employed in research positions regarding organisational structures and support for research career pathways, and determine what reforms would strengthen an effective research specialisation pathway. A mixed-methods, cross-sectional approach, using a 104-item survey and semistructured interviews of 11 staff in research roles at an acute care hospital in Queensland, Australia. Research nurses lack organisational support in many job aspects that they deem important. A management model for the coordination of research nurses within a health district could maximise development of this field. Academic liaison and mentoring for nurses in research, and recognition for effort, are key areas for a management model to target. Nurses in research roles need individual mentorship, collective support, and the professional recognition and status that researchers in other settings are afforded. A comprehensive research management model would provide structured organisational support for nurses in research, improve professional development opportunities, ensure efficient use of human resources, synergistic working partnerships, and further contribute to a culture of evidence-based healthcare.


Mesoporous and carbon hybrid structures from layered molecular precursors for Li-ion battery application: the case of β-In2S3.
A new method was demonstrated to construct mesoporous and carbon hybrid structures of β-In2S3 from the thermal decomposition of layered molecular precursors. When applied to LIBs, they all exhibit good cycling stability and excellent rate performance due to the great uniformity of mesopores and pyrolysis carbon distributed in the materials.


Characterization of functional excision repair cross-complementation group 1 variants and their association with lung cancer risk and prognosis.
The excision repair cross-complementation group 1 (ERCC1) plays a pivotal role in DNA repair and has been linked to protection against carcinogenesis and resistance to platinum-based anticancer drugs. We tested whether genetic variants in the ERCC1 gene are associated with susceptibility to lung cancer and efficacy of platinum-chemotherapy in patients with small cell lung cancer (SCLC). Thirty individual DNA samples were sequenced to search for single-nucleotide polymorphisms, and the functions of the variants were investigated by a series of biochemical assays. A case-control study was done in 988 patients with lung cancer and 986 control subjects. According to the genotypes, a comparison of chemotherapy outcome in 162 SCLC patients was executed. Overall survival was computed by Cox model adjusted for clinical factors. We identified two functional variants in the ERCC1 5'-flanking region, -433T>C and 262G>T, which cooperatively influence transcriptional regulation of ERCC1. The 262G allele had significantly lower affinity to bind nuclear protein(s) and was associated with decreased ERCC1 RNA expression. The case-control analysis showed that the -433C and 262G alleles are associated with an increased susceptibility to lung cancer, alone and in a gene-smoking joint effect manner. In contrast, the analysis of chemotherapy outcome of SCLC patients revealed that the 262G allele is associated with better drug response and longer survival time compared with the 262T allele. These findings are consistent with the notion that DNA repair is a double-edged sword in cancer and suggest that functional single-nucleotide polymorphisms in ERCC1 might serve as simple and less invasive biomarkers for personalized chemotherapy of platinum-based anticancer drugs.


Numerical evaluation of fractional Tricomi-type model arising from physical problems of gas dynamics.
This paper deals with approximating the time fractional Tricomi-type model in the sense of the Caputo derivative. The model is often adopted for describing the anomalous process of nearly sonic speed gas dynamics. The temporal semi-discretization is computed via a finite difference algorithm, while the spatial discretization is obtained using the local radial basis function in a finite difference mode. The local collocation method approximates the differential operators using a weighted sum of the function values over a local collection of nodes (named stencil) through a radial basis function expansion. This technique considers merely the discretization nodes of each subdomain around the collocation node. This leads to sparse systems and tackles the ill-conditioning produced of global collocation. The theoretical convergence and stability analyses of the proposed time semi-discrete scheme are proved by means of the discrete energy method. Numerical results confirm the accuracy and efficiency of the new approach.


Identification of specific age groups with a high risk for developing cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
The impact of age on the incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a matter of ongoing discussion. The aim of this study was to identify age groups with a higher risk for developing vasospasm, delayed ischemic neurological deficit (DIND), or delayed infarction (DI) and to identify a cut-off age for a better risk stratification. We defined six age groups (<30, 30-39, 40-49, 50-59, 60-69, and >70 years). ROC analysis was performed to determine a cutoff age with the highest positive predictive value (PPV) for developing vasospasm, defined as a blood-flow-velocity-increase >120 cm/s in transcranial-Doppler-sonography (TCD). Multivariate binary-logistic-regression-analysis was then performed to evaluate differences in the incidence of cerebral vasospasm, DIND, and DI among the different age groups. A total of 753 patients were included in the study. The highest incidence (70 %) of TCD-vasospasm was found in patients between 30 and 39 years of age. The cutoff age with the highest PPV (65 %) for developing TCD-vasospasm was 38 years. Multivariate analysis revealed that age <38 years (OR 3.6; CI 95 % 2.1-6.1; p < 0.001) best predicted vasospasm, followed by the need for cerebrospinal fluid drainage (OR 1.5; CI 95 % 1.0-2.3; p = 0.04). However, lower age did not correlate with higher rates of DIND or infarcts. The overall vasospasm-incidence after aSAH is age-dependent and highest in the age group <38 years. Surprisingly, the higher incidence in the younger age group does not translate into a higher rate of DIND/DI. This finding may hint towards age-related biological factors influencing the association between arterial narrowing and cerebral ischemia.


Acute Thyroid Profile Changes During External Beam Irradiation of Neck.
Thyroid gland is irradiated to a considerable dose in conventional radiotherapy of head neck cancer and significant proportion of patients later develop hypothyroidism. This study is an effort to shed light on acute changes in thyroid function after irradiation those are less clearly defined. Values were recorded before radiation treatment, after 4 week of irradiation, after completion of treatment, 1 month after completion of treatment and after 4 months of completion of treatment. A repeated measures ANOVA with a Greenhouse-Geisser correction determined that mean T3, T4 and TSH levels differed statistically significantly between time points. Post hoc test using the Bonferroni correction revealed statistical significance difference in values of T3, T4 and TSH done at specific intervals. External irradiation in cancer therapeutic doses affects thyroid function and sets at a new point with increased TSH, but in reference ranges, to maintain required thyroxin level.


Prevalence of vertebral compression fractures due to osteoporosis in ankylosing spondylitis.
To determine the prevalence of vertebral compression fractures due to osteoporosis in patients with ankylosing spondylitis. Prospective study of 111 consecutive patients; patients with vertebral compression fractures were entered into a case-control study. Outpatient clinic at the centre for rheumatic diseases, Glasgow. 111 Consecutive patients with ankylosing spondylitis. Patients with compression fractures were matched for age and sex with two controls selected from the rest of the group. Patients with biconcave vertebral fractures were also studied. Assessments of spinal deformity and mobility and analysis of lateral radiographs of spines for presence of syndesmophytes. Fifteen patients with compression fractures and five with biconcave fractures were studied. Compared with the controls the patients with compression fractures had increased formation of syndesmophytes in the lumbar spine, whereas those with biconcave fractures had increased formation throughout the spine. Patients with compression fractures also had a greater degree of spinal deformity (distance from wall to tragus 24.5 cm v 12.7 cm in controls), less spinal mobility (20 v 45.6 degrees of flexion), and reduced chest expansion (2 cm v 3cm). Vertebral compression fractures due to osteoporosis are a common but frequently unrecognised complication of ankylosing spondylitis and may contribute to the pathogenesis of spinal deformity and back pain.


Influence of different gases used for laparoscopy (helium, carbon dioxide, room air, xenon) on tumor volume, proliferation, and apoptosis.
Previous reports suggest that helium pneumoperitoneum used for laparoscopic surgery suppresses postoperative tumor growth. The present study was designed to determine the effects of gases used in laparoscopy on tumor volume, proliferation, and apoptosis in rats with implanted malignoma. In 36 rats Morris hepatoma 3294A cells were implanted intrahepatically. Then, after 5 days, they underwent laparoscopy using helium ( n = 7), CO(2) ( n = 7), room air ( n = 7), or xenon ( n = 8). One group received anesthesia only ( n = 7). Rats were killed 10 days after implantation to assess tumor volume, proliferation, and apoptosis. Helium pneumoperitoneum caused a significant smaller tumor volume compared to other groups (Kruskal-Wallis test: p = 0.001; median tumor volume: control: 44 mm3; helium: 19 mm3). There was no significant difference in tumor cell proliferation (PCNA) and apoptosis (TUNEL reaction) between the groups. There was a significant decrease of tumor volume using helium pneumoperitoneum compared to the other gases, but no decreased tumor cell proliferation or increased tumor cell apoptosis.


Follow-up of a sessile juvenile polyp of the colon: a case report.
The aim of this case report is to underline some unusual features of a colonic juvenile polyp found in a young adult: lack of symptoms, site, sessile morphology and increase in site (greater than 50% in 2 years). The usefulness of the radiological survey to indicate endoscopic polypectomy is emphasized.


Constitutive expression of tumor necrosis factor-alpha in cytotoxic cells of teleosts and its role in regulation of cell-mediated cytotoxicity.
Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are the main killer cell populations of the immune system. The mechanisms by which these cells recognize target cells vary considerably, while the effector molecules used to facilitate target cell death are highly conserved. The main pathways utilized by killer cells consist of granule exocytosis and those mediated by members of the TNF superfamily. Nonspecific cytotoxic cells (NCC) are the first identified cytotoxic cell population in teleosts. We have previously demonstrated the expression of granzymes and Fas ligand in these cells. This is the first report of the expression of tumor necrosis factor-alpha in these killer cells. A cDNA coding for TNF was cloned and sequenced from NCC purified from Nile tilapia (Oreochromis niloticus). Factors regulating the transcriptional modulation of TNF in these cells were identified by RT-PCR analysis. The mature form of tilapia TNF was expressed as a recombinant protein and biological activities were analyzed. Using a cross-reacting anti-TNF polyclonal antibody, analysis of TNF expression suggested that tilapia NCC constitutively express the membrane-bound as well as secreted forms of TNF. Recombinant tilapia TNF effectively induced cytotoxicity in the mammalian cell line WEHI, although to a lesser extent compared to the murine TNF. Treatment with recombinant TNF protected NCC from activation-induced cell death. Recombinant tilapia TNF was also effective in upregulation of granzyme transcription in tilapia NCC. These data suggest that teleost TNF may play a role in diverse effector functions of cytotoxic cells from ectotherms, similar to the biological functions described for mammalian TNF.


Age-related changes of cerebral ventricular size. Part II: Normalization of ventricular size following shunting.
Thirty-one hydrocephalic patients were investigated prospectively by means of computed tomographic scan performed prior to and one week after cerebrospinal fluid (CSF) shunting. Planimetric measurements of the size of the cerebral ventricles were compared before and after shunting. Children under two years of age and elderly patients showed significantly less reduction of ventricular size (8.5 +/- 6.3% and 9.7 +/- 3.5% respectively) than older children and young adults (61.2 +/- 5.2%). The degree of reduction of ventricular size did not correlate with pre-operative size of ventricles, duration of disease, or clinical improvement. These findings suggest that reduction of ventricular size following CSF shunting is related to age. We postulate that the size of cerebral ventricles in hydrocephalic patients is not exclusively related to CSF dynamics, but also depends upon the intrinsic elastic properties of the cerebral parenchyma which vary with age.


X-ray diffraction studies of the cross-bridge intermediate states.
Two dimensional x-ray diffraction was obtained from skinned rabbit psoas muscle fibers. The goal is to correlate structures of the cross-bridge population with various intermediate states in the cross-bridge cycle by using nucleotides and their analogs. It was found that in a relaxed muscle in ATP containing solutions, cross-bridges are distributed in three populations in equilibrium: those detached from actin and ordered on the myosin helix, those that are detached and disordered, and those weakly attached to actin in random orientations. The distribution among the three populations is highly dependent on temperature. Those that are detached and yet ordered in a helical structure surrounding the myosin backbone are very likely in the M.ADP.Pi state, supporting an earlier suggestion by Wray (1987). It was also found that the attached cross-bridges with bound MgADP are structurally distinct from those without nucleotide, in agreement with one of our earlier findings by osmotic compression (Xu et al., 1993). Another finding of interest is that the analog AMP-PNP was found to be an ATP analog, rather than an ADP analog as it has been reported previously by many research groups.


Identification of envelope-expanded sentences in normal-hearing and hearing-impaired listeners.
The present study examined the effects of temporal-envelope expansion on speech perception. Sentence identification performance was measured in normal-hearing and hearing-impaired listeners for stationary and fluctuating noise. Two expansion schemes were used to increase the depth of the slow (< 16 Hz) and fast (< 256 Hz) amplitude fluctuations of the stimuli. In the first scheme, the envelope of the stimuli was raised to the power 2. In the second scheme, the high- and low-level segments of the envelope were compressed and expanded, respectively. When envelope processing was applied to speech before the addition of noise, the first form of expansion generally degraded identification, while the second form generally improved identification. When envelope processing was applied to speech after the addition of noise, both forms of expansion improved or did not affect identification scores in both groups of listeners when applied to the slowest fluctuations. When applied to the broadest range of fluctuations, both forms of expansion degraded identification. However, in hearing-impaired listeners, the second form of expansion yielded an increase in performance for fluctuating noise. This complex pattern of results will be discussed in light of previous studies on envelope expansion.


Sprouty gain of function disrupts lens cellular processes and growth by restricting RTK signaling.
Sprouty proteins function as negative regulators of the receptor tyrosine kinase (RTK)-mediated Ras/Raf/MAPK pathway in many varied physiological and developmental processes, inhibiting growth factor-induced cellular proliferation, migration and differentiation. Like other negative regulators, Sprouty proteins are expressed in various organs during development, including the eye; ubiquitously expressed in the optic vesicle, lens pit, optic cup and lens vesicle. Given the synexpression of different antagonists (e.g, Sprouty, Sef, Spred) in the developing lens, to gain a better understanding of their specific role, in particular, their ability to regulate ocular growth factor signaling in lens cells, we characterized transgenic mice overexpressing Sprouty1 or Sprouty2 in the eye. Overexpression of Sprouty in the lens resulted in reduced lens and eye size during ocular morphogenesis, influenced by changes to the lens epithelium, aberrant fiber cell differentiation and compromised de novo maintenance of the lens capsule. Here we demonstrate an important inhibitory role for Sprouty in the regulation of lens cell proliferation and fiber differentiation in situ, potentially through its ability to modulate FGF- (and even EGF-) mediated MAPK/ERK1/2 signaling in lens cells. Whilst growth factor regulation of lens cell proliferation and fiber differentiation are required for orchestrating lens morphogenesis and growth, in turn, antagonists such as Sprouty are just as important for regulating the intracellular signaling pathways driving lens cellular processes.


Identification of self-assembly products from N-phosphoamino acids by electrospray ionization mass spectrometry
The self-assembly products of N-(O,O'-diisopropyl)-L-alpha-amino acids in aqueous media, N-(O,O'-diisopropyl)phosphoryl dipeptides and tripeptides, were identified by electrospray ionization mass spectrometry. A stepwise fragmentation of the [M + H](+) ions from the C-terminus of N-phosphopeptides was observed. Copyright 2000 John Wiley & Sons, Ltd.


Qualitative and quantitative analysis of triterpenoids in different tissues of Pulsatilla chinensis.
Pulsatilla chinensis (P.chinensis) is a traditional Chinese medicine used for the treatment of intestinal amebiasis diseases, vaginal trichomoniasis and bacterial infections. Tritepenoid saponins were important components of P.chinensis. Therefore, we asssessmented expression profiling of triterpenoids in different fresh tissues of P.chinensis by ultra high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and ultra high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS). Firstly, we identified 132 triterpenoids, including 119 triterpenoid saponins, 13 triterpenoid acids and forty seven of them were first determined in Pulsatilla genus, including new aglycones and new ways of rhamnose linking to the aglycone. Secondly, we established the analytical method to analysis triterpenoids content of P.chinensis and comprehensively verified the analytical method by linearity, precision, repeatability, stability and recovery. At last, we quantified 119 triterpenoids simultaneously based on UHPLC-QQQ-MS. The results show that the types and contents of triterpenoids had obvious tissue distribution. New components like rhamnose directly linked to the aglycone mainely distributed in aboveground tissues. Additionally, We identified 15 chemical ingredients as differential components between the aboveground and underground tissues of P.chinensis. This study provides an efficient analysis strategy for the qualitative and quantitative analysis of triterpenoids in P.chinensis even in other traditional Chinese medicines. At the same time, it provides important informations to explain the biosynthetic pathway of triterpenoid saponins in P.chinensis.


Nitrate content and nitrate reductase activity in Rumex obtusifolius L. : II. Responses to nitrate starvation and nitrogen fertilization.
The aim of this work was to investigate the effect of nitrogen starvation and subsequent fentilization with nitrate or ammonium on nitrate content and nitrate reductase activity of Rumex obtusifolius L. under natural conditions.When plants were transplanted to nitrate-poor media, endogenous nitrate was reduced within a few days. In parallel, nitrage reductase activities dropped to about 25% of the initial values. As a consequence of nitrate fertilization (1; 10 or 100 mmol KNO3/l substrate), endogenous nitrate content of the plant abruptly increased within one day. In extreme cases, nitrate concentrations of up to 10% of plant dry weight could be observed without being lethal. High external nitrate concentrations caused an inhibition of nitrate reductase within the leaves, while low external concentrations provoked an increase in the enzyme activity of about 450% within one day. Ammonium fertilization (5 mmol (NH4)2SO4/l substrate) also caused an increase in nitrate reductase activity and nitrate content within leaf blades. This observation indicates a rapid nitrification of ammonium in the substrate. When plants were fertilized with ammonium plus nitrate (2.5 mmol (NH4)2SO4+ 5 mmol KNO3/l substrate), an extremely high and long term increase in nitrate reduction could be observed. Due to an intensive enzymatic nitrate turnover, the nitrate content of leaf blades then remained relatively low. Our observations do not point to an inhibition of nitrate reductase activity in leaves of Rumex obtusifolius by ammonium. Despite temporarily high endogenous nitrate concentrations, Rumex obtusifolius may not be termed as a "nitrate storage" plant, since the accumulation of nitrate is a short term process only.


FXR Inhibits Endoplasmic Reticulum Stress-Induced NLRP3 Inflammasome in Hepatocytes and Ameliorates Liver Injury.
Endoplasmic reticulum (ER) stress is associated with liver injury and fibrosis, and yet the hepatic factors that regulate ER stress-mediated inflammasome activation remain unknown. Here, we report that farnesoid X receptor (FXR) activation inhibits ER stress-induced NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes. In patients with hepatitis B virus (HBV)-associated hepatic failure or non-alcoholic fatty liver disease, and in mice with liver injury, FXR levels in the liver inversely correlated with the extent of NLRP3 inflammasome activation. Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. FXR attenuates CCAAT-enhancer-binding protein homologous protein (CHOP)-dependent NLRP3 overexpression by inhibiting ER stress-mediated protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation. Our findings implicate miR-186 and its target, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), in mediating the inhibition of ER stress by FXR. This study provides the insights on how FXR regulation of ER stress ameliorates hepatocyte death and liver injury and on the molecular basis of NLRP3 inflammasome activation.


Manifestation of neuronal ceroid lipofuscinosis in Australian Merino sheep: observations on altered behaviour and growth.
Neuronal ceroid lipofuscinoses (NCL) is an inherited neurodegenerative disorder in children. Presently there is no effective treatment and the disorder is lethal. NCL occur in a variety of non-human species including sheep, which are recognised as valuable large animal models for NCL. This experiment investigated the progressive postural, behavioural and liveweight changes in NCL-affected lambs, to establish practical, non-invasive biomarkers of disease progression for future preclinical trials in a CLN6 Merino sheep model. A flock of eight lambs at pasture was studied, with the observer blind to the disorder status. Three genotypes were compared: homozygous affected NCL; n = 4), clinically normal heterozygous (Carrier; n = 2) and homozygous normal (non-carrier control (Normal); n = 2). Direct observation during daylight and continuous accelerometer measurements over 72 h were used to quantify lamb posture and behaviour in 11 sessions between 26-60 weeks of age, conducted at 3-5 week intervals. There was a Genotype (G) × Age (A) interaction (P = 0.001) for liveweight of the lambs in the experiment, with NCL, Carrier and Normal lambs gaining 11.8, 16.5 and 23.4 kg, respectively, between 26 and 60 weeks of age. G×A interactions were also found for walking behaviour (means for NCL, Carrier and Normal genotype groups at 26 and 60 weeks, were 1.7 and 7.9%, 3.3 and 3.1%, and 2.5 and 1.9% of observations, P = 0.008) and a composite variable of key behaviours identified in the principal components analysis (P < 0.001), with mean values for NCL lambs increasing three-fold compared to non-affected lambs as age increased. Similarly, NCL lambs became less responsive to visual and auditory stimuli as they aged. Mean responsiveness scores (out of 3) to visual stimuli for the NCL, Carrier and Normal genotypes at 26 and 60 weeks of age were 2.7 and 1.4, 2.8 and 2.9, and 3.0 and 3.0, respectively (G × A, P < 0.001). Changes in response to auditory stimuli were similar to visual stimuli. NCL lambs took more (P = 0.015) steps per 24 h than Carrier and Normal genotype lambs, but there was no G × A interaction. At 26 and 60 weeks of age respectively, NCL lambs took 2724 and 4121 steps per 24 h, compared to Carrier (1708 and 3105 steps) and Normal genotype lambs (2109 and 3506 steps). NCL lambs also performed less (P = 0.018) grazing behaviour than Carrier and Normal genotype lambs (66.5, 72.3 and 72.5% of observations for NCL, Carrier and Normal lambs, respectively). A number of behavioural changes identified in the experiment could form the basis for a protocol for monitoring and evaluation of disease progression.


Synthesis and biological evaluation of novel sinomenine derivatives as anti-inflammatory and analgesic agent.
Sinomenine (SIN) has long been known as an anti-inflammatory drug, while poor efficiency and large-dose treatment had limited its further application. A series of novel SIN derivatives 1-26 were designed and synthesized to improve its anti-inflammatory activity. The anti-inflammatory activity evaluation showed most of the derivatives exhibited enhanced anti-inflammatory activity in vitro compared to SIN. Compound 17 significantly inhibited LPS-induced secretion of pro-inflammatory factors NO (IC50 = 30.28 ± 1.70 μM), and suppressed the expression of iNOS, IL-6 and TNF-α in RAW264.7 cells. Moreover, compound 17 showed excellent anti-inflammatory in mouse paw edema. Immunohistochemistry results revealed that compound 17 exerted anti-inflammatory activity by inhibiting the pro-inflammatory cytokine TNF-α. Furthermore, compound 17 exhibited an analgesic effect in vivo. The results attained in this study indicated that compound 17 had the potential to be developed into an anti-inflammation and analgesic agent.


Auditory brain-stem response and temperature: relationship in the guinea pig.
The neurological applications of the auditory brain-stem response depend largely on the stability of the interval between the peaks of waves I and V. Using guinea pigs, it was demonstrated that hyperthermia and small temperature changes, as well as hypothermia, may affect interpeak latency (IPL) sufficiently to affect its clinical interpretation. The relationship between temperature and IPL is specified by a power function such that there is a 5.3% increase in IPL for a 1 degree C drop. Although the constant for humans may differ from that of guinea pigs, the results of this animal study demonstrate that the relationship between temperature and IPL is invariant from 27 degrees C to 40 degrees C.


Ciliated differentiation of rabbit tracheal epithelial cells in vitro.
Primary cultures of rabbit tracheal epithelial (RbTE) cells have been performed in two different ways. Quantitative analysis of both proliferative capacities and ciliated differentiation process were carried out using epithelial cell cultures from tracheal explants and from dissociated tracheal epithelial cells in air-liquid interface conditions. We show that both alpha- and beta-tubulins from RbTE cells are polyglutamylated and that this posttranslational modification is restricted to cilia axonemes and centrioles of non-ciliated cells. A monoclonal antibody raised against polyglutamylated tubulins was used to quantify the proportion of ciliated cells. Even though epithelial cells from outgrowths obtained by the explant technique highly proliferated during the first days of culture, no ciliated differentiation occurred. On the other hand, using air-liquid interface conditions after proliferation of dissociated cells, we could observe and quantify a ciliated cell differentiation in vitro by both Western blot and flow cytometric analysis. The specific detection and quantification of ciliated cells open the way for the biochemical and molecular characterization of centriolar components during ciliated differentiation.


Chromatographic evaluation of sorption and diffusion characteristics of glucose, maltose and maltotriose in silica gels.
Liquid chromatographic techniques were employed to evaluate the sorption and diffusion characteristics of glucose, maltose and maltotriose in silica gel. The equilibrium constants were found to decrease with increasing molecular size. The determined diffusion coefficient of glucose is comparable to that in the literature. The pore diffusivities decrease with increasing size of the carbohydrates at all temperatures.


Formation and temperature stability of G-quadruplex structures studied by electronic and vibrational circular dichroism spectroscopy combined with ab initio calculations.
Variations in the structure of d(GGGA)(5) oligonucleotide in the presence of Li(+), Na(+), and K(+) ions and its temperature stability were studied using electronic and vibrational circular dichroism, IR absorption, and ab initio calculations with the Becke 3-Lee-Yang-Parr functional at the 6-31G** level. The samples were characterized by nondenaturing gel electrophoresis. Oligonucleotide d(GGGA)(5) in the presence of Li(+) forms a nonplanar single tetramer, with angles of 102 degrees and 171 degrees between neighboring guanine bases. This tetramer changes its geometry at temperatures >50 degrees C, but does not form a quadruplex structure. In the presence of Na(+), the d(GGGA)(5) structure was optimized to almost planar tetramers with an angle of 177 degrees between neighboring guanines. The spectral results suggest that it stacks into a quadruplex helical structure. This quadruplex structure decayed to a single tetramer at temperatures >60 degrees C. The Hartree-Fock energies imply that d(GGGA)(5) prefers to form complexes with Na(+) rather than Li(+). The d(GGGA)(5) structure in the presence of monovalent ions is stabilized against thermal denaturation in the order Li(+) < Na(+) < K(+).


Thoracoscopic Lung Suffusion.
The lung is a common site of metastatic disease, which may be the only measurable malignancy in some patients. Unfortunately, because of the invasiveness of previous techniques and the fragility of these target organs, many attempts at regional lung therapies have not become that popular. Accordingly, a method for thoracoscopic vascular control to enable permeation of the lung with agents was developed and termed suffusion to distinguish it from earlier methods. This article describes the preclinical work supporting lung suffusion and our early human experience.


Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs.
Due to the growing demand of enantiomerically pure compounds, as well as the increasing strict safety, quality and environmentally requirements of industrial synthetic processes, the development of more sustainable, healthy and economically attractive strategies for the synthesis of chiral biologically active molecules is still an open challenge in the pharmaceutical industry. In this context, the biotransformations field has emerged as a real alternative to traditional synthetic routes, because of the exquisite chemo-, regio- and enantioselectivities commonly displayed by enzymes; thus, biocatalysis is becoming a widespread methodology for the synthesis of chiral compounds, not only at laboratory scale, but also at industrial scale. As hydrolases and oxido-reductases are the most employed enzymes, this review is focused on describing several industrial processes based on the use of these enzymes for obtaining chiral compounds useful for the pharmaceutical industry.


Evaluation of risk factors for unanticipated hospital admission following ambulatory surgery - An observational study.
Unanticipated admissions following ambulatory surgery significantly affect hospital admission and operation room flow. Most of the factors responsible for unanticipated admission following ambulatory surgery were preventable. It is, therefore, crucial to improve patient selection criteria and to identify the risk factors for unanticipated admission during preoperative period. These unanticipated admissions have now been considered as quality care indicator and a target to improve healthcare costs. To assess the reasons and risk factors for unanticipated hospital admission after ambulatory surgery. Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia. In this case-control study, cases who were re-admitted within 48 hours following ambulatory surgery were included. The convenience sampling was used to identify controls. Data including patients' demographics, type of anesthesia and surgery, any intraoperative or postoperative complications, etc., were extracted. Descriptive statistics is used to summarize the study variables. Mean and standard deviation were used for quantitative variables. Percentage and frequencies were used for qualitative variables. Univariate and multivariate logistic regressions were used to assess risk factors for unanticipated hospital admission after ambulatory surgery. There were 153 cases and 147 controls in this study. The study found postoperative pain as the most common reason for re-admission after ambulatory surgery followed by bleeding, fever, and asthma exacerbation. Multivariate logistic regression showed age, BMI more than 40, and presence of respiratory disease as risk factors (P < 0.05). Age, high BMI more than 40, and presence of respiratory disease increase the risk of unanticipated hospital admission after ambulatory surgery.


Recommendations of the AGG (Working Group for Obstetrics, Department of Maternal Diseases) on How to Treat Thyroid Function Disorders in Pregnancy.
Objective These recommendations from the AGG (Committee for Obstetrics, Department of Maternal Diseases) on how to treat thyroid function disorder during pregnancy aim to improve the diagnosis and management of thyroid anomalies during pregnancy. Methods Based on the current literature, the task force members have developed the following recommendations and statements. These recommendations were adopted after a consensus by the members of the working group. Recommendations The following manuscript gives an insight into physiological and pathophysiological thyroid changes during pregnancy, recommendations for clinical and subclinical hypo- and hyperthyroidism, as well as fetal and neonatal diagnostic and management strategies.


Community knowledge and practice of malaria prevention in Ghindae, Eritrea, a Cross-sectional study.
Little is known about community knowledge and practice towards malaria prevention in Ghindae, Eritrea. A community based cross-sectional study design was employed among 380 households. Participants were selected systematically. More than eight-tenth (86.5%) of the respondents had heard information about malaria preceding the survey; health facilities (54.1%), television (23.7%). Majority (94.2%) mentioned mosquito bite as the main mode of malaria transmission. Fever was the predominantly (89.2%) identified sign/symptoms of malaria. ITN (84.4%) and environmental sanitation (67.3%) were well recognized preventive measures for malaria. Though most households (91%) possess bed nets, but only 37% were ragged on observation. Overall, 64% of the respondents have satisfactory knowledge and 57.3% had adequate practice towards malaria prevention. Malaria knowledge was significantly associated with increased age (p=0.001) and district areas (p=0.022). Malaria prevention practice was significantly associated with Tigrigna and Saho ethnic group (p=0.013), and districts (p=0.02). Districts showed significant difference with an OR=4.56 (95%CI, 1.29-16.09) on knowledge for district 04 and OR=1.98(95%-CI, 1.21-3.26) on practice for district 03 compared to district 01. Knowledge was associated with prevention (OR=1.99, 95%CI, 1.28-3.09). Overall community knowledge and practice towards malaria prevention were satisfactory. Furthermore, comprehensive community interventions are paramount for effective sustainable control.


USP7: Structure, substrate specificity, and inhibition.
Turnover of cellular proteins is regulated by Ubiquitin Proteasome System (UPS). Components of this pathway, including the proteasome, ubiquitinating enzymes and deubiquitinating enzymes, are highly specialized and tightly regulated. In this mini-review we focus on the de-ubiquitinating enzyme USP7, and summarize latest advances in understanding its structure, substrate specificity and relevance to human cancers. There is increasing interest in UPS components as targets for cancer therapy and here we also overview the recent progress in the development of small molecule inhibitors that target USP7.


QRS fragmentation as a possible electrocardiographic diagnostic marker in patients with acute myocarditis: preliminary histopathological validation.
We aim to assess the reproducibility of QRS fragmentation (fQRS) on a multi-centre dataset of patients with acute myocarditis (AM), including a histopathological validation in a subgroup with biopsy-proven disease. Electrocardiogram (ECG) in patients with myocarditis is usually considered aspecific. ST changes and conduction anomalies have been commonly reported so far. We have previously described fQRS in patients with AM. Patients admitted between 2008 and 2019 in two centres with a diagnosis of AM were included. Standard ECG, echocardiography, and cardiac magnetic resonance (CMR) findings were recorded at baseline and at follow-up (FU). Eighty patients were analysed, 66 men (82%), with median age of 34 (26-43) years. Twenty-two patients had biopsy-proven AM. At presentation, 61 patients (76%) displayed fQRS. Median ejection fraction (EF) was 55% (43-60). Seventy-two patients (90%) underwent CMR and displayed late gadolinium enhancement (LGE). ECG leads showed that fQRS correlated with distribution of LGE. In patients with positive biopsy, fQRS was present in 18 (81%). Median FU was 419 days (224-956). Complete FU was available for 64 patients (80%), and 33 patients (52%) displayed persistence of fQRS. Median EF was 60% (57-64). Eleven patients underwent a repeated biopsy at FU, eight of whom had persistent inflammation and fQRS. Fifteen patients (23%) had ventricular tachycardia, 14 of whom still showed fQRS. In this cohort fQRS was confirmed as an additional useful ECG sign. Persistence of fQRS was associated with ongoing inflammation and with a poorer outcome in terms of ventricular function and occurrence of arrhythmias.


A qualitative investigation of body weight and weight loss-related attitudes of mothers and fathers in the context of food insecurity.
To examine attitudes about body weight and weight loss among low-income parents of young children experiencing household food insecurity. One-on-one interviews were conducted with 25 dyads of cohabitating low-income mothers and fathers who lived with their child aged 2.5-10 years old. Basic inductive analysis was conducted using NVivo to identify emerging themes related to body weight. Three main themes emerged including (1) weight loss as a "Blessing in Disguise," (2) trouble with losing weight, and (3) the impact of compromised diet quality. Some differences existed in themes between mothers and fathers, but both placed value on weight loss resulting from food insecurity. This research underscores the importance of sufficient nutrition assistance for limited resource families. A lack of money for food was a barrier towards maintaining a healthy weight but the value our culture places on weight loss even in times of despair was undeniably present. Level V, cross-sectional descriptive study.


Plate tectonics of the Red Sea and East Africa.
The relative motion between the plates on each side of the East African Rift Valley can be obtained from the opening of the Red Sea and the Gulf of Aden. The calculated direction of relative motion agrees well with fault plane solutions for earthquakes north of the equator.


Experimental design considerations for verifying the performance of screening technologies for dioxin and dioxin-like compounds in soils and sediments.
A performance verification demonstration of technologies capable of detecting dioxin and dioxin-like compounds in soil and sediment samples was conducted in April 2004 under the US Environmental Protection Agency's Superfund Innovative Technology Evaluation (SITE) Monitoring and Measurement Technology (MMT) Program. A demonstration plan was developed with input from the participating technology developers who were part of an advisory panel convened to provide technical guidance for this test. The development of the experimental design began with the framework traditionally used for testing field analytical monitoring technologies under the SITE MMT Program, but various unique aspects of the participating technologies and the expected applications for these technologies necessitated modification of several elements of the traditional design. These critical experimental design considerations are described in this manuscript, along with issues encountered and the remedies that were developed. A summary of the performance data for each technology tested is also presented.


Weight Loss Interventions for Rehabilitation Patients with Obesity.
This scoping review aims to explore the contributions of rehabilitation interventions and programs to the management of obesity. Studies and review papers describing weight management for patients in rehabilitation programs were identified. Rehabilitation populations for which weight loss interventions were reported included spinal cord injury, osteoarthritis, cardiac, and psychiatric. Evidence exists to support the promotion of weight loss in patients with obesity receiving rehabilitation services. Outcomes associated with weight loss in obese rehabilitation patients include reduced pain, improved mobility, improved performance of activities of daily living, increased self-efficacy for stair climbing and walking and, increased participation in leisure activities. Despite the prevalence of obesity among groups of patients with physical and psychiatric disabilities and the evidence to support weight loss as beneficial to improve function more research is needed to determine the best way in which to provide weight loss interventions to groups of patients with neurological, musculoskeletal, and psychiatric disabilities. Research is needed to gain knowledge about discipline specific interventions and their impact on obesity management in rehabilitation populations.


Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses.
LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2(-/-)) mice. LRRK2(-/-) mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2(-/-) mice. LRRK2(-/-) mice had a significantly higher serum IgA level, and TNP-Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells.


18F-sodium fluoride positron emission tomography (NaF-18-PET/CT) radiomic signatures to evaluate responses to alpha-particle Radium-223 dichloride therapy in osteosarcoma metastases.
Patients with osteoblastic metastases from high risk osteosarcoma continue to have a poor prognosis after progression from standard-of-care multi-agent chemotherapy. In a first-in-human dose escalation trial of bone targeted Radium 223 dichloride alpha-particle therapy in 18 patients with advanced osteosarcoma only 1 patient responded based on conventional Response Evaluation Criteria in Solid Tumors (RECIST). Na18F PET response Criteria in Solid Tumors(NAFCIST), based on Sodium fluoride-18 (Na18F) positron emission tomography (PET)-CT was developed to better evaluate bone specific response. To further appreciate the spatial and temporal heterogeneity of the partial or mixed responses, a radiomics method was developed. Analyses were performed with 18F-sodium fluoride positron emission tomography imaging studies before and after alpha-particle therapy. Radioactive 18F- -atom concentrations were measured in soft-tissues, in approximately 1000 concentration data points for 18F- per 1 cm3 metastatic tumor. Data was analyzed from the SUV intensity values, the histogram of intensities and entropy values. Radiomics may inform intra-tumoral and inter-tumoral heterogeneity in response of bone forming osteosarcoma to alpha particle therapy. Each patient (and each tumor) represents an "N of 1" case and warrants in depth analysis individually.


Learning the landscape: implementation challenges of primary care innovators around cancer survivorship care.
This study describes the experiences of early implementers of primary care-focused cancer survivorship delivery models. Snowball sampling was used to identify innovators. Twelve participants (five cancer survivorship primary care innovators and seven content experts) attended a working conference focused on cancer survivorship population strategies and primary care transformation. Data included meeting discussion transcripts/field notes, transcribed in-depth innovator interviews, and innovators' summaries of care models. We used a multistep immersion/crystallization analytic approach, guided by a primary care organizational change model. Innovative practice models included: (1) a consultative model in a primary care setting; (2) a primary care physician (PCP)-led, blended consultative/panel-based model in an oncology setting; (3) an oncology nurse navigator in a primary care practice; and (4) two subspecialty models where PCPs in a general medical practice dedicated part of their patient panel to cancer survivors. Implementation challenges included (1) lack of key stakeholder buy-in; (2) practice resources allocated to competing (non-survivorship) change efforts; and (3) competition with higher priority initiatives incentivized by payers. Cancer survivorship delivery models are potentially feasible in primary care; however, significant barriers to widespread implementation exist. Implementation efforts would benefit from increasing the awareness and potential value-add of primary care-focused strategies to address survivors' needs. Current models of primary care-based cancer survivorship care may not be sustainable. Innovative strategies to provide quality care to this growing population of survivors need to be developed and integrated into primary care settings.


Induced production of rabbit articular cartilage-derived chondrocyte collagen II on polyhydroxyalkanoate blends.
Three-dimensional porous scaffolds made from blend polyesters of polyhydroxyalkanoates (PHA) were evaluated with respect to their effects on collagen II production. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay collagen II mRNA for evaluation of the ability for the blend scaffolds to induce collagen II production. It was found that scaffold of poly-3-hydroxybutyrate (PHB) blended with a copolyester consisting of 3-hydoxybutyrate-co3-hydroxyhexanate (PHBHHx) in a radio of 1:2 had strong ability to induce collagen II production compared with other ratios of PHB/PHBHHx and poly-L-lactic acid (PLA). Collagen II expression level remained approx. 1.5-times higher on the above-mentioned blend compared with that of PLA throughout four weeks cultivation. At the same time, the PHB/PHBHHx blend (1:2) exhibited a similar tendency as PLA to maintain the collagen 11 expression level over the entire culture period. The results showed that the PHB/PHBHHx blend (1:2) reported to improve mechanical properties compared with PHB or PHBHHx improved biocompatibility in comparison with PHB, PHBHHx, PLA and other blending systems consisting of PHB/PHBHHX in ratios of 2:1 and 1:1, respectively.


Reduction of ascorbate free radical by the plasma membrane of synaptic terminals from rat brain.
Synaptic plasma membranes (SPMV) decrease the steady state ascorbate free radical (AFR) concentration of 1mM ascorbate in phosphate/EDTA buffer (pH 7), due to AFR recycling by redox coupling between ascorbate and the ubiquinone content of these membranes. In the presence of NADH, but not NADPH, SPMV catalyse a rapid recycling of AFR which further lower the AFR concentration below 0.05 microM. These results correlate with the nearly 10-fold higher NADH oxidase over NADPH oxidase activity of SPMV. SPMV has NADH-dependent coenzyme Q reductase activity. In the presence of ascorbate the stimulation of the NADH oxidase activity of SPMV by coenzyme Q(1) and cytochrome c can be accounted for by the increase of the AFR concentration generated by the redox pairs ascorbate/coenzyme Q(1) and ascorbate/cytochrome c. The NADH:AFR reductase activity makes a major contribution to the NADH oxidase activity of SPMV and decreases the steady-state AFR concentration well below the micromolar concentration range.


Phylogenetically informative rearrangements in mitochondrial genomes of Coleoptera, and monophyly of aquatic elateriform beetles (Dryopoidea).
Mitochondrial gene order in Coleoptera has been thought to be conservative but a survey of 60 complete or nearly complete genomes revealed a total of seven different gene rearrangements (deletions, gene order reversals), mainly affecting tRNA genes. All of these were found to be limited to a single taxon or a subclade of Coleoptera. The phylogenetic distribution of a translocation of tRNA(Pro) in three species of elateriform beetles was investigated further by sequencing three nearly complete mitochondrial genomes (Dascillidae, Byrrhidae, Limnichidae) and ten additional individuals for a ∼1370 bp diagnostic fragment spanning the relevant region. Phylogenetic analysis consistently recovered the monophyly of families previously grouped in the contentious superfamily Dryopoidea, a group of approximately 10 beetle families with mainly aquatic lifestyles. The Byrrhidae (moss beetles) were not part of this lineage, although they may be its sister group, to recover the widely accepted Byrrhoidea. The tRNA(Pro) translocation was present in all members of Dryopoidea, but not in any other Elateriformia, providing independent support for this lineage and for a single origin of aquatic habits.


Anti-β2 glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via two receptors: apolipoprotein E receptor 2' and glycoprotein I bα.
Anti-β2 glycoprotein I (anti-β2GPI ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β2GPI antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti- β2GPI antibodies in complexes with β2GPI as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I ba) in platelet activation induced by the anti-β2GPI /β2GPI complex. The interaction between the anti-β2GPI /β2GPI complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GPII b/III a activation and P-selectin expression and thromboxane B2 production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β2GPI /β2GPI complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β2GPI /β2GPI complex induced platelet activation via GPI ba and apoER2', which may then contribute to the prothrombotic tendency in APS patients.


Monomeric and dimeric conformation of the vinculin tail five-helix bundle in solution studied by EPR spectroscopy.
The cytoskeletal adaptor protein vinculin plays an important role in the control of cell adhesion and migration, linking the actin cytoskeleton to adhesion receptor complexes in cell adhesion sites. The conformation of the vinculin tail dimer, which is crucial for protein function, was analyzed using site-directed spin labeling in electron paramagnetic resonance spectroscopy. Interspin distances for a set of six singly and four doubly spin-labeled mutants of the tail domain of vinculin were determined and used as constraints for modeling of the vinculin tail dimer. A comparison of the results obtained by molecular dynamic simulations and a rotamer library approach reveals that the crystal structure of the vinculin tail monomer is essentially preserved in aqueous solution. The orientation of monomers within the dimer observed previously by x-ray crystallography agrees with the solution electron paramagnetic resonance data. Furthermore, the distance between positions 1033 is shown to increase by >3 nm upon interaction of the vinculin tail domain with F-actin.


An event-related potential investigation of distanced self-talk: Replication and comparison to detached reappraisal.
Emotion regulation is critical for managing stress, but many regulatory strategies consume high levels of cognitive resources to implement, which are depleted under stress. This raises a conundrum: the tools we have to feel better may be ineffective when they are most needed. Recent event-related potential (ERP) research indicates that distanced self-talk (i.e., reflecting on one's experiences using non-first-person singular pronouns and one's name) reduces negative emotional reactivity without overtaxing cognitive resources. Here, we report the first direct replication of this work and extend it by examining how distanced self-talk compares to detached reappraisal, one of the most frequently studied regulatory techniques. Sixty-seven participants were randomly assigned to an emotion regulation picture task and instructed to reflect on the feelings they experienced in response to viewing negative emotional images using distanced self-talk or detached reappraisal while ERPs were measured. Directly replicating past findings, distanced self-talk led to a reduction in an affective arousal ERP, the late positive potential (LPP), without increasing stimulus preceding negativity (SPN), an ERP that reflects anticipatory and preparatory processing. These results further bolster support for distanced self-talk as a relatively effortless emotion regulation strategy. On the other hand, detached reappraisal was neither associated with the modulation of the LPP nor the SPN. Due to the failed replication of the reappraisal effect, a direct comparison between emotion regulation strategies was not conducted. Methodological limitations that may have contributed to the reappraisal failure and future directions for comparisons between emotion regulation strategies are discussed.


Bright Organic Mechanoluminescence and Remarkable Mechanofluorochromism from Circularly Polarized TADF Enantiomers with Aggregation-Induced Emission Properties.
The development of circularly polarized thermally activated delayed fluorescence (CP-TADF) luminogens with stimuli-response characteristics remains challenging. Herein, a pair of organic enantiomers, S-CzTA and R-CzTA, with aggregation-induced emission properties, have been successfully developed by introducing chiral 1,2,3,4-tetrahydronaphthalene and carbazole to phthalimide. They present CP-TADF properties in toluene solutions, giving dissymmetric factors of 0.84×10-3 and -1.03×10-3 , respectively. In the crystalline state, both S-CzTA and R-CzTA can emit intense blue TADF and produce very bright sky-blue mechanoluminescence (ML) and remarkable mechanofluorochromism (MFC) under the stimuli of mechanical force. Single-crystal analysis and theoretical calculation results suggest that their ML activities are probably associated with their chiral and polar molecular structures and unique non-centrosymmetric molecular packing modes. Furthermore, the MFC properties of the enantiomers likely originate from the destruction of crystal structure, leading to the planarization of molecular conformation. This work may provide helpful guidance for developing new CP-TADF materials with force-stimuli-responsive properties.


A new quinolinone-chalcone hybrid with potential antibacterial and herbicidal properties using in silico approaches.
Quinolinone-chalcones are hybrid compounds consisting of chalcone and quinolone moieties with biological activity related to their hybrid structure. This work seeks to describe the structural and theoretical parameters related to the physicochemical properties and biological activity of a new quinolinone-chalcone. The synthesis, structural characterization by X-ray diffraction, molecular topology by Hirshfeld surfaces and QTAIM, molecular electronic calculations, and pharmacophore analysis were described. The weak interactions C-H…O, C-H…π, and C-H…Br were responsible for crystal growth and stabilized the crystalline state. The DFT analysis shows that the sulfonamide group region is susceptible to observed interactions, and the frontier molecular orbitals indicate high kinetic stability. Also, pharmacophore analysis revealed potential antibacterial and herbicidal activity; by docking within the active site of TtgR, a transcription regulator for the efflux pump TtgABC from the highly resistant Pseudomonas putida (P. putida) strain DOT-TIE, we showed that the activation of TtgR relies upon the binding of aromatic-harboring compounds, which plays a crucial role in bacterial evasion. In this context, a new quinolinone-chalcone has a higher binding affinity than tetracycline, which suggests it might be a better effector for TtgR.


Three-dimensional reconstruction of trachea using computed tomography imaging as therapy for tracheal stenosis in infants.
In this study, we aim to develop a system that uses computed tomography (CT) imaging for three-dimensional (3D) reconstruction of the trachea as therapy for tracheal stenosis in infants, and further calculate the cross-sectional area and volume, assisting doctors in clinical diagnosis. We first used image processing, calculating the cross-sectional area and volume. We used the improved median filter for image processing and designed the system for capturing the cross-sectional area of endotracheal tube. We then established 3D reconstruction images with isosurface extraction technology and calculated the cross-sectional area and volume. Medical indicator data analysis was performed. The median filter developed in this study performed better in filtering speckle noise compared to traditional filtering methods. Furthermore, the median filter can keep fine texture feature, so that the subsequent contour selection and 3D reconstructed volume are more accurate. We also proposed new medical grading indexes according to tracheal obstruction volume ratio to assist doctors with the diagnosis and provide recommendations on treatment. Seventeen samples were examined in this study. Four sections of each sample are reviewed. Sixty-eight sections were used for validation, and the overall accuracy is very reliable. Using image processing we obtained tracheal CT images before 3D reconstruction and calculated the cross-sectional area and volume of the trachea. New medical indicators are proposed according to the location and severity of stenosis to assist doctors with diagnosis.


Significance of prostate cancer missed on needle biopsy tools for retrieving missed cancer.
Prostate needle biopsy (PNB) is required for the diagnosis of prostate cancer (PCa), but little is known about the frequency and clinical implication of false-negative results. To investigate the incidence and clinical impact of minute PCa missed on routine haematoxylin and eosin (H&E) slides, but retrieved by α-methylacyl-CoA-racemase (AMACR) immunohistochemistry. AMACR immunohistochemistry was used to detect PCa missed on H&E slides in a series of consecutive 1,672 PNB including 1,003 patients without evidence of PCa, and 669 patients with PCa meeting pathological criteria for active surveillance (PCAS) under current clinical investigation, including Gleason score ≤7 (3 + 4), <33% of biopsies involved by cancer, <50% of any core involved by cancer. Using improved multicore (pre-) embedding techniques a single AMACR immunostain/patient was sufficient to detect missed lesions. In patients without histological evidence of PCa, AMACR immunohistochemistry retrieved minute PCa in 33 of 1,003 patients (3.29%) and atypical small acinar proliferations (ASAP) in 17 of 1,003 patients (1.69%). Among 116 of 669 (17.34%) PCa patients meeting PCAS, detection of additional core(s) involved by cancer was found responsible for disease reclassification in 63 of 116 of patients (54.31%). Limitations include the single-institutional design of the study. PCa missed on routine H&E histology was retrieved by AMACR in 8.91% of PNB, including 17.34% of PCa patients meeting PCAS. 54.31% of them have finally lost their eligibility for active surveillance after detecting additional cores involved by cancer. Underdiagnosis of limited adenocarcinoma on PNB is a matter of concern, but can be prevented by a single AMACR immunostain/patient if improved multicore (pre-) embedding techniques are used.


Emotional learning promotes perceptual predictions by remodeling stimulus representation in visual cortex.
Emotions exert powerful effects on perception and memory, notably by modulating activity in sensory cortices so as to capture attention. Here, we examine whether emotional significance acquired by a visual stimulus can also change its cortical representation by linking neuronal populations coding for different memorized versions of the same stimulus, a mechanism that would facilitate recognition across different appearances. Using fMRI, we show that after pairing a given face with threat through conditioning, viewing this face activates the representation of another viewpoint of the same person, which itself was never conditioned, leading to robust repetition-priming across viewpoints in the ventral visual stream (including medial fusiform, lateral occipital, and anterior temporal cortex). We also observed a functional-anatomical segregation for coding view-invariant and view-specific identity information. These results indicate emotional signals may induce plasticity of stimulus representations in visual cortex, serving to generate new sensory predictions about different appearances of threat-associated stimuli.


Optical Loupes: A Useful Tool for the Oncall Otorhinolaryngologist-Our Experience.
We aimed to evaluate the efficacy and utility of loupes for ENT on-calls. We conducted a 2 month prospective clinical study using loupes during on-calls. We examined patients twice, with and without loupes and compared visibility and diagnostic ease. We used the loupes in a total of 71 patients for a variety of ENT emergencies. We found that visibility and diagnostic ease was improved in all cases. During procedures we found that improved visibility led to better instrument placement and more satisfactory outcomes. Loupes have been previously used intra-operatively with good results. The obstacles to wider usage are reportedly the expense and learning curve required. We have acquired some cheap loupes and have found evidence that earlier usage eases the transition. We have found that they are a useful addition to the on-call ENT armoury as they facilitate superior visibility and improved instrument placement.


Biochemical studies with infectious bursal disease virus: comparison of some of its properties with infectious pancreatic necrosis virus.
Infectious bursal disease (IBD) virus was purified from the bursae of infected chickens. Two morphologically indistinguishable populations of virus particles were separated in sucrose gradients and possessed sedimentation coefficients of 295S and 460S. Both populations contained RNA and had identical polypeptide compositions. IBD virus banded at a density of 1.31 g/ml in CsCl and at 1.24 g/ml in sodium potassium tartrate. IBD virus contained two RNA segments with mol. wts. of 2.4X10(6) and 2.2X10(6) as estimated by polyacrylamide-agarose gel electrophoresis, but sedimented in sucrose gradients at 15S. Virus RNA was resistant to 0.1 micrograms/ml ribonuclease treatment under conditions in which ribosomal RNA was completely hydrolysed, but was sensitive to 1.0 and 10 micrograms/ml treatments. These results suggest that the RNA consists of either double-stranded or highly ordered single-stranded molecules. IBD virus contained seven polypeptides with mol. wts. in the range 97,000 to 24,000. Two polypeptides were absent in empty particles of IBD virus. IBD and infectious pancreatic necrosis (IPN) viruses were morphologically indistinguishable. IPN virus possessed a sedimentation coefficient of 440S and banded at a density of 1.32 g/ml in CsCl. In addition the electrophoretic mobilities of IBD and IPN virus RNAs were almost identical. Polyacrylamide slab gel electrophoresis showed that while the number and size of the polypeptides were different for each virus there were similarities in the overall pattern.


Eighteen-year anamnesis of osteoid osteoma--a diagnostic problem?
The 18-year history of osteoid osteoma in a woman aged 43 is presented. The typical physical and radiographic findings are described. Total removal of the tumor resulted in prompt and permanent relief of symptoms. Diagnosis, histopathology, differential diagnosis, treatment, and prognosis of the tumor are discussed.


Ruth Beutler: the woman behind Karl von Frisch.
The Journal of Comparative Physiology A was founded in 1924 as the Zeitschrift für vergleichende Physiologie by Karl von Frisch and Alfred Kühn. Given the marginalization of women in science at that time, it is remarkable that the first article in the Journal was authored by a female scientist, Ruth Beutler. Throughout her scientific career, she was affiliated with the Zoological Institute of the University of Munich, which, under the leadership of von Frisch, evolved into a world-class academic institution. Despite chronic health problems, Beutler was one of the first women who succeeded in obtaining the Habilitation as qualification for appointment to a professorial position. She was also one of the first scientists who applied methods from physiological chemistry to the study of zoological phenomena. Yet, for many years she was employed as a technician only, and she was never appointed to an Ordinarius (tenured full professorship) position. Her most important contributions to comparative physiology outside her own area of research were her support for, and protection of, Karl von Frisch, particularly during the Nazi era when he, as a 'quarter-Jew,' faced imminent threat of forced retirement; and after World War II, when her efforts as interim Ordinarius were instrumental in re-building the bombed-out Zoological Institute to persuade Karl von Frisch to return to Munich. It was also one of her observations that prompted him to revisit, and revise, his earlier (incorrect) model of how honeybees communicate, through their dances, the direction and distances of food sources from the hive.


Risk factors for onset and persistence of psychosis.
Clinical practice, training and evaluation of treatment in the functional psychoses continues to be carried out mostly along the traditional line of separation by diagnostic entity. However, the combined evidence from research on risk factors for onset and for persistence of psychotic illness indicates quantitative, but not qualitative, differences between categories of schizophrenia and affective psychosis. "Developmental" factors, such as childhood dysfunction, increased cerebral ventricle size and familial morbid risk of schizophrenia operate preferentially, though not specifically, at that end of the psychopathological spectrum characterised by a preponderance of negative features. On the other hand, "social" factors, such as ethnic group, adverse life events and familial morbid risk of affective disorder have a larger impact at the end associated with predominance of affective features. Heterogeneity in the functional psychoses may thus be best conceived as two discrete effects operating at different ends of a continuous psychopathological spectrum. The use of highly reliable but arbitrary diagnostic categories may introduce serious bias in aetiological and treatment research. Evidence supporting the validity of a model of shared risk factors for continuous characteristics needs to be further elaborated and incorporated into our concepts of psychotic illness.


Temperature effect on cable force of a special-shaped tied-arch bridge.
In this study, on-site monitoring was used to obtain the temperature field distribution and cable force values of the bridge at various times, the temperature change pattern of the bridge elements, the temperature sensitivity of the cable force of different parts of the bridge, and the trend of the cable force under temperature load were all analyzed. The static response of the wires was studied under various operating circumstances. The total cable force of the bridge is inversely related to the temperature rise and fall, and the temperature sensitivity of the cable force in different parts of the bridge is different under the same temperature effect. The change in cable force is uneven. They vary according to the loading circumstances. This project's cable force changes are the most substantial and consistent with observed circumstances and should be appropriately considered in comparable projects. Thermal impacts must be addressed in strand cable safety design.


The matrix (M) protein of vesicular stomatitis virus regulates transcription.
Temperature-sensitive mutants of vesicular stomatitis virus (VSV) belonging to complementation group III contain a lesion in the matrix (M) protein. This results in a 2--5 fold increase in transcription at the nonpermissive temperature. Co-infection of cells with one of these mutants and wild-type virus reverses this mutant phenotype. Separation of the transcriptional and translational products from mutant-infected cells reveals an overall increase in each of the viral mRNA species concomitant with degradation of the M protein at the nonpermissive temperature. The increase in mRNA, however, does not lead to increased synthesis of viral proteins. Quantitation of individual mRNA species indicates that M protein acts as a direct inhibitor of transcription as well as an attenuator of sequential transcription.


Analysis of Veno-Venous Extracorporeal Membrane Oxygenation for COVID-19 Compared to Non-COVID Etiologies.
This study analyzed the characteristics and outcomes of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to COVID-19 versus non-COVID causes at US academic centers. V-V ECMO support has been utilized for COVID-19 patients with ARDS since the beginning of the pandemic. Mortality for ECMO in COVID-19 has been reported to be high but similar to reported mortality for ECMO support for non-COVID causes of respiratory failure. Using ICD-10 codes, data of patients who underwent V-V ECMO for COVID-19 ARDS were compared with patients who underwent V-V ECMO for non-COVID causes between April 2020 and December 2022. The primary outcome was in-hospital mortality. Secondary outcome measures included length of stay and direct cost. Multivariate logistic regression modeling was performed to analyze differences in mortality between COVID and non-COVID groups, adjusting for other important risk factors (age, sex, and race/ethnicity). We identified and compared 6382 patients who underwent V-V ECMO for non-COVID causes to 6040 patients who underwent V-V ECMO for COVID-19. There was a significantly higher proportion of patients aged ≥ 65 years who underwent V-V ECMO in the non-COVID group compared with the COVID group (19.8% vs. 3.7%, respectively, P <0.001). Compared with patients who underwent V-V ECMO for non-COVID causes, patients who underwent V-V ECMO for COVID had increased in-hospital mortality (47.6% vs. 34.5%, P <0.001), length of stay (46.5±41.1 days vs. 40.6±46.1, P <0.001), and direct hospitalization cost ($207,022±$208,842 vs. $198,508±205,510, P =0.02). Compared with the non-COVID group, the adjusted odds ratio (OR) for in-hospital mortality in the COVID group was 2.03 (95% CI: 1.87-2.20, P <0.001). In-hospital mortality for V-V ECMO in COVID-19 improved during the study time period (50.3% in 2020, 48.6% in 2021, and 37.3% in 2022). However, there was a precipitous drop in the ECMO case volume for COVID starting in quarter 2 of 2022. In this nationwide analysis, COVID-19 patients with ARDS requiring V-V ECMO support had increased mortality compared with patients who underwent V-V ECMO for non-COVID etiologies.


High prevalence of food intolerances among US internet users.
Food intolerances are commonly reported and are predicted to have gastrointestinal health implications. We aimed to quantify the prevalence of food intolerances among US adults and identify culprit foods through a brief web-based survey. We invited participation in an online cross-sectional survey involving a single questionnaire. Data were summarised using percentages or medians and interquartile range. Participant characteristics by self-reported food intolerance were compared using the Wilcoxon rank sum test and Pearson's χ2 test. Adjusted analyses were performed using multivariable logistic regression. The survey was internet-based via Amazon's mechanical Turk, a crowdsourcing website for the completion of requester directed tasks. Adults who were US-based internet users were invited at ages 18-80. We collected 2133 survey responses (ages 18-79 years). The rate of food intolerance was 24·8 % (95 % CI 23·0, 26·6) in US adults. Younger (P < 0·01), female (P = 0·05) and Asian, African American or multiple race individuals (P < 0·01) predominated. Lactose intolerance was most common. Frequency of a non-lactose food intolerance was 18·1 % (95 % CI 16·5, 19·8). When categorised broadly, grains, fruit, lactose, fish, vegetables, alcohol and nuts were most troublesome for individuals in that order. Self-reported food intolerance is common in US internet users. The effect of food on gastrointestinal symptoms and avoidant behaviours deserves further attention.


Effect of acclimation temperature on oxygen transport in the blood of the carp, Cyprinus carpio.
The temperature dependence of the O2 equilibrium in whole blood was measured in carp acclimated for more than 3 weeks at 10 degrees C or 20 degrees C water temperature. O2 combining curves were obtained for the same samples at 10 degrees C or 20 degrees C using blood from the 10 degrees C or 20 degrees C acclimated fish (group A) or only at the acclimation temperature (group B). Whereas in group B the P50 was about the same at both temperatures, in group A P50 was higher at 20 degrees C than at 10 degrees C, yielding an apparent heat of oxygenation delta H = -9.9 kcal/mol at pH = 8.0. The CO2 Bohr effect in group A was delta log P50/delta pH = -0.93 at 20 degrees C and -1.17 at 10 degrees C, whereas in group B no temperature effect was seen (-0.98 and -0.97). The acclimation temperature had no effect on the electrophoretic Hb pattern. As expected, the in vivo pH changed inversely with temperature from 8.06 at 10 degrees C to 7.73 at 20 degrees C, enhancing the temperature-induced shift in P50. Acclimation reverses partly the changes in O2 affinity, thereby improving the uptake of oxygen in the gills.


Peripheral modulation of mechano-sensitivity in primary afferent neurons.
Considerable attention has centered recently on the changes in neuron excitability and synaptic efficacy caused by certain biogenic amines and neuropeptides. These neuromodulators act at a wide variety of both central and peripheral targets, and bring about diverse biological results. In sensory pathways, modulation occurs at central input synapses of the primary afferents and at peripheral terminals of efferents. This study was undertaken to look at non-synaptic modulation of membrane potentials in peripheral sensory endings of identifiable receptors. Using intracellular recording from the three primary afferent fibres of a recently described simple crustacean stretch receptor, which lacks centrifugal control, we observed in vitro modulation of the sensory response by three neuroactive substances known to be present in vivo. Two neuroamines, serotonin and octopamine, depressed receptor potentials and impulse discharge whereas the pentapeptide proctolin enhanced both these components of the sensory response. The peripheral sensory modulation reported here for a lobster mechano-receptor may occur in many animal groups and sensory systems.


New procedure for extraction of algal lipids from wet biomass: a green clean and scalable process.
A new procedure, called Simultaneous Distillation and Extraction Process (SDEP), for lipid extraction from wet microalgae (Nannochloropsis oculata and Dunaliella salina) was reported. This method does not require a pre-drying of the biomass and employs alternative solvents such as d-limonene, α-pinene and p-cymene. This procedure has been compared with Soxhlet extraction (Sox) and Bligh & Dyer method (B&D). For N. oculata, results showed that SDEP-cymene provided similar lipid yields to B&D (21.45% and 23.78%), while SDEP-limonene and pinene provided lower yields (18.73% and 18.75% respectively). For D. salina, SDEP-pinene provided the maximum lipid yield (3.29%) compared to the other solvents, which is quite close to B&D result (4.03%). No significant differences in terms of distribution of lipid classes and fatty acid composition have been obtained for different techniques. Evaluation of energy consumption indicates a substantial saving in the extraction cost by SDEP compared to the conventional extraction technique, Soxhlet.


Analysis of ground reaction forces by means of wavelet transform.
To identify details of clinical relevance in ground reaction forces by means of wavelet transform. A retrospective analysis of gait tests performed by total knee replacement patients and a control population has been performed. The ground reaction forces have been processed by means of wavelet transform. Results of the wavelet analysis are represented, in a time-frequency plane, by tiles. These are coloured in different grey levels associated to the values of a suitable energy function of the expansion coefficients, resulting from the wavelet transform. The high frequency tiles revealed the presence of irregularities with clinical significance in the first part of the stance phase. These transients in ground reaction forces are described in a quantitative manner allowing to monitor their evolution during the patient observation time. The heel strike transient has been identified by the tile representation of the vertical component of ground reaction forces and confirmed by its correlation with corresponding irregularities in the other components. The tile representation allows to detect and to quantify details not easily perceivable by the examiner through traditional techniques. The wavelet transform seems particularly appealing for clinical applications such as outcome assessment or treatment evaluation and can assist in the definition of normative models of ground reaction forces. The effectiveness of the procedure suggest to try to automate it. The tile representation allows to identify and to keep the records of ground reaction forces clinically significant details, such as heel strike transient.


Retained knife blade and acute superior vena cava obstruction.
A case is described in which transfixation of the superior vena cava by the retained blade of a knife was the cause of acute caval obstruction. Use of a venous cannula as a stent allowed repair of the caval lacerations.


Therapeutic stereotactic procedures on the thalamus for motor movement disorders.
The value of functional neurosurgery in the treatment of motor movement disorders is emphasized. The two methods of stereotactic procedures, namely a destructive one with small lesions centered on specific targets, and a non-destructive one with chronically inserted electrodes connected with an also implanted programmable neuropacemaker are described in detail. The results in Parkinsonian tremor, essential tremor, tremor of multiple sclerosis, post-traumatic tremor and in other involuntary movement disorders are reported and demonstrate that stereotactic neurosurgical treatment of these conditions is a safe and efficacious method.


[Methods for simultaneous recording of pharmacodynamic and toxic effects on interior sensitive receptors, respiration and cardiac-circulatory system of guinea pigs (author's transl)].
A method for simultaneous, continuous registration of pharmacodynamic and toxic effects, resp., on pulmonary-stretch receptors, on respiration and on hemodynamics in guinea pigs is described. The following parameters are recorded synchronously by a multi-track recorder: 1. The afferences in the cervical n. vagus; its electrical integration is employed for measuring the total intensity and the ex- and the inhalation intensity, resp., of the afferences; 2. the pneumatogram for measuring the maximum velocity of air flow, duration of the breath phase and parts thereof (in-, and exhalation and postexpiratory pause), and the respiration rate; 3. the diastolic and systolic blood pressure during in- and exhalation and postexpiratory pause; 4. the electrocardiogram (ECG). The normal distribution of the initial values is examined and discussed. Further the initial values measured in three series of experiments are discussed and compared: mono-vagotomy/spontaneous respiration, bivagotomy/spontaneous respiration and artificial respiration/monovagotomy. The results are compared with some experimental and clinical findings from literature.


Multimodal sex-related differences in infant and in infant-directed maternal behaviors during months three through twelve of development.
Using the concepts of sensory and affective experience, this work relates the concepts of socialization and cognitive development to the embodiment of gender in the human infant. Evidence obtained from biweekly observations from 30 children and their mothers observed from age 3 months to age 12 months revealed measurable sex-related differences in how mothers handle and touch their infants. This work offers novel approaches to visualizing combinations of behaviors with the aim of encouraging researchers to think in terms of suites of action rather than singular sensory or motor systems. New avenues of research into the mechanisms which produce sex-related differences in behavior are suggested.


Twenty Years of the Ryan Residency Training Program in Abortion and Family Planning.
To summarize the effects of routine, opt-out abortion and family planning residency training on obstetrics and gynecology (ob-gyn) residents' clinical skills in uterine evacuation and intentions to provide abortion care after residency. Data from ob-gyn residency programs supported during the first 20 years of the Kenneth J. Ryan Residency Training Program in Abortion and Family Planning were analyzed. Postrotation surveys assessed residents' training experiences and acquisition of abortion care skills. Residency program director surveys assessed benefits of the training to residents and the academic department from the educators' perspectives. A total of 2775 residents in 89 ob-gyn programs completed postrotation surveys for a response rate of 72%. During the rotation, residents - including those who only partially participated - gained exposure to and skills in first- and second-trimester abortion care. Sixty-one percent intended to provide abortion care in their postresidency practice. More than 90% of residency program directors (97.5% response rate) reported that training improved resident competence in abortion and contraception care and 81.3% reported that the training increased their own program's appeal to residency applicants. Over 20 years, the Ryan Program has supported programs to integrate abortion training to give ob-gyn residents the skills and inspiration to provide comprehensive reproductive health care, including uterine evacuation and abortion care, in future practice. Residency program directors noted that this integrated training meets resident applicants' expectations. Ryan Program residents are trained to competence and are prepared, both clinically and in their professional attitudes, to care for women's reproductive health.


Aryl C-glycosides: physiologically stable glycomimetics of sialyl Lewis X.
In the course of the search for physiologically stable, structurally simple, and low molecular weight sLeX mimetics, aryl C-glycosides with carboxylic acid functionality 2 were found to be extremely potent inhibitors against L- and P-selectins with IC50 in the low microM range.


Non-canonical programmed cell death mechanisms triggered by natural compounds.
Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis-related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction.


Influence of contextual cues on the choice reaction time of mildly retarded adults.
Nonretarded and mildly retarded subjects were compared on an 8-choice reaction-time (RT) task. Removing a midline that divided the stimulus display in halves slowed RTs of retarded subjects to stimuli adjacent to the line. In the absence of this line, retarded subjects were also much more dependent upon the position of the preceding stimulus and response.


Safety and efficacy of Vitamin D3 supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial.
The study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D3 supplementation in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP). The secondary objective was to assess the effects of vitamin D3 on complete haematological response (CHR) and its safety. Double-blind, placebo-controlled, exploratory randomised trial. Tertiary care hospital in northern India. Treatment-naive patients with chronic phase chronic myeloid leukaemia (n=62) aged >12 years were recruited from January 2020 to January 2021. Patients with progressive disease, pregnancy and hypercalcaemia were excluded. Oral vitamin D3 supplementation (60 000 IU) or matched placebo was given once weekly for an initial 8 weeks along with imatinib after randomisation with 1:1 allocation ratio. The primary outcome was to compare EMR (defined as BCR-ABL1 transcript level ≤10%, international scale) at 3 months. The secondary outcomes were to compare effect of the intervention on CHR, correlation of 25(OH)2D3 levels with treatment response and safety according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. At baseline, 14.5% of the patients had normal vitamin D3 levels. EMR at 3 months was attained in 24 patients (82.7%) of the vitamin D3 group and 21 (75%) of the placebo group (OR 1.6, 95% CI 0.37 to 7.37, p=0.4). A significant difference in vitamin D3 levels from baseline to the end of study was observed. Patients with vitamin D3 supplementation did not achieve higher CHR in comparison with placebo (OR 1.3, 95% CI 0.25 to 7.23, p=1.0). Vitamin D3 levels were not significantly correlated with BCR-ABL1 levels. No dose-limiting toxicities were observed. Vitamin D3 levels were low among patients with CML-CP in this study. Vitamin D3 supplementation with imatinib therapy did not have significant effect on EMR or CHR. Further clinical trials could be undertaken to assess the effective dosage and duration of vitamin D3 supplementation in these patients. CTRI/2019/09/021164.


Torsion of a wandering spleen treated with partial splenectomy and splenopexy.
Wandering spleen is a rare and unusual entity, characterized by excessive mobility and displacement of the organ from its normal position. This happens due to congenital or acquired anomalies leading to the lack of the spleen's suspensory ligaments. Clinical presentation is variable; acute abdominal pain may occur when persistent torsion of the splenic pedicle results in splenic infarction. Ultrasonography, computed tomography, and magnetic resonance imaging are modalities that may be used in diagnosis. The treatment of choice is surgery, with splenectomy or splenopexy, the latter being preferred. The patient was a 38-year-old woman with a 10-day history of left-sided abdominal pain. Imaging demonstrated a wandering spleen with partial infarction of the inferior pole. An open partial splenectomy with splenopexy of the remaining spleen was performed with the use of an absorbable mesh sutured to the abdominal wall and stomach. Her recovery was uneventful and on follow-up she had no signs of recurrence or complications. Wandering spleen should be considered in cases of acute abdominal pain, and surgery is the treatment of choice, with the goal of preservation of the organ whenever possible.


Biocompatibility Studies of Gadolinium Complexes with Iminodiacetic Acid Derivatives.
Apart from using as radiopharmaceuticals, iminodiacetic acid derivatives, after complexation with gadolinium, have been also tested as MRI CAs (magnetic resonance imaging contrast agents) since they show high affinity to hepatocytes and therefore provide high-resolution MRI of the liver. The purpose of this study was to evaluate the biocompatibility of four gadolinium complexes with iminodiacetic acid (IDA) derivatives differing in substituent in aromatic ring by estimating their influence on plasma hemostasis, integrity of erythrocyte membrane, and toxicity towards human umbilical vein endothelial cells (HUVECs). The influence of gadolinium-based CAs on plasma hemostasis was evaluated by measuring PT (prothrombin time), APTT (activated partial tromboplastin time), and TT (thrombin time). The effects of tested compounds on RBCs (Red Blood Cells) were assessed using hemolysis assay and microscopy studies. The influence of gadolinium complexes on the barrier properties of HUVECs was assessed by means of real-time method based on the measurements of the impedance changes of the cells. Gadolinium complexes did not affect significantly PT and TT. APTT measurements revealed significant prolongation in the presence of all tested gadolinium complexes at the concentration higher than 0.5 μmol/mL. Hemolysis assay showed that compounds with alkyl substituents in benzene ring without halogen atom (1-3) do not exert unfavorable effect on the integrity of erythrocyte membrane over the entire concentration range. All gadolinium complexes at 1.0 μmol/mL contribute to the decrease in HUVEC viability and integrity. To conclude, the study describes biocompatibility studies of gadolinium-based CAs, provides additional insight into their potential toxicity associated with systemic administration, and underscores the necessity for further research.


RIBER/DIBER: a software suite for crystal content analysis in the studies of protein-nucleic acid complexes.
Co-crystallization experiments of proteins with nucleic acids do not guarantee that both components are present in the crystal. We have previously developed DIBER to predict crystal content when protein and DNA are present in the crystallization mix. Here, we present RIBER, which should be used when protein and RNA are in the crystallization drop. The combined RIBER/DIBER suite builds on machine learning techniques to make reliable, quantitative predictions of crystal content for non-expert users and high-throughput crystallography.