Mortimer Frank, Johann Ludwig Choulant, and the history of anatomical illustration.
Mortimer Frank (1874-1919) was an ophthalmologist in Chicago, Illinois. He published a number of papers on the history of medicine, and was secretary of the Chicago Society of the History of Medicine and editor of their Bulletin. His major contribution to the history of medicine relates to the history of anatomical illustration. The classic book on that subject had been published in 1852 in German by the physician and historian, Johann Ludwig Choulant (1791-1861). However, by Frank's time this text was both out dated and out of print. Frank took on the tremendous project of translating Choulant's German text into English as History and Bibliography of Anatomic Illustration in Its Relation to Anatomic Science and The Graphic Arts. He improved Choulant's text with the results of his and other scholars' research, greatly enlarging the text. Frank supplemented the original book with a biography of Choulant, essays on anatomists not considered in the original text, and an essay on the history of anatomical illustration prior to those authors discussed by Choulant. This book, now referred to as Choulant/Frank, has been reprinted several times, and is still useful as a reference in this field, though some of its research is now dated.


Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the "bivalent" Sea Snake Antivenom.
Recent advances in proteomics enable deep profiling of the compositional details of snake venoms for improved understanding on envenomation pathophysiology and immunological neutralization. In this study, the venom of Australian tiger snake (Notechis scutatus) was trypsin-digested in solution and subjected to nano-ESI-LCMS/MS. Applying a relative quantitative proteomic approach, the findings revealed a proteome comprising 42 toxin subtypes clustered into 12 protein families. Phospholipases A2 constitute the most abundant toxins (74.5% of total venom proteins) followed by Kunitz serine protease inhibitors (6.9%), snake venom serine proteases (5.9%), alpha-neurotoxins (5.6%) and several toxins of lower abundance. The proteome correlates with N. scutatus envenoming effects including pre-synaptic and post-synaptic neurotoxicity and consumptive coagulopathy. The venom is highly lethal in mice (intravenous median lethal dose=0.09μg/g). BioCSL Sea Snake Antivenom, raised against the venoms of beaked sea snake (Hydrophis schistosus) and N. scutatus (added for enhanced immunogenicity), neutralized the lethal effect of N. scutatus venom (potency=2.95mg/ml) much more effectively than the targeted H.schistosus venom (potency=0.48mg/ml). The combined venom immunogen may have improved the neutralization against phospholipases A2 which are abundant in both venoms, but not short-neurotoxins which are predominant only in H. schistosus venom. A shotgun proteomic approach adopted in this study revealed the compositional details of the venom of common tiger snake from Australia, Notechis scutatus. The proteomic findings provided additional information on the relative abundances of toxins and the detection of proteins of minor expression unreported previously. The potent lethal effect of the venom was neutralized by bioCSL Sea Snake Antivenom, an anticipated finding due to the fact that the Sea Snake Antivenom is actually bivalent in nature, being raised against a mix of venoms of the beaked sea snake (Hydrophis schistosus) and N. scutatus. However, it is surprising to note that bioCSL Sea Snake Antivenom neutralized N. scutatus venom much more effectively compared to the targeted sea snake venom by a marked difference in potency of approximately 6-fold. This phenomenon may be explained by the main difference in the proteomes of the two venoms, where H. schistosus venom is dominated by short-neurotoxins in high abundance - this is a poorly immunogenic toxin group that has been increasingly recognized in the venoms of a few cobras. Further investigations should be directed toward strategies to improve the neutralization of short-neurotoxins, in line with the envisioned production of an effective pan-regional elapid antivenom.


Biomechanical load during patient transfer with assistive devices: Cross-sectional study.
This study utilised a cross-sectional design to perform measurements of muscle activity as well as forward - and lateral trunk inclination angle during a full workday among 52 female healthcare workers from 16 different departments at five Danish hospitals. Using linear mixed models, the 95th percentile ranks of the normalised root mean square (nRMS) values were analysed for the different types of assistive devices. Compared to no assistive device (mean nRMS 27.9%, 95% CI 24.8%-31.0%), the use of intelligent beds (23.9%, CI 20.2%-27.6%) and ceiling-lifts (24.0%, CI 20.3%-27.7%) led to lower erector spinae nRMS values across all types of patient transfers. Conversely, the use of bedsheets (30.6%, CI 27.1%-34.2%), sliding-sheets (30.3%, CI 26.8%-33.9%) and sliding-boards (33.5%, CI 29.5%-37.6%) were associated with higher levels of erector spinae muscle activity.Consistent use of ceiling-lifts and intelligent beds reduces the physical workload and may thereby decrease the risk of musculoskeletal disorders among healthcare workers. Practioner Summary: Frequent patient transfer is associated with an increased risk of back pain and injury among healthcare workers. This analysis compares the level of physical load during patient transfer with commonly used assistive devices. The results show that use of the ceiling-lift and intelligent bed is associated with relatively low physical load during patient transfer. Abbreviations: RMS: root mean square; nRMS: normalized root mean square; EMG: electromyography; MSD: musculoskeletal disorder; LBP: low-back pain; VAS: visual analogue scale; MVC: maximal voluntary contraction.


Management of Cooley's anaemia.
The current management of Cooley's anaemia has succeeded in prolonging the patient's life to at least the fourth decade, in allowing a number of the patients to procreate children, and in allowing most of them to lead a nearly unrestricted normal life. The price to be paid for this is the cumbersome and expensive adherence to a rigorous regimen of chronic transfusion and compliance with chelation therapy. Economical and psychological factors make it difficult for many patients to benefit from these advances, but those who can may be reasonably assured of a long and fruitful existence. It must be realized that the only defect in Cooley's anaemia is one of haemoglobin synthesis, and well-managed patients are in any other aspect capable of leading a normal life. In certain areas of the world, such as Cyprus (Loukopoulos et al, 1990) and Sardinia (Cao et al, 1990), extensive and intensive programmes of prenatal screening have reduced to nearly negligible levels the birth of children with Cooley's anaemia (see Chapter 9 this volume). Yet, in many countries a complete management of Cooley's anaemia is today not feasible for economic or cultural reasons, and this disease remains a serious public health problem. The future of the management of Cooley's anaemia appears at the moment full of hopes and frustrations (Gale, 1989; Bank, 1990). However, it is important to understand that if the current group of patients with Cooley's anaemia have to be the beneficiaries of future developments (be it genetic engineering and/or advances in histocompatibility matching), it is necessary that these patients be maintained in excellent clinical shape. It would be very sad when a cure for Cooley's anaemia became available, if most patients could not avail themselves of it because of pre-existing irreversible body damage.


On becoming a surgeon.
A dentist who has just completed eight years of oral and maxillofacial residency training reflects on what drew him to the specialty and how it changed him. He notes three characteristics of his training that differed from predoctoral education and help define a surgeon: patient-based learning, learning from constant discussions with colleagues, and the habit of facing unexpected outcomes as a source of learning.


Synthesis of murine leukemia virus plus strong stop DNA initiates at a unique site.
The 5'-terminal segment of plus strong stop DNA has been isolated from an endogenous virion reverse transcription reaction and characterized. The plus strong stop DNA is shown to initiate with the sequence 5'AATGAAAGA.... The 5'-terminal nucleotide is a deoxyribonucleotide. No residual protein or RNA moiety was found attached to the plus strong stop DNA. Thus, the mechanism which primes plus strand synthesis is still unclear. No evidence for multiple initiation sites or heterogeneous starts is observed. This data indicates that the initiation of plus strong stop DNA synthesis by the virion RNA-dependent DNA polymerase is a precise event which occurs at a unique site on the retrovirus genome.


Coexistence of stable and unstable population dynamics in a nonlinear non-Hermitian mechanical dimer.
Non-Hermitian two-site dimers serve as minimal models in which to explore the interplay of gain and loss in dynamical systems. In this paper, we experimentally and theoretically investigate the dynamics of non-Hermitian dimer models with nonreciprocal hoppings between the two sites. We investigate two types of non-Hermitian couplings; one is when asymmetric hoppings are externally introduced, and the other is when the nonreciprocal hoppings depend on the population imbalance between the two sites, thus introducing the non-Hermiticity in a dynamical manner. We engineer the models in our synthetic mechanical setup comprised of two classical harmonic oscillators coupled by measurement-based feedback. For fixed nonreciprocal hoppings, we observe that, when the strength of these hoppings is increased, there is an expected transition from a PT-symmetric regime, where oscillations in the population are stable and bounded, to a PT-broken regime, where the oscillations are unstable and the population grows/decays exponentially. However, when the non-Hermiticity is dynamically introduced, we also find a third intermediate regime in which these two behaviors coexist, meaning that we can tune from stable to unstable population dynamics by simply changing the initial phase difference between the two sites. As we explain, this behavior can be understood by theoretically exploring the emergent fixed points of a related dimer model in which the nonreciprocal hoppings depend on the normalized population imbalance. Our study opens the way for the future exploration of non-Hermitian dynamics and exotic lattice models in synthetic mechanical networks.


Roles of GABAergic inhibition for the binaural processing of multiple sound sources in the inferior colliculus.
This review explores the questions of how spike trains that originate from lower auditory nuclei interact in the inferior colliculus to produce an output that synthesizes the information from all these sources. The focus is on the processing of interaural intensity disparities, the cues animals use to localize high-frequency sounds, and the roles of the lateral superior olives and the dorsal nucleus of the lateral lemniscus (DNLL) in shaping the binaural properties of their targets in the inferior colliculus. The main points advanced in this review are 1) that the DNLL shapes the binaural properties of many inferior collicular neurons, 2) that the inhibitory inputs to the DNLL allow it to act as a switch that can be turned on or off with appropriate acoustic stimulation, and 3) that when two or more stimuli are presented, each from a different region of space, the first stimulus can switch the DNLL to its off position. The consequence of the initial stimulus is that stimuli that follow shortly thereafter cannot activate the DNLL, and thus the binaural properties of those collicular cells that receive inhibition from the DNLL are changed. The implications of this switching action are that the location of the initial signal is coded appropriately, whereas the coding of the location of the signal or signals that follow the initial signal is smeared, and consequently, those following signals cannot be accurately localized. In short, it is proposed that the DNLL plays a pivotal role in the way the locations of multiple sound sources are coded by the auditory system.


Structural basis for map formation in the thalamocortical pathway of the barrelless mouse.
Barrelless mice (BRL) homozygous for the BRL mutation that disrupts the gene coding for adenylyl cyclase type I on chromosome 11 lack spatial segregation of layer IV cortical cells and of the thalamocortical axons (TCAs) into barrel domains. Despite these morphological perturbations, a functional topographic map has been demonstrated. We reconstructed individual biocytin-injected TCAs from thalamus to barrel cortex in NOR (normal) and BRL mice to analyze to what extent the TCA arborization pattern and bouton distribution could explain the topographic representation of the whisker follicles. In BRL, the geometry of TCA is modified within layer IV as well as in infragranular layers. However, in both strains, the spatial distribution of TCA in layer IV reflects the spatial relationship of their cell bodies in the ventrobasal nucleus of the thalamus. The morphometric analysis revealed that TCAs of both strains have the same length, branch number, and number of axonal boutons in layer IV. However, in barrelless, the boutons are distributed within a larger tangential extent. Analysis of the distribution of boutons from neighboring thalamic neurons demonstrated the existence in layer IV of domains of high bouton density that in both strains equal the size and shape of individual barrels. We propose that the domains of high bouton density are at the basis of the whisker map in barrelless mice.


Backbone dynamics of a highly disordered 131 residue fragment of staphylococcal nuclease.
In order to characterize the dynamic properties of the denatured state of staphylococcal nuclease, R1, R2, and NOE relaxation parameters have been measured for the backbone 15N nuclei of a 131 residue fragment that serves as a model of the denatured state under non-denaturing conditions. The relaxation data indicate a wide range of amplitudes for segmental motion and are inconsistent with a random coil conformation. An optimal value of 7.8 ns was obtained for the molecular rotational correlation time tau m based on the analysis of the 79 residues for which R1, R2, and NOE relaxation data could be obtained. This value corresponds roughly to the slowest detectable motion on the nanosecond time scale and is of a magnitude consistent with global tumbling of a large portion of the molecule. For the majority of residues, experimental data could be described most adequately in terms of a modified "model-free" formalism which includes contributions from internal motions on both an intermediate (tau e) and a fast time scale (tau f) in the context of slow overall tumbling (tau m). The generalized order parameters S2, which gives the amplitude of motions on time scales faster than tau m, correlates with sequence hydrophobicity and suggests a relationship between chain flexibility and sequence propensity for hydrophobic collapse. The fractional populations of three alpha-helices in the protein show a stronger correlation with S2 values and hydrophobicities than with intrinsic helix propensities. These observations suggest that secondary structure may be preferentially stabilized in hydrophobic segments of the sequence.


Simple Non-Equilibrium Atmospheric Plasma Post-Treatment Strategy for Surface Coating of Digital Light Processed 3D-Printed Vanillin-Based Schiff-Base Thermosets.
A simple non-equilibrium atmospheric plasma post-treatment strategy was developed for the surface coating of three-dimensional (3D) structures produced by digital light processing 3D printing. The influence of non-equilibrium atmospheric plasma on the chemical and physical properties of vanillin-derived Schiff-base thermosets and the dip-coating process was investigated and compared to the influence of traditional post-treatment with UV-light. As a comparison, thermosets without post-treatment were also subjected to the coating procedure. The results document that UV post-treatment can induce the completion of the curing of the printed thermosets if complete curing is not reached during printing. Conversely, the plasma post-treatment does not contribute to the curing of the thermoset but causes some opening of the imine bonds and the regeneration of aldehyde functions. As a consequence, no great differences are observed between the not post-treated and plasma post-treated samples in terms of mechanical, thermal, and solvent-resistant properties. In contrast to the UV post-treatment, the plasma post-treatment of the thermosets induces a noticeable increase of the thermoset hydrophilicity ascribed to the reformation of amines on the thermoset surface. The successful coating process and the greatest uniformity of the lignosulfonate coating on the surface of plasma post-treated samples are considered to be due to the presence of these amines and aldehydes. The investigation of the UV shielding properties and antioxidant activities documents the increase of both properties with the increasing amount and uniformity of the formed coating. Interestingly, evident antioxidant properties are also shown by the noncoated thermosets, which are deduced to their chemical structures.


Clinical outcome evaluation following cyclosporine a treatment in moderate to severe psoriasis: a retrospective study.
This retrospective study was conducted on 193 patients treated in three Italian Psoriasis Units with the aim of evaluating the evolution of psoriasis severity and the safety of cyclosporin A (Sandimmun Neoral) in moderate to severe psoriasis, at the regimens usually employed in common clinical practice. Cyclosporin A (CyA) was administered for a mean period of 14 months, the mean number of treatment courses was 1.6 (range 1-4), and the mean dosage ranged from 1.5 to 3.1 mg/kg/die. Ninety percent of patients obtained complete therapeutic success or clinical remission, defined as complete clearance of lesions or clearance of lesions with residual minor pigmentations respectively, when treated with CyA in monotherapy. The mean Psoriasis Area and Severity Index (PASI) decreased from 23.31 before CyA administration to 5.64 at the end of treatment. The clinicians judgement on CyA tolerability was good/very good in 90 percent of cases. Adverse events occurred in 36 percent of patients, with hypertension being the most commonly reported (17.6 percent). The results of this study indicate that in the common clinical practice CyA in moderate to severe psoriasis is usually employed at low doses, resulting both safe and effective.


Ultrafast Chemistry of Water Radical Cation, H₂O•+, in Aqueous Solutions.
Oxidation reactions by radicals constitute a very important class of chemical reactions in solution. Radiation Chemistry methods allow producing, in a controlled way, very reactive oxidizing radicals, such as OH•, CO₃•-, NO₃•, SO₄•-, and N₃•. Although the radical cation of water, H₂O•+, with a very short lifetime (shorter than 1 ps) is the precursor of these radicals in aqueous solutions, its chemistry is usually known to be limited to the reaction of proton transfer by forming OH• radical. Herein, we stress situations where H₂O•+ undergoes electron transfer reaction in competition with proton transfer.


[Integration of the Internet into medical education].
The Internet promises dramatic changes in the way we learn and teach, the way we interact as a society. Networked technologies introduce interactivity and multimedia into the educational process. The student of the 21st century will use his/her PC as a learning station, as a tutoring system, as an information provider and as a communication center. Therefore the passive classroom (teacher-centered teaching) will evolve into active studio learning (student-centered learning). This will be achieved by new teaching techniques and standards of quality. The role of the new generation of educators is to create exploratory learning environments that offer a wide range of views on many subject areas and encourage active lifelong learning. This will be achieved by 1) placing courseware on the web where it can be accessed by remote students and by 2) finding and reviewing teaching materials obtained from www for possible integration into the local lecture material. The paper suggests strategies for introducing medical educators to networked teaching.


'My primary purpose is to protect the unborn child': Understanding pregnant women's perceptions of maternal vaccination and vaccine trials in Europe.
Despite the important benefits of maternal vaccination for pregnant women and newborns, vaccination uptake is low in many European countries. Differences in vaccination policies and recommendations, as well as concerns about vaccine safety can partly explain inadequate coverage rates and women's hesitancy to get vaccinated during pregnancy. This study aims to explore pregnant women's experiences, decision-making processes and perceptions towards maternal vaccination and maternal vaccine trials in France, Germany, Italy, Spain and the United Kingdom. Qualitative interviews and focus groups were conducted with 258 pregnant women identified through local research panels and snowballing. Topic guides translated in local languages were designed to explore women's awareness and perceptions of maternal vaccination, and willingness to participate in vaccine trials during pregnancy. A thematic analysis was conducted. Pregnant women were found to have low awareness about maternal vaccination, with many reporting not having received a recommendation to vaccinate from their doctors. Strong trust in health professionals indicate that strengthened recommendations could improve vaccination uptake. Vaccination decision-making in pregnancy was described in the context of a highly emotional period, generating anxiety and fears around the safety of vaccines. Pregnancy was also discussed as a period during which women develop nurturing and protective identities. However, depending on the information they received as well as influences from experts, families and peers, women either perceived vaccination as a threat to their babies' safety or as a means to protect them. Attitudes towards maternal vaccine trials were less ambiguous, with most pregnant women strongly rejecting the notion of taking part in trials. While strategies to improve pregnant women's awareness and perceptions of maternal vaccination are needed, it is equally important to understand why healthcare professionals may not be recommending vaccination. More coordinated strategies across Europe could help strengthen communication and trust in maternal vaccination.


Intermittent Hemiplegia in a Boy with Primary Moyamoya Disease: A Case Report from Iran.
Moyamoya is a rare chronic progressive occlusive cerebrovascular disease. Its manifestation varies from stroke, progressive learning impairment and transient ischemic attack to headache and seizure. There is no accepted medical treatment and surgery usually, is needed. We report here a case of 8 yr old boy referred to psychiatrist outpatient. An eight yr old boy with intermittent hemiplegia was brought to Imam Ali Clinic, Yazd, Iran in 2015 because his headache and medical problem began from 6 yr old. Stress and excitement exacerbated his condition. His first attack was at the age of 6 yr old. During attack, he had incontinence, severe headache, alogia, pallor, claudication and left hemiplegia (Left lower limb). Magnetic resonance angiography (MRA) was done and our diagnosis was moyamoya disease. Moyamoya is a mysterious disease and psychiatrists should consider it in differential diagnosis of alogia and plegia. Acute management of this disease is mainly symptomatic. Nowadays, surgery is a good choice and early diagnosis of this disease can change our patient's life.


Computer tools to support collaborative organization design: definition and analysis of the work at the Vanderbilt University Hospital and Clinic.
In November, 1993 The Vanderbilt University Hospital and Clinic (VUH/TVC) convened a 10-member Collaborative Organization Design (COD) team that represented a diagonal slice through the organization. This team, lead by Gelinas & James, an outside consulting firm, was charged to develop, recommend, and implement a new organizational design which would promote a stronger patient focus, increased efficiency, and lower costs. The COD process is structured to inspire and enable employees to rebuild their organization so that it can respond to the challenges and opportunities that exist within their environment, to customer needs, and their own aspirations. This manuscript describes several of the computer tools which were utilized in the definition and analysis of the work of patient care at VUH/TVC. Specific examples of the findings from this phase of the work are utilized to illustrate their use and value.


The influence of external subsidies on diet, growth and Hg concentrations of freshwater sport fish: implications for management and fish consumption advisories.
Mercury (Hg) contamination in sport fish is a global problem. In freshwater systems, food web structure, sport fish sex, size, diet and growth rates influence Hg bioaccumulation. Fish stocking is a common management practice worldwide that can introduce external energy and contaminants into freshwater systems. Thus, stocking can alter many of the factors that influence Hg concentrations in sport fish. Here we evaluated the influence of external subsidies, in the form of hatchery-raised rainbow trout Oncorhynchus mykiss on walleye Sander vitreus diet, growth and Hg concentrations in two freshwater systems. Stocking differentially influenced male and female walleye diets and growth, producing a counterintuitive size-contamination relationship. Modeling indicated that walleye growth rate and diet were important explanatory variables when predicting Hg concentrations. Thus, hatchery contributions to freshwater systems in the form of energy and contaminants can influence diet, growth and Hg concentrations in sport fish. Given the extensive scale of fish stocking, and the known health risks associated with Hg contamination, this represents a significant issue for managers monitoring and manipulating freshwater food web structures, and policy makers attempting to develop fish consumption advisories to protect human health in stocked systems.


The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates.
In sub-Saharan Africa, rates of sustained HIV virologic suppression remain below international goals. HIV resistance testing, while common in resource-rich settings, has not gained traction due to concerns about cost and sustainability. We designed a randomized clinical trial to determine the feasibility, effectiveness, and cost-effectiveness of routine HIV resistance testing in sub-Saharan Africa. We describe challenges common to intervention studies in resource-limited settings, and strategies used to address them, including: (1) optimizing generalizability and cost-effectiveness estimates to promote transition from study results to policy; (2) minimizing bias due to patient attrition; and (3) addressing ethical issues related to enrollment of pregnant women. The study randomizes people in Uganda and South Africa with virologic failure on first-line therapy to standard of care virologic monitoring or immediate resistance testing. To strengthen external validity, study procedures are conducted within publicly supported laboratory and clinical facilities using local staff. To optimize cost estimates, we collect primary data on quality of life and medical resource utilization. To minimize losses from observation, we collect locally relevant contact information, including Whatsapp account details, for field-based tracking of missing participants. Finally, pregnant women are followed with an adapted protocol which includes an increased visit frequency to minimize risk to them and their fetuses. REVAMP is a pragammatic randomized clinical trial designed to test the effectiveness and cost-effectiveness of HIV resistance testing versus standard of care in sub-Saharan Africa. We anticipate the results will directly inform HIV policy in sub-Saharan Africa to optimize care for HIV-infected patients.


Home bias and local equity portfolio decisions of Chinese insurance institutional investors.
Our paper explores whether Chinese insurance companies exhibit a local preference in deciding their equity portfolios and the incentive of this preference. Our research finds that Chinese insurance institutional investors significantly tilt to invest in local firms geographically close to them, and local investments do not significantly outperform non-local investments. The results indicate that the behavioral aspect of home bias, rather than information advantage, play a more significant role in deciding equity holdings of China's insurance companies. Additionally, local equity preference is more pronounced in dialect-segmented areas and life insurance firms. This paper incorporates hometown identification into the analysis framework of insurance companies' portfolio decision-making and enriches the research of their investing strategies from the perspective of behavioral finance.


Ab initio description of p-shell hypernuclei.
We present the first ab initio calculations for p-shell single-Λ hypernuclei. For the solution of the many-baryon problem, we develop two variants of the no-core shell model with explicit Λ and Σ(+),Σ(0),Σ(-) hyperons including Λ-Σ conversion, optionally supplemented by a similarity renormalization group transformation to accelerate model-space convergence. In addition to state-of-the-art chiral two- and three-nucleon interactions, we use leading-order chiral hyperon-nucleon interactions and a recent meson-exchange hyperon-nucleon interaction. We validate the approach for s-shell hypernuclei and apply it to p-shell hypernuclei, in particular to (Λ)(7)Li, (Λ)(9)Be, and (Λ)(13)C. We show that the chiral hyperon-nucleon interactions provide ground-state and excitation energies that generally agree with experiment within the cutoff dependence. At the same time we demonstrate that hypernuclear spectroscopy provides tight constraints on the hyperon-nucleon interactions.


DEMONSTRATION OF LYSOGENY IN STABLE L FORMS OF PROTEUS MIRABILIS.
Taubeneck, Udo (Institut für Mikrobiologie und Experimentelle Therapie, Jena, Germany). Demonstration of lysogeny in stable L forms of Proteus mirabilis. J. Bacteriol. 86:1265-1269. 1963.-Stable L forms of eight different lysogenic Proteus mirabilis strains have proved to be lysogenic. In an additional strain, phage production was induced upon transfer into the stable L form. This demonstrates that the stable L forms, like their parent bacillary types, are capable of forming mature phage. Their phage resistance is not due to an inability to form mature phage but to a loss of phage receptors. In some instances, the transition into the stable L form is associated with altered phage production, usually with increased phage production, in comparison with the parental bacillary type.


Evidence-based paediatrics.
Evidence-based medicine is practised widely in some specialties and is now part of many undergraduate and graduate medical curricula. However, the extent to which it is used in clinical paediatric practice is not known and its expansion remains a major challenge. Access to technology which facilitates literature searching, and development of journals addressing specific paediatric problems, will encourage the use of evidence-based medicine by the busy paediatrician. Informed practice of evidence-based medicine will ensure that clinical expertise is complemented by a thorough search, evaluation and judicious application of relevant information from the medical literature.


Blood cholesterol in late-life and cognitive decline: a longitudinal study of the Chinese elderly.
Previous studies regarding the lipid-cognition relation in older adults are limited and have generated mixed results. We thus examined whether higher blood cholesterol concentrations were associated with faster cognitive decline in a community-based longitudinal study of Chinese elderly. The study included 1,159 Chinese adults aged over 60 years (women: 48.7%, mean age: 79.4 years), who were free of dementia, Parkinson disease and stroke at the baseline. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), were assessed at the baseline. Global cognitive functions were assessed using the Chinese Mini-Mental State Examination (MMSE) at in 2009, 2012 and 2014. Association between blood cholesterol and repeated cognitive function was analyzed with linear mixed models, adjusting for sociodemographic information, behavior and lifestyle, depression symptoms, physical examination, hypertension, and laboratory indexes. Higher baseline TC and LDL-C concentrations were significantly associated with greater cognitive decline. Adjusted mean difference in cognitive decline rate, comparing two extreme quartiles, was 0.28 points (MMSE score) per year (95% confident interval (CI): -0.54,-0.02; P-trend = 0.005) for TC and 0.42 points per year (95% CI: -0.69, -0.16; P-trend = 0.006) for LDL-C. In a subgroup analysis, the associations between all lipids and cognitive decline appeared to be more pronounced among individuals aged 100 years or older (n = 90), relative to others. Higher blood concentrations of TC and LDL-C in late-life were associated with faster global cognitive decline.


Arterial versus venous bypass grafts in patients with in-stent restenosis.
In patients who develop in-stent restenosis, successful revascularization can be difficult to achieve using percutaneous methods. This study was designed to verify the surgical results in this setting and to evaluate the potential beneficial role of arterial bypass conduits. Sixty consecutive coronary artery bypass patients with previous in-stent restenosis and 60 control cases were randomly assigned to receive an arterial conduit (either right internal thoracic or radial artery; study group) or a great saphenous vein graft (control group) on the first obtuse marginal artery to complete the surgical revascularization procedure. At a mean follow-up of 52+/-11 months, patients were reassessed clinically and by angiography. Freedom from clinical and instrumental evidence of ischemia recurrence was found in 19 of 60 subjects in the study group versus 45 of 60 in the control series (P=0.01). The results of the arterial grafts were excellent in both the study and control groups (right internal thoracic artery patency rate, 19 of 20 for both, and radial artery patency rate, 20 of 20 versus 19 of 20; P=0.99). Saphenous vein grafts showed lower patency rate than arterial grafts in both series and had extremely high failure rate in the study group (patency rate, 10 of 20 in the study group versus 18 of 20 in the control group; P=0.001). Use of venous graft was an independent predictor of failure in the study group, whereas hypercholesterolemia was associated with graft failure in both series. Venous grafts have an high incidence of failure among cases who previously developed in-stent restenosis, whereas the use of arterial conduits can improve the angiographic and clinical results. Arterial grafts should probably be the first surgical choice in this patient population.


Note: A small roll angle measurement method with enhanced resolution based on a heterodyne interferometer.
Small roll angle is hard to be measured directly by commercial interferometer instruments due to their low sensitivities in axial direction. A method for its measurement based on a heterodyne interferometer is presented, which adopts accessories including a half wave plate, a multiple-reflector, and a phase meter to achieve test by detecting phase differences between the measurement and reference arms. Mathematical model reveals the resolution will be improved by increasing pass times through the half wave plate. The theoretical resolution is up to 0.19 in. when the pass times increase to three and the phase meter resolution is 0.01°. The proposed method is proved by the experiment.


Analysis of Risk Factors for Multiantibiotic-Resistant Infections Among Surgical Patients at a Children's Hospital.
To identify the potential risk factors for multiantibiotic-resistant infections and provide sufficient evidence for multiantibiotic resistance prevention and control. We conducted a retrospective study of all patients in pediatric orthopedics, pediatric heart surgery, and pediatric general surgery at a level 3, grade A children's hospital from January to December 2016. The clinical laboratory information monitoring system and the medical record system were used to collect patient information regarding age, surgery type, preoperative length of stay, admission season, incision type, preoperative infection, intraoperative blood loss, postoperative use of invasive equipment, duration of catheter drainage, and timepoint of intraoperative prophylactic antibiotics administration. We used logistic univariate and multivariate regression analysis to analyze the potential risk factors for multiantibiotic-resistant infections among pediatric surgical patients. SPSS 21.0 and Excel software packages were used for the statistical analysis. In total, 2,973 patients met the inclusion criteria: 1,247 patients in pediatric orthopedics, 1,089 patients in pediatric heart surgery, and 637 patients in pediatric general surgery. At the end of the study, 113 patients were multiantibiotic-resistant infection cases; the rate of multiantibiotic-resistant infections was 3.80%, and the detection rate was 84.79%. Multivariate analysis indicated that the multiantibiotic-resistant infection cases were influenced by age, department, admission season, incision type, preoperative infection, and duration of catheter drainage. Age, department, admission season, incision type, preoperative infection, and duration of catheter drainage may provide possible evidence for prevention and control strategies of multiantibiotic-resistant infections.


Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson's disease.
We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1 (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers. Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097) and anterior and posterior putamen (p < 0.0001) of PD patients compared to controls. Using the posterior putamen as the main region of interest resulted in the greatest accuracy (sensitivity 0.79, specificity 0.92). These findings show that TRODAT imaging can accurately differentiate early PD patients from controls and has the potential to improve the diagnosis of patients with early signs of PD.


Lightweight predicate extraction for patient-level cancer information and ontology development.
Knowledge engineering for ontological knowledgebases is resource and time intensive. To alleviate these issues, especially for novices, automated tools from the natural language domain can assist in the development process of ontologies. We focus towards the development of ontologies for the public health domain and use patient-centric sources from MedlinePlus related to HPV-causing cancers. This paper demonstrates the use of a lightweight open information extraction (OIE) tool to derive accurate knowledge triples that can lead to the seeding of an ontological knowledgebase. We developed a custom application, which interfaced with an information extraction software library, to help facilitate the tasks towards producing knowledge triples from textual sources. The results of our efforts generated accurate extractions ranging from 80-89% precision. These triples can later be transformed to OWL/RDF representation for our planned ontological knowledgebase. OIE delivers an effective and accessible method towards the development ontologies.


Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and nonencephalitogenic CD4+ T cell lines in vitro.
Experimentally induced and naturally occurring inflammatory diseases of the central nervous system (CNS) are often associated with a breakdown of the blood-brain barrier and edema within the CNS itself. CD4+ T cells are now clearly implicated in the pathogenesis of the induced CNS disease, experimental autoimmune encephalomyelitis, and previous in vivo experiments had indicated that these cells may be capable of directly damaging the CNS vasculature. To assess the capacity of CD4+ T cells to damage brain vascular endothelial cells (EC) in vitro, two lines with specificity for myelin basic protein and OVA were prepared and added to cultures of EC. We show here that both lines, when added in a resting state, severely disrupt the EC monolayers in an Ag-specific manner. The interaction is dependent on the recognition of Ag in the context of MHC class II and is blocked in the presence of mAb specific for CD4. Addition of T cell lines preactivated on irradiated thymocyte APC caused a high level of Ag nonspecific damage to the EC, which was not blocked by the addition of anti-CD4 mAb. Supernatants derived from these latter cells did not alone damage the EC monolayers despite the presence of TNF activity suggesting that T cell-EC contact may be required for these cell lines to mediate their effector function. Both resting and preactivated lines adhered strongly to the EC in the absence of Ag. The capacity of CD4+ T cells to strongly adhere to, and disrupt the integrity of, brain vascular EC may be important in the early stages of CNS disease mediated by this cell type.


Molecular Targeting of ERKs/RSK2 Signaling Axis in Cancer Prevention.
RSK2 is a downstream signaling protein of ERK1 and ERK2 and plays a key role in physiological homeostasis. For this reason, RSK2 is a highly conserved protein among the p90RSK family members. In its location in the signaling pathway, RSK2 is a kinase just upstream of transcription and epigenetic factors, and a few kinases involved in cell cycle regulation and protein synthesis. Moreover, activation of RSK2 by growth factors is directly involved in cell proliferation, anchorage-independent cell transformation and cancer development. Direct evidences regarding the etiological roles of RSK2 in cancer development in humans have been published by our research group illustrating that elevated total- and phospho-RSK2 protein levels mediated by ERK1 and ERK2 are higher in skin cancer tissues compared to normal skin tissues. Notably, it has been shown that RSK2 ectopic expression in JB6 Cl41 cells induces cell proliferation and anchorage- independent cell transformation. Importantly, knockdown of RSK2 suppresses Ras-mediated foci formation and anchorage-independent colony growth of cancer cells. Kaempferol is a one of the natural compounds showing selectivity in inhibiting RSK2 activity in epidermal growth factor-induced G1/S cell cycle transition and cell transformation. Thus, ERKs/RSK2 signaling axis is an important target signaling molecule in chemoprevention.


Substance use disorders among African-American men in the rural south: A scoping review.
African American (AA) men in the rural South may be at high risk for experiencing adverse health outcomes from substance use (SU). We conducted a scoping review to explore the research on SU among rural AA men in the rural South of the United States (US). Ten articles addressed the following thematic areas pertaining to SU: factors associated with SU (n = 6), associations between substance use and health outcomes (n = 2), and the influence of impulsivity on SU (n = 2). Additional research on SU among AA men in the rural South is needed, particularly pertaining to treatment-related considerations.


Proton tracking for medical imaging and dosimetry.
For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy, where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction - including two in the U.K.. The characteristics of a new silicon micro-strip detector based system for this application will be presented. The array uses specifically designed large area sensors in several stations in an x-u-v co-ordinate configuration suitable for very fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of giving information on the path of high energy protons entering and exiting a patient. This will allow proton computed tomography (pCT) to aid the accurate delivery of treatment dose with tuned beam profile and energy. The tracker will also be capable of proton counting and position measurement at the higher fluences and full range of energies used during treatment allowing monitoring of the beam profile and total dose. Results and initial characterisation of sensors will be presented along with details of the proposed readout electronics. Radiation tests and studies with different electronics at the Clatterbridge Cancer Centre and the higher energy proton therapy facility of iThemba LABS in South Africa will also be shown.


Low ankle-brachial index predicts an adverse 1-year outcome after acute coronary and cerebrovascular events.
Low ankle-brachial Index (ABI) identifies patients with symptomatic and asymptomatic peripheral arterial disease. The aim of this study was to correlate ABI value (normal or low) with 1-year clinical outcome in patients hospitalized for acute coronary syndromes or cerebrovascular diseases (CVD). ABI was measured in consecutive patients hospitalized because of acute myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA). An ABI lower than or equal to 0.90 was considered abnormal. The primary outcome of the study was the composite of non-fatal acute myocardial infarction, non-fatal ischemic stroke, and death from any cause during the year following the index event. An abnormal ABI was found in 27.2% of 1003 patients with acute coronary syndromes, and in 33.5% of 755 patients with acute CVD. After a median follow-up of 372 days, the frequency of the primary outcome was 10.8% (57/526) in patients with abnormal ABI and 5.9% (73/1232) in patients with normal ABI [odds ratio (OR) 1.96; 95% CI 1.36-2.81]. Death was more common in patients with abnormal ABI (OR 2.05; 95% CI 1.31-3.22). Cardiovascular mortality accounted for 81.7% of overall mortality. ABI was predictive of adverse outcome after adjustment for vascular risk factors in the logistic regression analysis (OR 1.93; 95% CI 1.24-3.01). The predictive value of ABI was mainly accounted for by patients hospitalized for acute coronary syndromes (adverse outcome: 12.8% in patients with abnormal ABI and 5.9% in patients with normal ABI, OR 2.35; 95% CI 1.47-3.76). An abnormal ABI can be found in one-third of patients hospitalized for acute coronary or cerebrovascular events and is a predictor of an adverse 1-year outcome.


[Change in the level of sphingosine in rat liver nuclei and cells during oncogene superexpression induced by cycloheximide].
Changes in the sphingosine content in rat liver cells and nuclei have been studied with reference to the level of nuclear oncogene expression, induced by cycloheximide (0.1, 0.5 and 3.0 mg/kg). It has been found that only the sublethal (3 mg/kg) dose of cycloheximide which induces the superexpression of c-fos and c-myc oncogenes can promote sphingosine accumulation in the cell. At the moment of enhanced expression of nuclear oncogenes, the maximum content of free sphingosine exceeds the control level 1.5- and 3-fold in the cell and in the nuclei, respectively. The difference in the sphingosine accumulation patterns in the cell and in the nuclei testifies to the fact that sphingomyelin metabolism is more active in the nuclei than in the cell. Sphingosine accumulation in the nuclei is characterized by coordination of sphingomyelinase activity and changes in the sphingomyelin content. A comparative analysis of activities of enzymes of sphingomyelin (sphingomyelinase) and phosphatidyl inositol (phosphatidyl inositol kinase) cycles indicates that in the nuclei the activation of the sphingomyelin cycle forestalls the cycloheximide-induced activation of the phosphatidyl inositol cycle and the maximal accumulation of nuclear oncogene mRNAs. A model of activation of oncogene expression with participation of sphingosine inhibiting protein kinase C and activating casein kinase II, the key enzymes of the signal transduction system of cell proliferation and differentiation, is proposed.


Role modelling and students' professional development.
Patients expect to be cared for by nurses who are not only competent but also behave professionally, so students must be educated to develop professional qualities. The Nursing and Midwifery Council stipulates that professional values must underpin education as well as practice (NMC, 2010a). Much has been written on the qualities of an effective role model and the potential barriers to becoming one. This article focuses on preregistration adult nursing education and role modelling, with a slant towards the development of professionalism, as opposed to skills competence. Attention is paid to the identity of students' role models and strategies for role modelling linked to teaching and the curriculum. Practice and academic staff have an equal stake in nurse education; for them to be seen equally as role models, there has to be a partnership approach to that education. Both practice and academic staff are able to exemplify behaviours and attitudes that directly influence the development of professionalism. This article is intended to stimulate discussion within and between nurse educators and practice-based staff about the impact their role modelling has on the development of adult nursing students' professional practice.


Interleukin 2- and interferon alpha induced natural killer cell activity as a marker of progression in hairy cell leukemia.
Hairy cell leukemia (HCL), a rare B-cell chronic lymphoproliferative disorder, is often accompanied by immune abnormalities. A marked impairment of the natural killer cell-mediated cytotoxicity (NK activity) has been reported in most patients at diagnosis. In the present report a long-term follow-up study of NK activity of splenectomized HCL patients is recorded. Among patients who persisted with stable disease two groups, one with normal NK activity, and another with low NK activity, could be recognized. Patients with progressive stage were characterized by a low NK cytotoxic activity. In vitro tests showed that interferon alpha (IFN-alpha) and interleukin 2 (IL2) could increase the NK activity to normal levels only in HCL patients with stable disease, while in progressive HCL these cytokines showed a significantly decreased effect. These results indicate that cytokine-induced NK cytotoxicity appears to be a valuable parameter in assessing the stage of HCL.


[Chronic gout: causes, clinical manifestations, treatment].
Why chronic gout, that is mostly a well diagnosed and controlled disease if it is timely and systematically treated with allopurinol, becomes a topical public health problem following 50 years after the introduction of pathogenetic therapy with xantine oxidase inhibitors is under consideration. The principles of rational therapy for chronic gouty arthritis are outlined.


Psychosocial Adjustment and Mental Distress Associated With In-Game Purchases Among Japanese Junior High School Students.
In-game purchases, including microtransactions and loot box spending, are the monetization systems of free-to-play online games. Although some studies have suggested that excessive in-game purchases increase the risk of psychosocial maladjustment and mental distress as well as predict future problematic gaming and gambling practices, empirical studies on problematic behavioral patterns related to in-game purchasing among adolescents are lacking. This study sought to explore whether knowing the style of in-game purchases (non-purchase, planned purchase, or unplanned purchase) could be useful when characterizing maladaptive behavior among adolescents from the perspective of psychosocial adjustment and mental distress. A total of 335 junior high school students (aged 12-15 years) participated in the survey and completed a questionnaire assessing daily online gaming usage, in-game purchases, psychosocial adjustment, and mental distress. The results showed that (1) 30.7% of students had previously made in-game purchases, and at least 14.0% had made unplanned in-game purchases; (2) 19.2% of the users who had made unplanned purchases had spent greater than or equal to their actual monthly allowance within the past month, and (3) unplanned purchase gamers exhibited more behavioral problems and peer problems regarding psychosocial adjustment compared to planned purchase gamers, and more overall difficulties compared to non-purchasers. Meanwhile, more hyperactivity/inattention was seen among in-game purchasers compared to non-purchasers, regardless of whether the purchase was planned or unplanned. These findings support that understanding whether adolescents make unplanned in-game purchases could be a useful approach to describing the characteristics of online gamers with maladaptive tendencies.


Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique.
Rice is one of the most widely consumed foods all over the world. Various diseases and deficiency disorders impact the rice crop's growth, thereby hampering the rice yield. Therefore, proper crop monitoring is very important for the early diagnosis of diseases or deficiency disorders. Diagnosis of diseases and disorders requires specialized manpower, which is not scalable and accessible to all farmers. To address this issue, machine learning and deep learning (DL)-driven automated systems are designed, which may help the farmers in diagnosing disease/deficiency disorders in crops so that proper care can be taken on time. Various studies have used transfer learning (TL) models in the recent past. In recent studies, further improvement in rice disease and deficiency disorder diagnosis system performance is achieved by performing the ensemble of various TL models. However, in all these DL-based studies, the segmentation of the region of interest is not done beforehand and the infected-region extraction is left for the DL model to handle automatically. Therefore, this article proposes a novel framework for the diagnosis of rice-infected leaves based on DL-based segmentation with bitwise logical AND operation and DL-based classification. The rice diseases covered in this study are bacterial leaf blight, brown spot, and leaf smut. The rice nutrient deficiencies like nitrogen (N), phosphorous (P), and potassium (K) were also included. The results of the experiment conducted on these datasets showed that the performance of DeepBatch was significantly improved as compared to the conventional technique.


Effect of Combined Perftoran and Indocyanine Green-Photodynamic Therapy on HypoxamiRs and OncomiRs in Lung Cancer Cells.
Indocyanine green (ICG) is a nontoxic registered photosensitizer used as a diagnostic tool and for photodynamic therapy (PDT). Hypoxia is one the main factors affecting PDT efficacy. Perfluorodecalin emulsion (Perftoran®) is a known oxygen carrier. This study investigated the effect of Perftoran® on ICG/PDT efficacy in presence and absence of Perftoran® via evaluation of phototoxicity by MTT; hypoxia estimation by pimonidazole, HIF-1α/β by ELISA, and 17 miRNAs (tumor suppressors, oncomiRs, and hypoxamiRs) were analyzed by qPCR. Compared to ICG/PDT, Perftoran®/ICG/PDT led to higher photocytotoxicity, inhibited pimonidazole hypoxia adducts, inhibited HIF-1α/β concentrations, induced the expression of tumor-suppressing miRNAs let-7b/d/f/g, and strongly inhibited the pro-hypoxia miRNA let-7i. Additionally, Perftoran®/ICG/PDT suppressed the expression of the oncomiRs miR-155, miR-30c, and miR-181a and the hypoxamiRs miR-210 and miR-21 compared to ICG/PDT. In conclusion, Perftoran® induced the phototoxicity of ICG/PDT and inhibited ICG/PDT-hypoxia via suppressing HIF-α/β, miR-210, miR-21, let-7i, miR-15a, miR-30c, and miR-181a and by inducing the expression of let-7d/f and miR-15b.


Pharmacokinetic drug evaluation of ceftobiprole for the treatment of MRSA.
Methicillin-resistant Staphylococcus aureus (MRSA), while decreasing in overall incidence, is still a prominent concern world-wide. New agents coming to market in the last 10 years allow practitioners to optimize treatment for MRSA infections. Ceftobiprole is a cephalosporin agent with MRSA activity, currently approved in selected countries for the treatment of community-acquired pneumonia and hospital-acquired pneumonia. Areas covered: Relevant literature regarding spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical trials will be discussed. Expert opinion: Ceftobiprole is an addition to a growing number of antimicrobials with activity against MRSA. Concern for appropriate dosing in critically ill patients remains due to its ineffectiveness for the treatment of ventilator-associated pneumonia (VAP). While ceftobiprole has activity against gram-negative organisms, the allowance for use of an additional agent for gram-negative infections in clinical trials limits recommendations for monotherapy for empirical treatment of HAP. Ceftobiprole's place in therapy will lie in its activity against gram positive organisms, such as Streptococcus spp. and Staphylococcus spp.


Reduced growth hormone response to L-dopa and pyridostigmine in obesity.
The purpose of this study was to evaluate growth hormone (GH) secretion and clarify the factors influencing GH secretion in obesity. Nine obese subjects and eight controls were recruited. We compared the GH response to L-dopa with or without pyridostigmine pretreatment in obese and control subjects. Plasma glucose, insulin, insulin-like growth factor I (IGF-I) and free fatty acid (FFA) were also measured. Growth hormone responses and GH area under the response curve (AUC) to L-dopa were significantly lower in obese subjects than those in controls. Pyridostigmine significantly enhanced the GH response to L-dopa in both obese and control subjects. However, enhanced GH responses in obese subjects were attenuated biologically and lower than those in controls with L-dopa only. Plasma levels of insulin insulin and FFA were significantly higher in obese subjects than those in controls. Body mass index had a positive correlation with the levels of insulin and FFA. However, GH AUC had an inverse correlation with insulin and FFA in obese subjects and controls. Stepwise multiple regression analysis showed a highly significant effect of FFA on GH AUC, but no independent influence of other factors on GH AUC. The reduced GH secretion found in this study suggests an increase in somatostatinergic tone and a diminished release of GHRH from the hypothalamus in obesity. However, other factors including hyperinsulinemia and increased plasma FFA may play an important additional role in the secretory dysfunction of GH in obesity.


Chirality generated by flows in pseudocyanine dye J-aggregates: revisiting 40 years old reports.
Spontaneous symmetry breaking in J-aggregates of cyanine dyes has a long history in chemical literature. In 1976, Honda and Hada claimed that they had achieved chiral induction (CD) by stirring J-aggregates of pseudocyanine. However, this report is controversial, as the combinations of linear dichroism and birefringence can lead to artifactual circular dichroic signals that are unrelated to molecular chirality. A Mueller matrix spectroscopy study, with an approach for the application of a gradient of the shear rate (solution layer between a rotating and a fixed disk) that differs from the simple vortex stirring used in the original report, shows that true CD can be induced in the sample. The phenomenon is discussed, taking into account the flow dynamics that allows the alignment of the aggregate particles and the gradient of shear rates that determines their folding/torsion, which leads to a chiral excitonic transition.


Phenylpropanoid 2,3-dioxygenase involved in the cleavage of the ferulic acid side chain to form vanillin and glyoxylic acid in Vanilla planifolia.
Enzyme catalyzing the cleavage of the phenylpropanoid side chain was partially purified by ion exchange and gel filtration column chromatography after (NH4)2SO4 precipitation. Enzyme activities were dependent on the concentration of dithiothreitol (DTT) or glutathione (GSH) and activated by addition of 0.5 mM Fe2+. Enzyme activity for ferulic acid was as high as for 4-coumaric acid in the presence of GSH, suggesting that GSH acts as an endogenous reductant in vanillin biosynthesis. Analyses of the enzymatic reaction products with quantitative NMR (qNMR) indicated that an amount of glyoxylic acid (GA) proportional to vanillin was released from ferulic acid by the enzymatic reaction. These results suggest that phenylpropanoid 2,3-dioxygenase is involved in the cleavage of the ferulic acid side chain to form vanillin and GA in Vanilla planifolia.


Polygalacturonase gene pgxB in Aspergillus niger is a virulence factor in apple fruit.
Aspergillus niger, a saprophytic fungus, is widely distributed in soil, air and cereals, and can cause postharvest diseases in fruit. Polygalacturonase (PG) is one of the main enzymes in fungal pathogens to degrade plant cell wall. To evaluate whether the deletion of an exo-polygalacturonase gene pgxB would influence fungal pathogenicity to fruit, pgxB gene was deleted in Aspergillus niger MA 70.15 (wild type) via homologous recombination. The ΔpgxB mutant showed similar growth behavior compared with the wild type. Pectin medium induced significant higher expression of all pectinase genes in both wild type and ΔpgxB in comparison to potato dextrose agar medium. However, the ΔpgxB mutant was less virulent on apple fruits as the necrosis diameter caused by ΔpgxB mutant was significantly smaller than that of wild type. Results of quantitive-PCR showed that, in the process of infection in apple fruit, gene expressions of polygalacturonase genes pgaI, pgaII, pgaA, pgaC, pgaD and pgaE were enhanced in ΔpgxB mutant in comparison to wild type. These results prove that, despite the increased gene expression of other polygalacturonase genes in ΔpgxB mutant, the lack of pgxB gene significantly reduced the virulence of A. niger on apple fruit, suggesting that pgxB plays an important role in the infection process on the apple fruit.


Sperm parasitism in ants: selection for interspecific mating and hybridization.
Interspecific mating in eusocial Hymenoptera can be favored under certain conditions even if all hybrid offspring are completely infertile. This exploits two key features of the eusocial Hymenoptera: a haplodiploid genetic system and reproductive division of labor in females. Interspecifically mated queens can still produce viable sons that will mate intraspecifically. Apparent reduced fitness resulting from producing infertile daughter gynes can be also offset by advantages conferred by hybrid workers. An important advantage is likely to be superior ability at using marginal habitats. Interspecifically mated queens can nest in sites where intraspecific competition will be low. By mating interspecifically, a queen trades expected reproductive success through female offspring for a higher probability of achieving some reproductive success. Females that mate interspecifically can be considered "sperm parasites" on the males of the other species. I provide evidence that sperm parasitism is responsible for widespread hybridization in North America among two species of the ant subgenus Acanthomyops (genus Lasius), and review evidence for sperm parasitism in other hybridization phenomena in ants. Sperm parasitism in ants represents a novel form of social parasitism in ants and a dispersal polymorphism. It may also act as a precursor to the evolution of some other recently discovered phenomena, such as genetic caste determination.


The benefit of pancreatic cancer surveillance in carriers of germline BRCA1/2 pathogenic variants.
Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance. A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC. A total of 180 asymptomatic carriers participated in the screening programs, including 57 (31.7%) with BRCA1 PVs, 121 (67.2%) with BRCA2 PVs, and 12 (6.6%) with PVs in BRCA1/2 and other genes, for a median follow-up period of 4 years. Ninety-one individuals (50.5%) fulfilled the International Cancer of the Pancreas Screening (CAPS) criteria for surveillance whereas 116 (64.4%) fulfilled the American College of Gastroenterology (ACG) criteria. There were four cases of adenocarcinoma and four cases of grade 1-neuroendocrine tumor (G1-NET). All were BRCA2 carriers, and two had no family history of PDAC. Three cancer patients were at resectable stages (IA, IIA, IIB) whereas one had a stage IIIB tumor. Of the G1-NET cases, one had surgery and the others were only followed. Success rate for detection of confined pancreatic carcinoma was thus 1.6% (three of 180) in the whole cohort, 1.6% (two of 116) among individuals who fulfilled ACG criteria and 2.2% (two of 91) in those fulfilling CAPS criteria for surveillance. Despite the low detection rate of PDAC and its' high-risk neoplastic precursor lesions among BRCA1/2 carriers undergoing pancreatic surveillance, 75% of cancer cases were detected at a resectable stage.


Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational study.
B cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women. In all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation. Compared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women. In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women. The most notable exceptions to the above were the percentages of naïve B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non-pregnant women) and of CD24(hi)CD38(hi) regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women). According to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection.


Alcohol and European transformation.
Against the background of papers and discussions from the East-West seminar at the European Conference on Health, Society and Alcohol, the differences and similarities in eastern and western European transformation processes are discussed. After some remarks on the general nature of eastern transition and western integration, the two sides of Europe are compared with respect to various alcohol-specific issues. It will be shown that the ongoing transition touches alcohol-related phenomena on a broad spectrum, and no single characterization (e.g. commercialization and the rise of market interests) is sufficient alone. The changing balance between state, markets and civil society provides, however, an interesting perspective for comparing alcohol-related changes in various European societies. Finally, the prospects for a common European alcohol agenda are discussed briefly from the point of view of international mobilization on the dimensions of state, markets and civil society. There are signs of increased cooperation along all dimensions, but an all-European alcohol agenda seems unlikely.


N-Acetyl glycals are tight-binding and environmentally insensitive inhibitors of hexosaminidases.
Mono-, di- and trisaccharide derivatives of 1,2-unsaturated N-acetyl-d-glucal have been synthesized and shown to function as tight-binding inhibitors/slow substrates of representative hexosaminidases. Turnover is slow and not observed in the thioamide analogue, allowing determination of the 3-dimensional structure of the complex. Inhibition is insensitive to pH and to mutation of key catalytic residues, consistent with the uncharged character of the inhibitor. These properties could render this inhibitor class less prone to development of resistance.


Effects of 3-phosphoglycerate and other metabolites on the activation of AMP-activated protein kinase by LKB1-STRAD-MO25.
Skeletal muscle contraction results in the phosphorylation and activation of the AMP-activated protein kinase (AMPK) by an upstream kinase (AMPKK). The LKB1-STE-related adaptor (STRAD)-mouse protein 25 (MO25) complex is the major AMPKK in skeletal muscle; however, LKB1-STRAD-MO25 activity is not increased by muscle contraction. This relationship suggests that phosphorylation of AMPK by LKB1-STRAD-MO25 during skeletal muscle contraction may be regulated by allosteric mechanisms. In this study, we tested an array of metabolites including, glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, 3-phosphoglycerate (3-PG), glucose 1-phosphate, glucose 1,6-bisphosphate, ADP, carnitine, acetylcarnitine, IMP, inosine, and ammonia for allosteric regulation. ADP inhibited both AMPK and LKB1-STRAD-MO25 actions, but probably is not important physiologically because of the low free ADP inside the muscle fiber. We found that 3-PG stimulated LKB1-STRAD-MO25 activity and allowed for increased AMPK phosphorylation. 3-PG did not stimulate LKB1-STRAD-MO25 activity toward the peptide substrate LKB1tide. These results have identified 3-PG as an AMPK-specific regulator of AMPK phosphorylation and activation by LKB1-STRAD-MO25.


Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment.
To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment. In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, n = 5) with those of treatment-naïve women with such fractures (Fx+, n = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18-20 months after the last injection were studied (Dmab/Fx-, n = 5). We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4-8 weeks after the fracture. Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and CTSK (2.6-fold) mRNA. The respective values of Dmab/Fx- women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude. Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation.


The autonomic nervous system and its relationship to tubal ovum transport--a reappraisal.
The role of the autonomic nervous system in controlling ovum transport remains obscure. Although not studied extensively in the oviduct, the para-sympathetic nervous system does not appear to significantly influence ovum transport. The sympathetic nervous system of the oviduct and its pharmacology have been studied more thoroughly. Despite this, little information is available concerning cellular mechanisims of adrenergically altered motility or transport. In spite of much speculation, the weight of evidence suggests that, at least in the rabbit, the sympathetic nervous system plays a minor role in the control of ovum transport.


Early Laparoscopic Ileostomy Reversal After Rectal Cancer Surgery - Technique and Outcomes.
Background: A temporary diverting ileostomy (TDI) is performed in a significant number of patients undergoing colorectal surgery. The best timing for ileostomy reversal (IR), early or late after its formation and the proper technique used for its closure are controversial.The objective of the present study is to describe the particular aspects of the laparoscopic technique of ileostomy reversal and to analyze the outcomes of its early closure. Methods: A retrospective analysis on all the patients who underwent laparoscopic ileostomy reversal (LIR) after MIS rectal surgery between 2015 and 2018 in Ponderas Academic Hospital was performed. No patient was excluded from the study. The outcomes of the early laparoscopic closure of the diverting ileostomy (less than 30 days) were analyzed and compared with the standard closure ones. Results: Twenty-one patients, (10 males), average age and BMI of 57 years (range 33-77) and 21.6 kg/m2 (range 14.4-34) were included into the study. All the procedures were completed laparoscopically. No patient was lost from follow-up. The laparoscopic ileostomy reversal was performed at 50.4 days (range 7-150) from the open (1 patient) or laparoscopic (20 patients) rectal cancer resection. Twelve patients had preoperative RCT (48%), 17 low colorectal anastomosis and the coloanal one was performed in three patients with TDI. Eleven patients (52%) had an early ileostomy reversal after 23.6 days (7-30 days). A very early LIR (7-10 days) was necessary in 3 patients with complicated evolution after TDI. No significant intra-operative or postoperative complications between the two subgroups of early or late LIR was encountered. The hospital stay (LOS) after LIR was 3.9 days (2-5) with no difference between the two subgroups. We encountered one postoperative complication (5%), - enteral bleeding conservatively treated. Conclusions: Laparoscopic ileostomy reversal may be considered as a primary option for temporary diverting ileostomy after colorectal resection. The early ileostomy reversal is safe and improved postoperative outcomes in are demonstrated selected patients. Careful investigation and rigorous selection of the patients for EIR is mandatory.


Role of the Penrose drain in the management of VLBW infants with perforated necrotising enterocolitis.
We studied the effectiveness of the Penrose drain in very low birth weight infants with BW < 1500g with perforated necrotizing Enterocolitis. We reviewed the infants with perforated NEC over the 9 years between 1995-2004. The inclusive criteria was free intraperitoneal air in VLBW infants < 1500g. A total 22 infants were studied. Gestational age ranged from 23 to 33 weeks. Perforated NEC was diagnosed on PFA. In all infants a Penrose drain was inserted in either the right or left lower abdominal quadrants. Most of the infants fell in the BW range 800g to 980g with median age of 16 days. The incidence of Perforated NEC was very high in females (81.8%) as compared to males (18.2%). A Penrose drain was inserted on the same day when the pneumoperitoneum was diagnosed. A total of 22 infants had a Penrose drain inserted. Two (9%) showed improvement, 20(91%) were taken to theatre for laparotomy. Thirteen (59%) had an ileostomy performed. Seven (31.8%) had extensive bowel necrosis and subsequently died. A total 15(68.2%) out of 22 survived with initial management of Penrose drain insertion and subsequent laparotomy. Penrose drain insertion is an effective first line treatment in the pre-term infant BW < 1500g, with perforated NEC.


The application of photoelectrocatalysis in the degradation of rhodamine B in aqueous solutions: a review.
The pollution of the water environment by industrial effluents is an ongoing challenge due to the rate of industrialisation and globalisation. Photoelectrocatalysis (PEC), an electrochemical advanced oxidation process, has proven to be an effective method for removing organics from wastewater. Photoelectrocatalysis is environmentally benign, cost-effective and easy to operate. In this present review, we examine the recent progress in the removal of rhodamine B dye, a common constituent of textile effluent released into the environment, through photoelectrocatalytic degradation. We present a detailed discussion on the use of different kinds of unmodified and modified photoanodes that have been explored for the photoelectrocatalytic removal of this dye. More importantly, discussions are presented on the mechanisms and kinetics of the degradation of rhodamine B dye using these photoanodes. Hence, this review will be beneficial for researchers in developing future projects in the area of wastewater treatments through photoelectrocatalysis.


Ex utero intrapartum treatment (EXIT) for upper airway obstruction.
Improvements in the antenatal diagnosis of congenital malformations have led to increased detection of fetal airway obstructing lesions, and pediatric ear, nose, and throat surgeons are increasingly involved in these cases. This article outlines the typical range of pathology seen, the logistics in providing support for anticipated deliveries and the multidisciplinary management of complex airway cases. Traditionally, difficulty in obtaining a patent airway at delivery was a major factor in the dismal prognosis of these pregnancies. The ex utero intrapartum treatment procedure, which involves controlled partial delivery of the fetus whilst maintaining placental circulation, allows various airway maneuvers to be performed to secure the airway in a controlled fashion.


Determination of bismuth in pharmaceutical products using methyltriphenylphosphonium bromide as a molecular probe by resonance light scattering technique.
A method for the determination of bismuth in pharmaceutical products using methyltriphenylphosphonium bromide as a molecular probe based on the resonance light scattering (RLS) technique was developed. In the presence of Tween-20, bismuth reacts with a large excess of I(-) to form [BiI(4)](-), which further reacts with methyltriphenylphosphonium bromide (MTPB) to form an ion-association compound. This resulted in a significant enhancement of RLS intensity and the appearance of the corresponding RLS spectral characteristics. The enhanced RLS intensity was directly proportional to the concentration of Bi(III) in the range of 0.001-1.50 microg/ml for the system. The detection limit was 0.98 ng/ml. The characteristics of RLS spectra of the complex, the optimum conditions and the influencing factors were investigated. The method has high selectivity and was applied to the determination of Bi(III) in pharmaceutical products with satisfactory results, which were in agreement with those of the official method and atomic absorbance spectrometry (AAS).


[Nutrition Support Therapy in Critically Ill Patients].
Nutritional therapy is an elemental component of intensive care treatment. Therapeutic goals are the enteral or parenteral provision of calories, protein, electrolytes, vitamins and trace elements. Pathophysiologically, metabolism in critical illness is characterized by a catabolic stress status. This results from an underlying systemic inflammatory response and is associated with increased rate of infections, multiple organ failure and unfavourable outcome. In this article, the principles and strategies of nutrition support therapy in critically ill patients are presented, based on current guidelines.


Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells.
Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ12-PGJ2, and 15d-PGJ2, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44-/- LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML.


Hepatobiliary scintigraphy for the assessment of biliary strictures after pediatric liver transplantation.
HBS is used in the management of liver transplantation, a significant complication of which is biliary stricture. Strictures may be intraparenchymal within segments and main duct (non-anastomotic) or at the biliary-enteric anastomosis (anastomotic). Strictures are definitively diagnosed, and often managed, by PTC. This is invasive, technically challenging, and requires general anesthesia in young children. HBS may allow early detection of these complications and is non-invasive. The aim of this study was to review the scintigraphic pattern of biliary strictures using (99m)TcDISIDA HBS following pediatric orthotopic liver transplantation, and to assess its role in the diagnostic algorithm of suspected biliary strictures. All available hepatobiliary studies performed post-transplant in 101 episodes of liver transplantation in 92 pediatric patients were reviewed. Twenty-three (23%) patients had known biliary strictures. Twenty-two patients had adequate studies available for review; five had intrahepatic (non-anastomotic) strictures alone, nine had a stricture of the anastomosis alone, and eight had both intrahepatic and anastomotic strictures. HBS patterns (either segmental or global changes) correlated very highly with clinically significant biliary strictures. All patients with known strictures had abnormal HBS; hence, in patients with abnormal liver function tests post-liver transplant, a normal HBS makes strictures very unlikely. We propose that HBS can thus be used to determine if further investigation is required.


White blood cell count as a predictor of the severity of sickle cell disease during pregnancy.
Increasing epidemiological evidence implicates leukocytosis as a major risk factor for poor outcome in non-pregnant sickle cell disease (SCD) patients. The aim of this study was to investigate whether steady-state white blood cell (WBC) count can predict SCD-related problems in pregnancy. Retrospective observational study of 40 SCD pregnant women who had their antenatal care at Guy's & St Thomas' NHS Trust, London. Twenty-six women developed clinical complications related to SCD during their pregnancy (painful crisis, chest symptoms, infections, severe anaemia requiring blood transfusion, pre-eclampsia, and/or thromboembolism) and 14 remained asymptomatic. The steady-state leukocyte counts early in pregnancy were compared between the two groups and receiver operator characteristics (ROC) curve was plotted for different values of WBC. Compared to asymptomatic patients, women who developed SCD-related complications had significantly higher total WBC count [11.2 x 10(9)L(-1) (SD 3.22) versus 8 x 10(9)L(-1) (2.8), p<0.01], higher lymphocyte count [3 x 10(9)L(-1) (1.62) versus 1.6 x 10(9)L(-1) (0.65), p<0.01] and higher monocyte count [0.8 x 10(9)L(-1) (0.47) versus 0.4 x 10(9)L(-1) (0.21), p<0.01]. The neutrophil count showed a similar trend but the difference did not reach statistical significance [6.6 x 10(9)L(-1) (2.29) versus 5.7 x 10(9)L(-1) (2.15), p=0.22]. The area under the ROC curve was 74% (95% CI: 56-92). WBC count early in pregnancy was significantly higher in women who subsequently developed clinical problems related to SCD. The WBC may be used as a predictor of the severity of SCD in pregnancy.


Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele.
Sperm proteins undergo post-translational modifications, such as phosphorylation, acetylation, and ubiquitination, which in turn play a key role in determining their fertilizing ability. In the current study, we examined the sperm proteome of men with unilateral and bilateral varicocele to identify the key proteins affected by acetylation to gain an insight into the difference in the severity of affected sperm function in the latter. An LTQ-Orbitrap Elite hybrid mass spectrometer system was used to profile the sperm proteome in pooled unilateral and bilateral varicocele patients. Bioinformatics database and tools, such as UniProtKB, Ingenuity Pathway Analysis Software (IPA) and Metacore, were used to identify the differentially expressed proteins (DEPs) involved in the acetylation process. A total of 135 DEPs in the spermatozoa of unilateral and bilateral varicocele patients were found to be affected by acetylation. The majority of these DEPs found were regulated by key transcription factors such as androgen receptor, p53, and NRF2. Furthermore, the DEPs predicted to be affected by the acetylation process were associated with fertilization, acrosome reaction, mitochondrial dysfunction and oxidative stress. Aberrant expression of proteins and their differential acetylation process may affect the normal physiological functions of spermatozoa. Protein-protein interactions identified dysregulation of the proteasome complex in the bilateral varicocele group. Damage to the proteasome complex may result in aggregation of the misfolded proteins, which in turn increase sperm DNA damage and apoptosis in patients with bilateral varicocele.


Cloning, chromosomal organization and expression analysis of Neurl, the mouse homolog of Drosophila melanogaster neuralized gene.
The Drosophila neuralized (neur) gene belongs to the neurogenic group of genes involved in regulating cell-cell interactions required for neural precursor development. neur mutant phenotypes include strong overcommitment to neural fates at the expense of epidermal fates. The human neuralized homolog (NEURL) has been recently determined and found to map to chromosome 10q25.1 within the region frequently deleted in malignant astrocytomas. Because of its potential importance in developmental processes, we analyzed the structure of the mouse homolog, Neurl, and its expression pattern in embryonic tissues. Neurl activity is detected from early developmental stages in several tissues and organs including neural tissues, limbs, the skeletal system, sense organs and internal organs undergoing epithelial-mesenchymal interactions. Neurl encodes a polypeptide associated with the plasma membrane but also detected in the cytoplasm. Similarly to the Drosophila gene, mammalian neuralized may code for an important regulatory factor.


Review of the Role of Radiomics in Tumour Risk Classification and Prognosis of Cancer.
Radiomics, an emerging field in radiation therapy, is hypothesized to improve classification of tumour risk and prognosis. Despite encouraging results, there are issues of practicality and interpretation of radiomic data. This study investigates the emerging role of radiomics in tumour risk classification and prognosis of breast and prostate cancer. A literature search was conducted using predefined terms to retrieve studies related to radiomics. Studies were evaluated and selected upon meeting the criteria defined. A total of 19 relevant publications were selected from 63 publications identified. Data from studies revealed significant area under the curve (AUC) values and high discriminative power. Significant AUC values for biochemical recurrence of disease and disease-free survival were reported for prognosis. Radiomics show promising potential in discriminating tumour risk and predicting prognosis of cancer using specified features. It is an alternative to conventional predictive tools and has the ability to improve with the use of existing tools.


The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction.
Myocardial infarction (MI) dampens heart function and poses a great health risk. The class III deacetylase sirtuin 1 (SIRT1) is known to confer cardioprotection. SIRT1 expression is downregulated in the heart by a number of stress stimuli that collectively drive the pathogenesis of MI, although the underlying mechanism remains largely obscure. Here we show that in primary rat neonatal ventricular myocytes (NRVMs), ischaemic or oxidative stress leads to a rapid upregulation of SUV39H, the mammalian histone H3K9 methyltransferase, paralleling SIRT1 downregulation. Compared to wild-type littermates, SUV39H knockout mice are protected from MI. Likewise, suppression of SUV39H activity with chaetocin attenuates cardiac injury following MI. Mechanistically, SUV39H cooperates with heterochromatin protein 1 gamma (HP1γ) to catalyse H3K9 trimethylation on the SIRT1 promoter and represses SIRT1 transcription. SUV39H augments intracellular ROS levels in a SIRT1-dependent manner. Our data identify a previously unrecognized role for SUV39H linking SIRT1 trans-repression to myocardial infarction.


Allosteric Modulation of GABAA Receptors by an Anilino Enaminone in an Olfactory Center of the Mouse Brain.
In an ongoing effort to identify novel drugs that can be used as neurotherapeutic compounds, we have focused on anilino enaminones as potential anticonvulsant agents. Enaminones are organic compounds containing a conjugated system of an amine, an alkene and a ketone. Here, we review the effects of a small library of anilino enaminones on neuronal activity. Our experimental approach employs an olfactory bulb brain slice preparation using whole-cell patch-clamp recording from mitral cells in the main olfactory bulb. The main olfactory bulb is a key integrative center in the olfactory pathway. Mitral cells are the principal output neurons of the main olfactory bulb, receiving olfactory receptor neuron input at their dendrites within glomeruli, and projecting glutamatergic axons through the lateral olfactory tract to the olfactory cortex. The compounds tested are known to be effective in attenuating pentylenetetrazol (PTZ) induced convulsions in rodent models. One compound in particular, KRS-5Me-4-OCF3, evokes potent inhibition of mitral cell activity. Experiments aimed at understanding the cellular mechanism underlying the inhibitory effect revealed that KRS-5Me-4-OCF3 shifts the concentration-response curve for GABA to the left. KRS-5Me-4-OCF3 enhances GABA affinity and acts as a positive allosteric modulator of GABAA receptors. Application of a benzodiazepine site antagonist blocks the effect of KRS-5Me-4-OCF3 indicating that KRS-5Me-4-OCF3 binds at the classical benzodiazepine site to exert its pharmacological action. This anilino enaminone KRS-5Me-4-OCF3 emerges as a candidate for clinical use as an anticonvulsant agent in the battle against epileptic seizures.


Serum progesterone concentration on pregnancy test day might predict ongoing pregnancy after controlled ovarian stimulation and fresh embryo transfer.
Progesterone (P4) is essential for pregnancy. A controlled ovarian stimulation (COS) leads to a iatrogenic luteal defect that indicates a luteal phase support (LPS) at least until pregnancy test day. Some clinicians continue the LPS until week 8 or later, when P4 is mainly secreted by syncytiotrophoblast cells.Measuring serum P4 on pregnancy test day after a fresh embryo transfer could help to identify women who might benefit from prolonged LPS. In women with LPS based on P4 administered by the rectal route, P4 concentration on pregnancy test day was significantly higher in patients with ongoing pregnancy than in patients with abnormal pregnancy.This monocentric retrospective study used data on 99 consecutive cycles of COS, triggered with human chorionic gonadotropin, followed by fresh embryo transfer resulting in a positive pregnancy test (>100 IU/L) (from November 2020 to November 2022). Patients undergoing preimplantation genetic screening or with ectopic pregnancy were excluded. All patients received standard luteal phase support (i.e. micronized vaginal progesterone 600 mg per day for 15 days). The primary endpoint was P4 concentration at day 15 after oocyte retrieval (pregnancy test day) in women with ongoing pregnancy for >12 weeks and in patients with miscarriage before week 12 of pregnancy.The median P4 concentration [range] at pregnancy test day was higher in women with ongoing pregnancy than in women with miscarriage (55.9 ng/mL [11.6; 290.6] versus 18.1 ng/mL [8.3; 140.9], p = 0.002). A P4 concentration ≥16.5 ng/mL at pregnancy test day was associated with higher ongoing pregnancy rate (OR = 12.5, 95% CI 3.61 - 43.33, p <0.001). A P4 concentration ≥16.5 ng/mL at pregnancy test day was significantly associated with higher live birth rate (OR = 11.88, 95% CI 3.30-42.71, p <0.001).After COS and fresh embryo transfer, the risk of miscarriage is higher in women who discontinue luteal support after 15 days, as recommended, but with P4 concentration <16.5 ng/mL. The benefit of individualized prolonged luteal phase support should be evaluated.


Dietary animal fat in relation to ovarian cancer risk.
Food and beverage frequency questionnaires were administered to 215 white women with epithelial ovarian cancer and to 215 control women matched by age, race, and residence. Women with ovarian cancer favored foods higher in animal fats and consumed significantly greater amounts of animal fat and significantly less vegetable fat compared with control subjects. Adjusted for potential confounding due to differences between case and control subjects in weight and parity, there was a significant trend for increasing risk for ovarian cancer with increasing animal fat consumption. No major differences were noted between patients and control subjects in coffee, alcohol, and tobacco use. Dietary factors may partially explain variation in the international incidence of this disease and suggest a new pathway for its etiology.


The use of Mohs micrographic surgery (MMS) for melanoma in situ (MIS) of the trunk and proximal extremities.
Evaluation of the entire surgical margin results in high rates of complete excision, low local recurrence rates, and maximal tissue conservation. Although well recognized for melanoma of the head and neck, few studies have focused exclusively on the trunk and proximal extremities. We sought to evaluate the efficacy of Mohs micrographic surgery for melanoma in situ (MIS) of the trunk and proximal extremities, and determine adequate excision margins for MIS when total margin evaluation is not used. Long-term outcomes in 882 cases of MIS treated with Mohs micrographic surgery were analyzed and compared with historical controls. Rates of complete excision were determined for increasing surgical margin intervals. One local recurrence occurred in our cohort (0.1%). Only 83% of MIS were excised with a 6-mm margin. Margins of 9 mm were needed to excise 97% of MIS, statistically equivalent to thin melanomas. We used a nonrandomized, single-institution, retrospective design. Mohs micrographic surgery may cure the 17% of MIS that exceed traditional excision margins of 5 mm and is a valuable option for these patients. Surgical margins of at least 0.9 cm should be considered for MIS of the trunk and extremities when total margin evaluation is not used.