In ineffective esophageal motility, failed swallows are more functionally relevant than weak swallows.
Esophageal pressure topography (EPT) diagnosis of ineffective esophageal motility (IEM) can be non-specific with unclear clinical significance. To determine whether peristaltic vigor or lower esophageal sphincter (LES) integrity is associated with poor clearance and acid reflux in IEM. Bolus clearance on high-resolution impedance manometry (HRIM) and available reflux studies in patients with IEM were retrospectively reviewed. Bolus clearance was assessed using both line tracing and colored contour methods on HRIM. EPT parameters, bolus clearance, and acid reflux variables were explored. Eighty-eight patients with IEM were included. Bolus clearance occurred in 71% of all swallows, and 55.7% of patients had complete bolus transit (CBT, bolus clearance in ≥80% of swallows). Bolus clearance was impaired in swallows with distal contractile integral (DCI) <100 mmHg•cm•s compared to DCI 100-450 (0.43 vs 0.79, P < .0001). A cutoff at DCI 100 mmHg•cm•s was associated with clearance with an accuracy of 76% compared to 49% at DCI 450 (P = .0001 for both). A median DCI <100 was associated with a higher Eckardt score (9 vs 3, P = .03), and on reflux testing available in 47 patients, with abnormal acid exposure time (P = .002). Peristaltic reserve (PR) defined as (DCI of multiple rapid swallow/median DCI of wet swallows), integrated relaxation pressure, and resting lower esophageal sphincter pressure were not associated with clearance or acid exposure. Failed peristalsis, as defined by DCI <100 mmHg•cm•s, is associated with impaired bolus clearance and more severe dysphagia in IEM, and likely abnormal acid exposure.


MicroRNAs in endothelial cell homeostasis and vascular disease.
Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with several aspects of vascular dysfunction. MiRNAs have been found to be critical modulators of endothelial homeostasis. The dysregulation of miRNAs has been linked to endothelial dysfunction and the development and progression of vascular disease which and open new opportunities of using miRNAs as potential therapeutic targets for vascular disease. Further determination of miRNA regulatory circuits and defining miRNAs-specific target genes remains key to future miRNA-based therapeutic applications toward vascular disease prevention. Many new and unanticipated roles of miRNAs in the control of endothelial functions will assist clinicians and researchers in developing potential therapeutic applications.


Antivirals for Respiratory Viral Infections: Problems and Prospects.
In the past two decades, several newly emerging and reemerging viral respiratory pathogens including several influenza viruses (avian influenza and pandemic influenza), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV), have continued to challenge medical and public health systems. Thereafter, the development of cost-effective, broad-spectrum antiviral agents is the urgent mission of both virologists and pharmacologists. Current antiviral developments have focused targets on viral entry, replication, release, and intercellular pathways essential for viral life cycle. Here, we review the current literature on challenges and prospects in the development of these antivirals.


Preschool teacher attachment and attention skills.
Attention underlies and energizes all cognitive and behavioral activities. Many studies showed that the quality of child attachment (both to parental and non parental figures) influences cognitive functions and attention. This study aimed to investigate the relationships among attachment to preschool teachers and attention in a sample of preschoolers. In particular, the study analyzed whether child attachment security to preschool teachers influences the different aspects of their attention skills. In addition, gender- and age-related differences in attention and teacher attachment were explored. Research was conducted using two standardized instruments: the Attention and Concentration Battery, and the Attachment Q Sort. Participants were 279 children (147 male, 132 female) who attended two preschools in a town in Southern Italy. Descriptive analyses, t-tests analyses, and correlation and regression analyses were carried out. Findings highlighted several interesting points concerning the relationships that occur among attachment to preschool teachers and attention. Children with secure attachments presented higher reaction time and better auditory, visual, and visual spatial selectivity and maintenance.


Posterior Quadratus Lumborum Block for Labor Analgesia: A Case Report.
Neuraxial analgesia has been established as the standard of care for labor analgesia. However, patients presenting with coagulopathy require anesthesiologists to explore alternate analgesic techniques. Systemic opioids may result in neonatal respiratory depression, and inhaled nitrous oxide may lead to nausea, vomiting, and over sedation and may not be readily available in all labor and delivery units. In this case report, we describe a case where posterior quadratus lumborum blocks provided effective analgesia in a parturient with Hemophilia A during the first stage of labor.


[Screening for mental distress symptoms among Ukrainian refugees in an initial reception center in Baden-Württemberg].
Millions of people are fleeing the war in Ukraine. Stressors associated with flight can have a massive impact on mental health. The aim of the present study was to perform a low-threshold screening for mental distress symptoms among Ukrainian refugees in an initial reception center in Baden-Württemberg. At the initial reception center in Heidelberg Ukrainian refugees were interviewed about psychological distress during consultations with medical care providers, using four screening questionnaires (PC-PTSD-5, PHQ-9, GAD-7, stress thermometer) in Ukrainian or Russian language, and further sociodemographic data and data about the refugees' background were collected. More than 90% of the N = 36 respondents reported that they had experienced war, 55.6% reached the cut-off score for post-traumatic stress disorder. One fourth of the participants reached cut-off scores for depression and more than 30% for generalized anxiety disorder. The majority of respondents had relatives living in embattled cities, and in over 36% close relatives were currently deployed in war. In the group comparison there was no significant correlation of symptom burden with the family background situation. In line with the existing literature, many of the participants showed signs of mental distress. Potentially affected persons can be identified using low-threshold screening questionnaires. Adequate care for mentally stressed refugees according to their needs should be established to facilitate integration. Due to the known high prevalence of mental distress, refugees should be screened for mental distress symptoms at a low-threshold level to identify affected individuals. The psychosocial situation of Ukrainian refugees should be considered at an early stage in medical care.


Protective effect of ultra low molecular weight heparin on glutamate-induced apoptosis in cortical cells.
To investigate the effect of ultra low molecular weight heparin (ULMWH) on glutamate induced apoptosis in rat cortical cells and to explore the possible mechanisms. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was first analyzed with Hoechst 33258 and then confirmed by DNA fragmentation. The concentration of free intracellular calcium ([Ca(2+)](i)) was determined with fura-2/AM fluorometry. The expression of Bcl-2 family protein and caspase-3 were evaluated with Western blot. Typical apoptotic morphological change in rat cortical cells treated with 100 micromol/L glutamate for 24h was detected by Hoechst 33258 staining, which was then confirmed by the DNA ladder of agarose gel electrophoresis. The apoptotic rate of the glutamate treated cells was up to 33.21%, and 24 h of treatment with glutamate increased [Ca(2+)](i), down-regulated Bcl-2 expression, up-regulated Bax expression, and increased caspase-3 activation in rat cortical cells. Our research demonstrated that ULMWH pretreatment can prevent the glutamate-induced apoptosis, attenuate the increase of [Ca(2+)](i) not only in medium containing Ca(2+) but also in Ca(2+)-free medium, up-regulate the expression of Bcl-2, down-regulate the expression of Bax, and decrease caspase-3 activation. ULMWH has neuroprotective capacity to antagonize glutamate-induced apoptosis in cortical cells, through decrease of Ca(2+) release and modulation of apoptotic processes.


Description of acute ozone response as a function of exposure rate and total inhaled dose.
The magnitude of respiratory responses to short-term ozone exposure is known to be a function of the exposure variables concentration (C), duration of exposure (T), and minute ventilation (VE) during exposure. The purpose of this study was to identify a mathematical model that described ozone-induced mean decrements in forced expiratory volume in 1 s (FEV1) as a function of exposure rate (C x VE) and total inhaled dose (C x VE x T). Three hundred seventy-four young male nonsmokers participated in 504 exposures to several concentrations of ozone for 2 or 6.6 h. Mean percent change in FEV1 was calculated for each hour of exposure and was fit to the exposure variables by use of nonlinear models. We identified a general sigmoid-shaped model that well described the observed mean response in terms of exposure rate and total inhaled dose over a wide range of C and T. By fixing the value of a single parameter, this model reduces to a simpler form, which was adequate for description of responses over narrower ranges of exposure conditions. We concluded that the observed mean responses to short-term ozone exposure were adequately described by the nonlinear models identified in this study and that models of this form may be useful for description of responses over a wide range of C and T.


TeamSTEPPS and patient safety in healthcare.
Communication problems in healthcare are considered to be a leading cause of medical errors and often the root cause of sentinel events. This article will review the implementation of TeamSTEPPS in the two large health systems. The challenges in the implementation process, the successes, failures, and the obstacles will be discussed. Comparisons between the systems as well as lessons learned after implementation will be reviewed to enable hospitals and health systems to implement and sustain a successful TeamSTEPPS program.


Effect of immunization of sexually immature pullets against poly-alpha-L-glutamic acid on long-term fertility.
Poly-alpha-L-glutamic acid (PGA) is a polypeptide synthesized within the upper oviduct and uterovaginal junction of the hen. Sexually immature pullets were immunized against PGA. These virgin pullets, and immunized and non-immunized controls, were inseminated at 25 weeks of age and then monthly throughout a 30-week egg production interval. While birds immunized against PGA were free of PGA as evidenced by an absence of immunoprecipitation when rabbit anti-PGA serum was overlayed with oviduct extract, immunization had no effect on long-term fertility and therefore is unlikely to have an immunosuppressive or antigen-masking biological role with respect to spermatozoa. We suggest instead that PGA could act as a calcium binding protein.


Crosstalk and the evolvability of intracellular communication.
Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks.


Identification of distinct N-terminal truncated forms of prion protein in different Creutzfeldt-Jakob disease subtypes.
In prion diseases, the cellular prion protein (PrP(C)) is converted to an insoluble and protease-resistant abnormal isoform termed PrP(Sc). In different prion strains, PrP(Sc) shows distinct sites of endogenous or exogenous proteolysis generating a core fragment named PrP27-30. Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, clinically presents with a variety of neurological signs. As yet, the clinical variability observed in sCJD has not been fully explained by molecular studies relating two major types of PrP27-30 with unglycosylated peptides of 21 (type 1) and 19 kDa (type 2) and the amino acid methionine or valine at position 129. Recently, smaller C-terminal fragments migrating at 12 and 13 kDa have been detected in different sCJD phenotypes, but their significance remains unclear. By using two-dimensional immunoblot with anti-PrP antibodies, we identified two novel groups of protease-resistant PrP fragments in sCJD brain tissues. All sCJD cases with type 1 PrP27-30, in addition to MM subjects with type 2 PrP27-30, were characterized by the presence of unglycosylated PrP fragments of 16-17 kDa. Conversely, brain homogenates from patients VV and MV with type 2 PrP27-30 contained fully glycosylated PrP fragments, which after deglycosylation migrated at 17.5-18 kDa. Interestingly, PrP species of 17.5-18 kDa matched deglycosylated forms of the C1 PrP(C) fragment and were associated with tissue PrP deposition as plaque-like aggregates or amyloid plaques. These data show the presence of multiple PrP(Sc) conformations in sCJD and, in addition, shed new light on the correlation between sCJD phenotypes and disease-associated PrP molecules.


Neurological deterioration as a result of improper neck position detected by intraoperative neurophysiological monitoring in a cervical stenosis patient: A case report.
Intraoperative neurophysiological monitoring (IONM) is widely used in spinal surgeries to prevent iatrogenic spinal cord injury (SCI). Most surgeons focus on avoiding neurological compromise intraoperatively, while ignoring the possibility of nerve damage preoperatively, such as neck positioning. Thus, this study aims to report a case with transient neurological deterioration due to improper neck position detected by IONM during cervical surgery. A 63-year-old male patient had been suffering from hypoesthesia of the upper and lower extremities for three years. Severe cervical stenosis (C5-C7) and cervical ossification of a posterior longitudinal ligament. The cervical stenosis patient underwent an anterior cervical corpectomy decompression and fusion (ACDF) surgery with the assistance of IONM. When the lesion segment was exposed, the SSEP and MEP suddenly elicited difficulty indicating that the patient may have developed SCI. All the technical causes of IONM events were eliminated, and the surgeon suspended operation immediately and suspected that the IONM alerts were caused by cervical SCI due to the improper position of the neck. Subsequently, the surgeon repositioned the neck of the patient by using a thinner shoulders pad. At the end of the operation, the MEP and SSEP signals gradually returned to 75% and 80% of the baseline, respectively. Postoperatively, the muscle strength of bilateral biceps decreased from grade IV to grade III. Besides, the sensory disturbance of both upper extremities aggravated. However, the muscle power and hypoesthesia were significantly improved after three months of neurotrophic therapy and rehabilitation training, and no complications of nerve injury were found at the last follow-up visit. IONM, consisting of SSEP and MEP, should be applied throughout ACDF surgery from the neck positioning to suture incisions. Besides, in the ward 1to 2 days before operation, it is necessary for conscious patients with severe cervical stenosis to simulate the intraoperative neck position. If the conscious patients present signs of nerve damage, they can adjust the neck position immediately until the neurological symptoms relieve. Therefore, intraoperatively, the unconscious patient can be placed in a neck position that was confirmed preoperatively to prevent SCI.


Synergizing Spatial Confinement and Dual-Metal Catalysis to Boost Sulfur Kinetics in Lithium-Sulfur Batteries.
Sluggish kinetics and parasitic shuttling reactions severely impede lithium-sulfur (Li-S) battery operation; resolving these issues can enhance the capacity retention and cyclability of Li-S cells. Therefore, an effective strategy featuring core-shell-structured Co/Ni bimetal-doped metal-organic framework (MOF)/sulfur nanoparticles is reported herein for addressing these problems; this approach offers unprecedented spatial confinement and abundant catalytic sites by encapsulating sulfur within an ordered architecture. The protective shells exhibit long-term stability, ion screening, high lithium-polysulfide adsorption capability, and decent multistep catalytic conversion. Additionally, the delocalized electrons of the MOF endow the cathodes with superior electron/lithium-ion transfer ability. Via multiple physicochemical and theoretical analysis, the resulting synergistic interactions are proved to significantly promote interfacial charge-transfer kinetics, facilitate sulfur conversion dynamics, and inhibit shuttling. The assembled Li-S batteries deliver a stable, highly reversible capacity with marginal decay (0.075% per cycle) for 400 cycles at 0.2 C, a pouch-cell areal capacity of 3.8 mAh cm-2 for 200 cycles under a high sulfur loading, as well as remarkably improved pouch-cell performance.


DNA-dependent RNA polymerase C from Xenopus laevis ovaries. Ability to transcribe intact double-stranded DNA.
DNA-dependent RNA polymerase C, partially purified from Xenopus laevis ovaries, has been resolved by DEAE-Sephadex chromatography in two forms, eluting at 0.2 M and 0.3 M ammonium sulfate, respectively. Both are sensitive to high concentrations of alpha-amanitin (200 mug/ml). Their ionic strength dependence and divalent cation requirements are indistinguishable. Quantitatively, RNA polymerase C represents the major form of RNA polymerase activity solubilized from the ovaries. Both RNA polymerases C are able to transcribe efficiently either high-molecular-weight Xenopus DNA or intact adenovirus DNA, as compared to nicked DNA. In contrast, RNA polymerase A has little activity on an intact DNA template. The salt dependence of the RNA polymerases C activity is different on the two kinds of template. Nicked DNA is efficiently transcribed up to a salt concentration of 100 mM ammonium sulfate. On intact DNA, optimal transcription is obtained at 40 mM ammonium sulfate and is inhibited by higher salt concentrations.


Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.
Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed in preclinical and clinical studies. The subtle sex differences observed in the behavioral aspects of PSUD may be associated with differences in the neurochemistry of the dopaminergic system between sexes. Preclinically, psychostimulants have been shown to increase synaptic dopamine (DA) levels and may downregulate the dopamine transporter (DAT). This effect is greatest in females during the high estradiol phase of the estrous cycle. Interestingly, women have been shown to be more likely to begin drug use at younger ages and report higher levels of desire to use cocaine than males. Even though there is currently no FDA-approved medication, modafinil, a DAT inhibitor approved for use in the treatment of narcolepsy and sleep disorders, has shown promise in the treatment of PSUD among specific populations of affected individuals. In this review, we highlight the therapeutic potential of modafinil and other atypical DAT inhibitors focusing on the lack of sex differences in the actions of these agents.


The type 1 diabetes susceptibility gene SUMO4 at IDDM5 is not associated with susceptibility to rheumatoid arthritis or juvenile idiopathic arthritis.
Linkage and association of rheumatoid arthritis (RA) and rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) has previously been demonstrated to the type 1 diabetes (T1D) locus, IDDM5, on chromosome 6q25. An association of a methionine-to-valine polymorphism (rs237025, 163A --> G, M55V) in the SUMO4 gene within IDDM5 has recently been described in T1D. The objective of this study was to test the hypothesis that SUMO4 is a general autoimmune susceptibility gene by investigating whether the SUMO4 polymorphism is associated with RA and/or JIA. The SUMO4 SNP was genotyped in 875 RA patients, 668 JIA patients and 484 healthy controls using a TaqMan allelic discrimination assay. Allele and genotype frequencies were compared between cases and controls using the chi2 test. Analyses were also carried out with RA patients stratified by gender, age at onset, RF status, the presence of erosive disease and shared epitope status, while JIA patients were stratified by their International League of Associations for Rheumatology (ILAR) subgroup. No deviation from Hardy-Weinberg equilibrium was detected in either set of cases or controls. No association was observed between rs237025 and RA (chi2 = 0.17, P = 0.93), or with any RA subset. Similarly, there was no association between this SNP and JIA (chi2 = 0.21, P = 0.90), or with any ILAR subgroup. The M55V substitution in the SUMO4 gene is not associated with susceptibility to RA or JIA in the UK population studied. However, other candidate genes mapping within IDDM5 remain to be investigated.


CNN Hardware Accelerator for Real-Time Bearing Fault Diagnosis.
This paper introduces a one-dimensional convolutional neural network (CNN) hardware accelerator. It is crafted to conduct real-time assessments of bearing conditions using economical hardware components, implemented on a field-programmable gate array evaluation platform, negating the necessity to transfer data to a cloud-based server. The adoption of the down-sampling technique augments the visible time span of the signal in an image, thereby enhancing the accuracy of the bearing condition diagnosis. Furthermore, the proposed method of quaternary quantization enhances precision and shrinks the memory demand for the neural network model by an impressive 89%. Provided that the current signal data sampling rate stands at 64 K samples/s, the proposed design can accomplish real-time fault diagnosis at a clock frequency of 100 MHz. Impressively, the response duration of the proposed CNN hardware system is a mere 0.28 s, with the fault diagnosis precision reaching a remarkable 96.37%.


Lymphatic innervation.
Bovine mesenteric lymphatic vessels have nerves in their walls which in response to field stimulation cause an increase in frequency of spontaneous lymphatic contractions and this could be blocked by alpha-antagonists. When vessels were loaded with [3H]-noradrenaline, 3H-efflux was increased in response to field stimulation and this was potentiated by alpha 2-antagonists and depressed by alpha 2-agonists. Electrical activity in these vessels consisted of a single action potential which preceded each contraction. Mean resting potential was -61 mV +/- 5.7 (SD). Stimulation of postsynaptic alpha-receptors caused a depolarization accompanied by a decrease in membrane conductance while beta-receptor stimulation had the opposite effect. Lymphatic noradrenergic nerves appear to have a role in the living animal since stimulation of the sympathetic chain in anaesthetized sheep increased popliteal efferent lymph flow and this could be blocked by alpha-adrenergic blockers.


WDS versus silicon drift detector EDS: a case report for the comparison of quantitative chemical analyses of natural silicate minerals.
Electron probe microanalysis (EPMA) is an essential analytical approach to determine elemental concentrations of various solid specimens quantitatively in mineralogical, petrological and materials research. Either wavelength dispersive X-ray (WDS) or energy dispersive X-ray (EDS) spectrometric techniques can collect the characteristic X-rays generated from each element in the specimen by an incident electron beam in order to define chemical constituents. Although WDS has been the preferred technique because of its higher spectral resolution and ability to detect trace elements, new generation EDS systems with silicon drift detectors (SDD), equipped with thin windows and integrated digital processing electronics, are claimed to approach the WDS throughput. In this study, we compared the analytical capability of a SDD EDS system with respect to WDS equipped systems on natural silicate minerals. For this purpose, natural rock samples, in which the silicate minerals present had already been analysed by various WDS systems, were chosen to compare these results with the ones acquired with a SDD EDS system. SDD EDS yielded satisfactory results for major elements (Na, Mg, Al, Si, K, Ca, Ti, Mn and Fe) compared with the results of the same minerals obtained by various WDS systems.


Monte Carlo modeling of polarized light propagation: Stokes vs. Jones. Part II.
In this second part of our comparative study inspecting the (dis)similarities between "Stokes" and "Jones," we present simulation results yielded by two independent Monte Carlo programs: (i) one developed in Bern with the Jones formalism and (ii) the other implemented in Ulm with the Stokes notation. The simulated polarimetric experiments involve suspensions of polystyrene spheres with varying size. Reflection and refraction at the sample/air interfaces are also considered. Both programs yield identical results when propagating pure polarization states, yet, with unpolarized illumination, second order statistical differences appear, thereby highlighting the pre-averaged nature of the Stokes parameters. This study serves as a validation for both programs and clarifies the misleading belief according to which "Jones cannot treat depolarizing effects."


Propagation of optical vortices in a nonlinear atomic medium with a photonic band gap.
We experimentally generate a vortex beam through a four-wave mixing (FWM) process after satisfying the phase-matching condition in a rubidium atomic vapor cell with a photonic band gap (PBG) structure. The observed FWM vortex can also be viewed as the reflected part of the launched probe vortex from the PBG. Further, we investigate the propagation behaviors, including the spatial shift and splitting of the probe and FWM vortices in the medium with enhanced Kerr nonlinearity induced by electromagnetically induced transparency. This Letter can be useful for better understanding and manipulating the applications involving the interactions between optical vortices and the medium.


Acceptability of a reusable insulin pen, HumaPen Ergo, by patients with type 1 and type 2 diabetes.
A reusable insulin pen (HumaPen Ergo) was tested for patient acceptability and safety in two multinational studies involving a total of 230 patients with either type 1 (27%) or type 2 (73%) diabetes. Prior to the studies, all patients used other insulin injection pen models. During the 5-7-week studies, the acceptability of HumaPen Ergo was assessed with a questionnaire which was issued to all patients. The HumaPen Ergo was considered easy/very easy with respect to learning to use (97%), reading dose numbers (95%) and correcting dose mistakes (97%), and 62% considered it easy/very easy to hold during use. HumaPen Ergo features considered easier/much easier compared to the previously used model of pen were ease of correcting dose (Study 1/Study 2: 89%/93%), ease of reading the dose number (77%/61 %) and ease of changing cartridge (54%/68%). At the end of the studies the majority of patients (60%/69%) said that they would continue to use HumaPen Ergo and would recommend it to other patients, even though they had expressed satisfaction with the pen that they had used previously. Health-care professionals evaluated HumaPen Ergo according to the same criteria as the patients and said that they would recommend the HumaPen Ergo owing to ease of dialling back without wasting insulin (80%) and reading dose numbers (74%). The HumaPen Ergo was well accepted by both patients and health-care professionals and provides an important tool to combat the trauma and inconvenience associated with insulin self-injection.


The cell lineage of the polyplacophoran, Chaetopleura apiculata: variation in the spiralian program and implications for molluscan evolution.
Polyplacophorans, or chitons, are an important group of molluscs, which are argued to have retained many plesiomorphic features of the molluscan body plan. Polyplacophoran trochophore larvae posses several features that are distinctly different from those of their sister trochozoan taxa, including modifications of the ciliated prototrochal cells, the postrochal position of the larval eyes or ocelli, epidermal calcareous spicules, and a collection of serially reiterated epidermal shell plates. Despite these differences, chitons demonstrate a canonical pattern of equal spiral cleavage shared by other spiralian phyla that permits the identification of homologous cells across this animal clade. Cell lineage analysis using intracellular labeling on one chiton species, Chaetopleura apiculata, shows that the ocelli are generated from different lineal precursors (second-quartet micromeres: 2a, 2c) compared to those in all other spiralians studied to date (first-quartet micromeres: 1a, 1c). This situation implies that significant changes have also occurred in terms of the inductive interactions that control eye development in the spiralians. Although radical departures from the spiralian developmental program are seen in some molluscs (i.e., cephalopods), the findings presented here indicate that important changes can occur even within the highly constrained framework of the spiral cleavage program. Among spiralians, variation has been reported for the origin of the anterior, sensory, apical organ, which arises from the 1c and 1d micromeres in C. apiculata. The prototroch of C. apiculata consists of two to three irregular rows of ciliated cells but arise from 1q and 2q daughters, similar to that of Ischnochiton rissoi, as well as the gastropod, Patella vulgata. Despite certain early claims, there is no supporting evidence that any of the shell plates arise pretrochally in C. apiculata. The first seven of eight definitive shell plates that arise in the larva originate from shell secreting grooves in the postrochal region (derived from 2c, 2d, 3d). Earlier descriptions indicate that the eighth plate arises later at metamorphosis, and as this is formed posteriorly, it too forms in the postrochal region. On the other hand, epidermal spicules originate from both pretrochal and postrochal cells (1a,1d, 2a, 2c, 3c, 3d). The significance of these observations is discussed in light of various hypotheses concerning the origin of the conchiferan shell. This study reveals conservation, as well as evolutionary novelty, in the assignment of specific cell fates in the spiralians.


Single-crystalline germanium nanomembrane photodetectors on foreign nanocavities.
Miniaturization of optoelectronic devices offers tremendous performance gain. As the volume of photoactive material decreases, optoelectronic performance improves, including the operation speed, the signal-to-noise ratio, and the internal quantum efficiency. Over the past decades, researchers have managed to reduce the volume of photoactive materials in solar cells and photodetectors by orders of magnitude. However, two issues arise when one continues to thin down the photoactive layers to the nanometer scale (for example, <50 nm). First, light-matter interaction becomes weak, resulting in incomplete photon absorption and low quantum efficiency. Second, it is difficult to obtain ultrathin materials with single-crystalline quality. We introduce a method to overcome these two challenges simultaneously. It uses conventional bulk semiconductor wafers, such as Si, Ge, and GaAs, to realize single-crystalline films on foreign substrates that are designed for enhanced light-matter interaction. We use a high-yield and high-throughput method to demonstrate nanometer-thin photodetectors with significantly enhanced light absorption based on nanocavity interference mechanism. These single-crystalline nanomembrane photodetectors also exhibit unique optoelectronic properties, such as the strong field effect and spectral selectivity.


Energy drinks: a narrative review of their physiological and pathological effects.
The consumption of energy drinks (Edks) has increased significantly in past years, with a growing market that is estimated to reach $61 billion by 2021 worldwide. Several studies demonstrated the physiological and pathological effects of these substances contained in Edks. The most common ingredient contained in Edks is caffeine, which is commonly mixed with taurine, and B-group vitamins. Scientific evidence of potentially serious adverse health effects are known, but it would be better to acquire more information regarding these beverages. We systematically checked Medical literature on MEDLINE-Pubmed from inception to January 2020 to find studies and reports on Edks and adverse events. Edks consumption is specially related to cardiovascular effects as malignant arrhythmias. We found a significant focus on arrhythmogenic risk in patients affected by long QT syndrome or other predisposing conditions for QT elongation. Other pathological effects are known as gastrointestinal, vascular and neurological disorders. Edks, as well as all caffeinated beverages, should be taken with caution or avoided in select populations, such as patients suffering from cardiovascular or neurological illnesses; their use can unmask a sleepy life-threatening disease.


Long-term systemic antibiotics and surgical treatment can be an effective treatment option for retrobulbar abscesses in rabbits (Oryctolagus cuniculus): 21 cases (2011-2022).
To characterize the epidemiologic features of rabbits with retrobulbar abscesses, including the clinical signs, diagnosis, treatment, and outcome. 21 client-owned rabbits. The medical record database of a veterinary teaching hospital was searched from 2011 to 2022 for records of rabbits diagnosed with retrobulbar abscesses by CT. Data reviewed included age, breed, presenting complaint, association with an odontogenic infection, aerobic and anaerobic culture results, treatment, and outcome. The primary presenting complaint was exophthalmos (19/21 [90%]). Most cases (15/21 [71%]) were associated with an odontogenic infection. Dental disease, not associated with a retrobulbar abscess (14/21 [67%]), was a common comorbidity on CT. The most common aerobic and anaerobic isolates were Streptococcus intermedius (5/12 [42%]) and Fusobacterium nucleatum (2/12 [17%]), respectively. Surgical treatment combined with long-term systemic antibiotic therapy was performed in 9 of 21 (43%) cases. It included intraoral tooth extraction (4/9 [44%]) versus extraoral peribulbar abscess lancing with either abscess packing with antibiotic-soaked gauze (3/9 [33%]) or surgical abscess debridement (2/9 [22%]). Resolution of the clinical signs with no recurrence for at least 6 months occurred in 7 of 9 (78%) surgically treated cases. Medical treatment with long-term systemic antibiotic therapy was performed in 4 of 21 (19%) cases, and 3 of 4 (75%) resolved. Due to poor prognosis or financial concerns, euthanasia was performed or recommended in 8 of 21 (38%) cases. On the basis of the data from this study, retrobulbar abscesses in rabbits carry a guarded prognosis. When intraoral and extraoral surgical treatment options combined with systemic antibiotic therapy were used, it resolved clinical disease in most cases.


Purification and biochemical characterization of a novel thermostable protease from the oyster mushroom Pleurotus sajor-caju strain CTM10057 with industrial interest.
Proteases are hydrolytic enzymes that catalyze peptide linkage cleavage reactions at the level of proteins and peptides with different degrees of specificity. This group draws the attention of industry. More than one protease in three is a serine protease. Classically, they are active at neutral to alkaline pH. The serine proteases are researched for industrial uses, especially detergents. They are the most commercially available enzyme group in the world market. Overall, fungi produced extracellular proteases, easily separated from mycelium by filtration. A new basidiomycete fungus CTM10057, a hyperproducer of a novel protease (10,500 U/mL), was identified as Pleurotus sajor-caju (oyster mushroom). The enzyme, called SPPS, was purified to homogeneity by heat-treatment (80 °C for 20 min) followed by ammonium sulfate precipitation (35-55%)-dialysis, then UNO Q-6 FPLC ion-exchange chromatography and finally HPLC-ZORBAX PSM 300 HPSEC gel filtration chromatography, and submitted to biochemical characterization assays. The molecular mass was estimated to be 65 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Native-PAGE, casein-zymography, and size exclusion by HPLC. A high homology with mushroom proteases was displayed by the first 26 amino-acid residues of the NH2-terminal aminoacid sequence. Phenylmethanesulfonyl fluoride (PMSF) and diiodopropyl fluorophosphates (DFP) strongly inhibit SPPS, revealing that it is a member of the serine-proteases family. The pH and temperature optima were 9.5 and 70 °C, respectively. Interestingly, SPPS possesses the most elevated hydrolysis level and catalytic efficiency in comparison with SPTC, Flavourzyme® 500 L, and Thermolysin type X proteases. More remarkably, a high tolerance towards organic solvent tolerance was exhibited by SPPS, together with considerable detergent stability compared to the commercial proteases Thermolysin type X and Flavourzyme® 500 L, respectively. This proves the excellent proprieties characterizing SPPS, making it a potential candidate for industrial applications especially detergent formulations.


Post-gastrectomy osteopenia in the rat: bone structure is preserved by retaining 10%-30% of the oxyntic gland area.
The acid-producing part of the rat stomach (fundus) is rich in endocrine cells, i.e. ECL cells and A-like cells. The ECL cells operate under gastrin control and manufacture histamine, the chromogranin-derived peptide pancreastatin and an unidentified peptide hormone. The A-like cells produce ghrelin, a newly discovered growth hormone-releasing hormone. Surgical removal of the entire glandular stomach (gastrectomy, Gx) or the acid-producing part (fundectomy, Fx) causes osteopenia, which is striking in the calvaria. We speculate that the osteopenia develops after surgical removal of the fundus, because the fundus hosts agents that preserve bone. This study examines how much of the fundus is needed to preserve normal skull bone. Increasing portions of the fundus were resected surgically. The serum gastrin, ghrelin and pancreastatin concentrations were measured. The rats were killed after 10 weeks and the calvariae were subjected to transillumination analysis and quantitative histomorphometry. Fx elevated serum gastrin in proportion to the amount of fundus resected, i.e., the more fundus that was resected, the higher the serum gastrin concentration. Serum ghrelin and pancreastatin concentrations were reduced proportionally to the amount of fundus resected. In rats subjected to 90% or 100% Fx, the calvariae displayed the anticipated pattern of bone loss. No bone loss was seen when 70% or less of the fundus was resected. The results of the present study indicate that 10%-30% of the fundic mucosa is needed to preserve bone. The Gx/Fx-evoked osteopenia may be explained by hormonal deficiency caused by surgically eliminating or diminishing one of the endocrine cell populations in the fundic mucosa.


Acute pancreatitis due to a duodenal ulcer.
Duodenal ulcers and acute pancreatitis are two of the most commonly encountered gastrointestinal diseases among the general population. However, duodenal ulcer-induced pancreatitis is very rarely reported worldwide. This report elaborates on a distinct medical treatment that contributes to partial or complete treatment of acute pancreatitis induced by a duodenal ulcer scar.


Anesthesia of the geriatric equine.
Advancements in veterinary medicine have resulted in an increased number of geriatric horses being presented for medical or surgical procedures that require general anesthesia. Due to the physiological changes associated with aging and the likelihood of concurrent disease conditions, the geriatric equine is at an increased risk during anesthesia. The main physiological changes associated with aging, and their impact on anesthesia, are discussed in this review.


Effectiveness and Safety of Sleeve Gastrectomy, Gastric Bypass, and Adjustable Gastric Banding in Morbidly Obese Patients: a Multicenter, Retrospective, Matched Cohort Study.
Laparoscopic adjustable gastric band (LAGB), laparoscopic sleeve gastrectomy (LSG), and laparoscopic Roux-en-Y gastric bypass (LRYGB) are the most performed procedures worldwide (92 %) nowadays. However, comparative clinical trials are scarce in literature. The objective of this study was to compare the effectiveness and safety of the three most performed bariatric procedures. A multicenter, retrospective, matched cohort study was conducted. Patients were eligible for analysis when a primary procedure was performed between 2007 and 2010 in one of the two specialized bariatric centers. Primary outcome was weight loss, expressed in the percentage excess weight loss (%EWL). Secondary outcome parameters are hospital stay, complication rate, and revisional surgery. In total, 735 patients, 245 in each group, were included for analysis. The groups were comparable for age and gender after matching. Mean postoperative follow-up was 3.1 ± 1.2 years. LAGB patients showed less %EWL compared to LSG and LRYGB at all postoperative follow-up visits. LRYGB showed a %EWL of 71 ± 20 % compared to LSG (76 ± 23 %; p=0.008) after 1-year follow-up; thereafter, no significant difference was observed. After 3 years of follow-up, LAGB showed a higher complication rate compared to LSG and LRYGB (p<0.05). Revisional surgery after LAGB was needed in 21 %, while 9 % of the LSG underwent conversion to RYGB. LRYGB is a safe and effective treatment in morbid obese patients with good long-term outcomes. LSG seems to be an appropriate alternative as a definitive procedure, in terms of weight reduction and complication rate. LAGB is inferior to both LRYGB and LSG.


Short-time least squares spectral analysis of pass-by noise in water from a rigid inflatable boat.
This paper investigates least squares spectral analysis as a tool to analyze non-stationary signals from pass-by noise measurements in water. The spectral analysis involves successive least squares fitting of a finite Fourier series to approximate the observation in a piecewise manner. The least squares spectral analysis is used to search the signals for first- and second-order periodicity as well as the presence of fundamental periodicity. A first-order analysis reveals line components in the signals, whereas a second-order analysis reveals periodic amplitude modulations. Analysis with a higher-order finite Fourier series reveals harmonic structures in the signals. The main contribution of this paper is the model of a magnitude-squared cosine wave which can be used to analyze second-order periodicity. The developed short-time least squares spectral analysis is illustrated on noise radiated from a rigid inflatable boat in shallow water.


Neuronavigation in interventional MR imaging. Frameless stereotaxy.
The main thrust of diagnostic MR imaging is to discern normal and pathologic patient morphology and function. Intraprocedural imaging, however, serves a different goal: to furnish the surgeon or interventionalist with updates on intraoperative changes and how they may modify preintervention data. Although researchers have not established whether MR image-guided therapy can improve clinical outcomes and reduce complication rates definitively, the intraoperative and preoperative data generated will improve the ability of every neurosurgeon to navigate in the surgical field more accurately.


Naturally Occurring Cardenolides Affecting Schistosoma mansoni.
Schistosomiasis is a neglected tropical disease of considerable public health burden. We recently discovered a micromolar activity of several cardenolides against newly transformed schistosomula (NTS) of the parasitic flatworm Schistosoma mansoni in a small compound screen including different substance classes of both natural products as well as synthetic molecules. In further experiments, a focused library of naturally occurring and synthetic steroids was explored against NTS and adult S. mansoni, revealing seven cardenolides with comparable activities as known anthelminthics such as praziquantel. Of these, gomphoside monoacetate and uscharin showed suitable therapeutic indices. In a first in vivo study, at a dose of 10 mg/kg, only minor activity in mice harboring a chronic S. mansoni infection could be shown, which will be further investigated by structure-activity relationship studies as well as pharmacodynamic and pharmacokinetic approaches.


Does Drinking Together Promote Relationship Intimacy? Temporal Effects of Daily Drinking Events.
Although research has documented harms associated with drinking within intimate relationships, there is evidence that some drinking patterns-characterized by congruent or shared partner drinking-may be associated with positive relationship functioning. The present dyadic daily diary study allowed us to consider whether congruent drinking events and drinking with partner increase the likelihood of experiencing intimacy with one's partner within the next few hours. Within a sample of 119 community couples in which both partners drank regularly, we studied the temporal relationship between drinking events and intimacy experiences using 56 days of daily reports. To ensure that the pattern of results was robust, we tested the effects of congruent versus noncongruent drinking events using different characterizations. Drinking episodes involving simultaneous drinking by both partners (but not solo drinking) increased the likelihood of intimacy in the next few hours. Similarly, drinking episodes in which partner was present (but not episodes when partner was absent) and drinking episodes that took place at home (but not away from home) increased the likelihood of intimacy. Results provide the first evidence that some types of drinking events contribute to the occurrence of couple intimacy experiences within the next few hours and help to explain previously observed long-term effects of congruent drinking patterns on couple functioning.


Transcriptome sequencing, annotation and polymorphism detection in the hop bush, Dodonaea viscosa.
The hop bush, Dodonaea viscosa, is a trans-oceanic species distributed oversix continents. It evolved in Australia where it is found over a wide range of habitat types and is an ecologically important species. Limited genomic resources are currently available for this species, thus our understanding of its evolutionary history and ecological adaptation is restricted. Here, we present a comprehensive transcriptome dataset for future genomic studies into this species. We performed Illumina sequencing of cDNA prepared from leaf tissue collected from seven populations of D. viscosa ssp. angustissima and spatulata distributed along an environmental gradient in South Australia. Sequenced reads were assembled to provide a transcriptome resource. Contiguous sequences (contigs) were annotated using BLAST searches against the NCBI non-redundant database and gene ontology definitions were assigned. Single nucleotide polymorphisms were detected for the establishment of a genetic marker set. A comparison between the two subspecies was also carried out. Illumina sequencing returned 268,672,818 sequence reads, which were de novoassembled into 105,125 contigs. Contigs with significant BLAST alignments (E value < 1e(-5))numbered at 44,191, with 38,311 of these having their most significant hits to sequences from land plant species. Gene Ontology terms were assigned to 28,440 contigs and KEGG analysis identified 146 pathways that the gene products from 5,070 contigs are potentially involved in. The subspecies comparison identified 8,494 fixed SNP differences across 3,979 contiguous sequences, indicating a level of genetic differentiation between them. Across all samples, 248,235 SNPs were detected. We have established a significant genomic data resource for D. viscosa,providing a comprehensive transcriptomic reference. Genetic differences among morphologically distinct subspecies were found. A wide range of putative gene regions were identified along with a large set of variable SNP markers, providing a basis for studies into the evolution and ecological adaptation of D. viscosa.


Assembly of Proteins by Free RNA during the Early Phase of Proteostasis Stress.
At any stage of their lifecycle, mRNAs are coated by specialized proteins. One of few circumstances when free mRNA appears in the cytosol is the disassembly of polysomes during the stress-induced shutdown of protein synthesis. Using quantitative mass spectrometry, we sought to identify the free RNA-interacting cellular machinery in heat-shocked mammalian cells. Free RNA-associated proteins displayed higher disorder and larger size, which supports the role of multivalent interactions during the initial phase of the association with RNAs during stress. Structural features of the free RNA interactors defined them as a subset of RNA-binding proteins. The interaction between these assembled proteins in vivo required RNA. Reconstitution of the association process in vitro indicated a multimolecular basis for increased binding to RNA upon heat shock in the cytosol. Our study represents a step toward understanding how free RNA is processed in the cytosol during proteostasis stress.


[Not Available].
A biographical inventory of Italian scientific instrument makers has been conducted through extensive research in public and private collections throughout the world. The time-span is comprised between the 16th and the 18th centuries for each maker information about his signed and dated instruments, categories, collections and references has been given. As the first attempt of a listing of Italian makers, it must be considered as a work in progress. In a short time the text will be transferred on Internet to allow new additions and the corrections brought by the continuation of research.


Asymmetric synthesis of fused bicyclic alpha-amino acids having a hexahydro-cyclopenta[c]pyridine skeleton via intramolecular Pauson-Khand reaction of 1-sulfonimidoyl-substituted 5-azaoct-1-en-7-ynes.
An asymmetric synthesis of fused bicyclic amino acids having a hexahydro-cyclopenta[c]pyridine skeleton and carrying besides an enone structural element a substituent at the beta-position is described. The key steps of the synthesis are a highly selective allylation of N-tert-butylsulfonyl imino ester with bis(allylsulfoximine)titanium complexes and a highly diastereoselective Pauson-Khand cycloaddition of sulfonimidoyl-substituted gamma,delta-unsaturated alpha-amino acid esters carrying a substituent at the beta-position and a propargyl group at the N-atom. The cyclization is accompanied by a reductive cleavage of the sulfoximine group of the primary cyclization product. Surprisingly, the removal of the sulfoximine group proceeds with inversion of the configuration at the S-atom and gives N-methyl-phenylsulfinamide with >/=98% ee. Deprotection of the bicyclic N-tert-butylsulfonyl-protected amino acid ester was accomplished through treatment with CF(3)SO(3)H under anhydrous conditions. The enantio- and diastereomerically pure sulfoximine-substituted gamma,delta-unsaturated alpha-amino acid esters used as starting material were obtained through a highly regio- and diastereoselective allylation of N-tert-butylsulfonyl imino ester with acyclic bis(allylsulfoximine)titanium complexes, described previously.


Molecular pathways in colorectal cancer.
Colorectal cancer (CRC) is the second most common newly diagnosed cancer and accounts for the second highest number of cancer related deaths in Australia, the third worldwide and of increasing importance in Asia. It arises through cumulative effects of inherited genetic predispositions and environmental factors. Genomic instability is an integral part in the transformation of normal colonic or rectal mucosa into carcinoma. Three molecular pathways have been identified: these are the chromosomal instability (CIN), the microsatellite instability (MSI), and the CpG Island Methylator Phenotype (CIMP) pathways. These pathways are not mutually exclusive, with some tumors exhibiting features of multiple pathways. Germline mutations are responsible for hereditary CRC syndromes (accounting for less than 5% of all CRC) while a stepwise accumulation of genetic and epigenetic alterations results in sporadic CRC. This review aims to discuss the genetic basis of hereditary CRC and the different pathways involved in the process of colorectal carcinogenesis.


Poisson-bracket approach to the dynamics of nematic liquid crystals.
We use the general Poisson-bracket formalism for obtaining stochastic dynamical equations for slow macroscopic fields to derive the equations that govern the dynamics of nematic liquid crystals in both their nematic and isotropic phases. For uniaxial molecules, we calculate the Poisson bracket between the tensorial nematic order parameter Q and the momentum density g, as well as those between all pairs of conserved quantities. We show that the full nonlinear hydrodynamical equations for the nematic phase derived in this formalism are identical to the nonlinear Ericksen-Leslie equations. We also obtain the complete dynamical equations for the slow dynamics of the tensorial nematic order parameter Q valid both in the isotropic and the nematic phase. They differ from those obtained by other techniques only in the values of kinetic coefficients and in the number of nonlinear terms in Q, which are present.


Bilateral adrenal metastasis of renal cell carcinoma 4 years after radical nephrectomy: A case report and review of literature.
Renal cell carcinoma (RCC) almost metastasizes to every organ, the possibility of adrenal metastasis is relatively low in patients that have undergone radical nephrectomy, only a few cases of bilateral adrenal metastasis are reported on literature. Although surgical treatment of metastases from RCC is preferred and contributes to the rate of survival, it is considered challenging to manage such cases due to the rarity of bilateral metastasis to the adrenal glands. A 64-year-old Manchus female presented with an incidental ultrasonic finding of a left adrenal mass 4 years after radical nephrectomy for left renal cell carcinoma. Abdominal contrast enhanced CT scan revealed bilateral adrenal masses, suggesting metastatic lesion. Examinations indicated neither local recurrence nor distant metastasis anywhere have been detected by whole body Positron Emission Tomography/Computed Tomography (PET/CT) scan except high radioactive uptake in bilateral adrenal glands. Metachronous bilateral adrenalectomy was taken and laparoscopic right adrenalectomy was first performed. She was discharged home on third postoperative day. Pathological examination revealed metastatic renal cell carcinoma. Two months later she was performed laparoscopic left adrenalectomy. The patient healed without obvious complications and no tumor recurrence. Bilateral metastatic adrenal recurrence from RCC is very rare. Early diagnosis of adrenal metastasis is challenging because they are usually silent both anatomically and functionally. Surgical intervention is a wise option for these patients that may improve survival, and metachronous bilateral adrenalectomy is proved to be safe and effective.


Identification and characterization of a new human cDNA from chromosome 21q22.3 encoding a basic nuclear protein.
Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients. The region proposed to contain the gene(s) for DS CHD has been restricted to 21q22.2-22.3, from D21S55 to MX1. The identification and functional characterization of the genes mapping to this region is a necessary step to understand the pathogenesis of CHD in DS. In an effort to contribute to the construction of a transcriptional map of the DS CHD region we have performed direct cDNA selection using a YAC contig that maps between ETS2 and D21S15 and cDNAs synthesised from fetal heart structures. Here we describe the identification and characterization of a new gene, WRB, that maps to 21q22.3 between ACTL5 and HMG 14 and appears to be widely expressed in adult and fetal tissues. The new gene encodes a basic protein of unknown function containing a tryptophan-rich carboxyl-terminal region and a potential nuclear localization signal. Immunofluorescence analysis shows a predominant localization in the cell nucleus. The understanding of the biological function of the protein product should clarify the potential role of WRB in the pathogenesis of DS CHD.


Anemia in heart failure: to treat or not to treat?
Anemia is a prevalent comorbidity in chronic heart failure (CHF). As studies have demonstrated close links between anemia and a poorer prognosis, there has been an interest in developing treatment strategies for this condition. Anemia is closely associated with disease severity and may be secondary to multiple modifiable causes; therefore, the initial strategies should always include a thorough search for etiology and should focus on optimizing heart failure treatment. Recently, more specific therapies have been assessed, namely erythropoiesis-stimulating agents and iron supplementation therapy. Studies evaluating erythropoietin in heart failure have demonstrated conflicting results to date, with smaller, single-center studies seeming to show a clinical benefit and larger, multicenter trials demonstrating no significant effect on clinical outcome aside from improvement in selected quality-of-life indices. Similarly, studies evaluating iron therapy alone in anemic patients with heart failure have so far shown promising results with regard to clinical and quality-of-life outcomes, but these studies are limited in that they involved small patient numbers. Ongoing studies such as the Reduction of Events With Darbepoetin Alfa in Heart Failure (RED-HF), Iron Supplementation in Heart Failure Patients With Anemia (IRON-HF), and Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trials will determine the value of darbepoetin alfa and intravenous iron replacement therapy in anemic CHF patients.


Modular emergency general surgery training: A pilot study of a novel programme.
Introduction Pan-speciality consensus guidance advocates mandatory emergency general surgery (EGS) training modules for specialist registrars (StRs). This pilot study evaluated the impact of EGS modules aimed at StRs over 1 year. Methods Eleven StRs were allocated a focused 4-week EGS module, in addition to the standard 1:12 on-call duty rota, in a tertiary surgical centre. Primary outcome measures included the number of indicative emergency operations and validated Procedure Based Assessments (PBAs) performed, both during the EGS module and over the training year. Results StRs performed a median of 11 (range 5-15) laparotomies during the EGS module versus 31 (range 9-49) over the whole training year. StRs attended 43.7% of available laparotomies during the module (range 24.1-63.7%). EGS modules provided more than one-third of the total emergency laparotomy experience, and a quarter of the emergency colectomy, appendicectomy and Hartmann's procedure experience. There were no differences in EGS module-related outcomes between junior and senior StRs. Significantly more PBAs related to laparotomy and segmental colectomy were completed during EGS modules than the on-call duty rota, at 32% versus 14% (p<0.001) and 48% versus 22% (p=0.019), respectively. Performance levels were maintained following module completion. Conclusions These findings provide an important baseline when considering future modular EGS training.


An electronic patient-reported outcome created based on my needs is worth using: an explorative qualitative study investigating young people's opinions for a health assessment tool.
Young people in different healthcare settings are positive about using electronic patient-reported outcomes (ePROs), which are meant to increase the effectiveness and safety of interventions from the patient's perspective. Sweden offers free healthcare to young people aged 12-25 years at 275 youth health clinics (YHCs), whose goals are to strengthen young people and promote sexual, physical, and mental health. YHCs need effective ways to identify the overall picture of young people's health and health-related problems. To our knowledge, there is no ePRO for YHCs that provides an overview of young people's health from several health perspectives. The aim of this study was to explore young people's view on content and design of an ePRO to provide an overview of their health and health related problems when visiting a YHC, and their opinion on what healthcare needs to consider when using the ePRO. This was an explorative qualitative study. The participants were included from five YHCs, in different socioeconomic areas in central Sweden. Fifteen participants were included: 10 girls, three boys, and two non-binary participants with an age range of 16-22 years. Data were collected using a semi-structured interview guide and individual interviews, and inductive content analysis was performed. One main theme, "ePRO created based on my needs is worth using" and two sub-themes, "Appealing content and design" and "Trusting healthcare", emerged. The participants wanted that an ePRO should include overall questions about mental-, physical-, and sexual health and social support. Participants also believed the ePRO must disclose the risks of self-harm or suicide. The participants noted the importance of emotional and digital security when using the ePRO and having a confidential conversation with a healthcare provider. To share health information means to trust to gain health. The study participants' views on content and design can form the basis for designing an ePRO for young people. Their thoughts on safety and treatment in healthcare can be considered in the development process. This study is the starting point for developing an ePRO for young people at YHCs.


Adapting the short form of the Coping Inventory for Stressful Situations into Chinese.
The Coping Inventory for Stressful Situations (CISS) is a measurement tool for evaluating stress that has good psychometric properties. We investigated the applicability of a short-form version of the CISS in a large sample of Chinese university students. Nine hundred and seventy-two Chinese university students aged 18-30 years (mean =20.15, standard deviation =3.26) were chosen as subjects, of whom 101 were randomly selected to be retested after a 2-week interval. The results of a confirmatory factor analysis revealed that the root mean square error of approximation of a four-factor model was 0.06, while the comparative fit index was 0.91, the incremental fit index was 0.93, the non-normed fit index was 0.91, and the root mean residual was 0.07. The Cronbach's α coefficients for the task-oriented, emotion-oriented, distraction, and social diversion coping subscales were 0.81, 0.74, 0.7, and 0.66, respectively. The 2-week test-retest reliability was 0.78, 0.74, 0.7, and 0.65 for the task-oriented, emotion-oriented, distraction, and social diversion coping subscales, respectively. In the Chinese version of the CISS short form, task-oriented coping was positively correlated with positive affect and extraversion and negatively correlated with neuroticism; emotion-oriented coping was negatively correlated with extraversion and positively correlated with negative affect, anxiety, and neuroticism; distraction coping was positively correlated with neuroticism, extroversion, anxiety, positive affect, and negative affect and negatively correlated with psychoticism; and social diversion coping was positively correlated with extroversion and positive affect and negatively correlated with psychoticism. The Chinese version of the CISS short form is satisfactorily valid and reliable among Chinese university students.


Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core.
Hepatitis C virus genotype-3a (HCV-3a) is directly linked to steatosis development. We studied the effects of HCV-3a core protein on the promoter activity of fatty acid synthase (FAS), a major enzyme involved in de novo lipid synthesis. HCV-3a and -1b core genes were cloned and expressed. Using a FAS promoter-luciferase reporter, we demonstrated that both HCV-3a and -1b core proteins up-regulated the FAS promoter. However, HCV-3a core protein expression induced significantly higher FAS promoter activity than HCV-1b core. We further showed that FAS up-regulation by HCV core was dependent on transcription factor sterol response element binding protein-1. Mutational analysis showed that processing of HCV core protein of different genotypes was differentially involved in FAS promoter up-regulation. Although lipid droplet localization of HCV core protein was not important for FAS up-regulation, a specific amino acid residue (Phe(164)) within the FATG lipid droplet localization sequence of HCV-3a core protein played a major role in the stronger FAS activation by HCV-3a core. The stronger effect of HCV-3a core protein on FAS activation in comparison to HCV-1b core could contribute to the higher prevalence and severity of steatosis in HCV-3a infections.


[Possibilities of neural therapy in internal medicine].
Neural therapy is the diagnostic-therapeutic application of local anaesthetics, in order to be able to treat functional, painful, reversible diseases, disturbed regulations including inflammations. The results of the cure are to be explained by complex neurophysiologic, electrophysiologic, molecularbiologic, immunologic, humoral and thus cybernetic courses of reaction. Neural therapy is to be used under two complexes. Firstly, symptomatically in the segment as weal, in trigger points, on and in joint structures, in vessels, muscular and tendon attachments, sympathetic-parasympathetic ganglia in order to cause a regulating effect, for instance by interruption of nociceptive afferences, blocking of sympathetic efferent reflexes in the sense of the sympathetic reflex dystrophy. Secondly, causally at the focus of disturbance or in the peripheral irritation centre, which may be a scar, the nasopharyngeal space, the abdomen, the spine and other things, in order to eliminate the cause of the disturbance. From the variety of the effects of the local anaesthetics, like membrane stabilizing, antihistaminic, catecholamine-decreasing, choline receptor inhibiting, antiarrhythmic at the cardiac muscle results their multifarious use, also in internal medicine. The neural therapy is effective, economic, poor in side effects, closes therapeutic gaps and is well to be combined with other successful medical treatments, especially of reflex-therapeutic kind. Exact clinical diagnostics, good knowledge in anatomy, technical ability of the therapeutist as well as theoretical basic knowledge are prerequisite for the use of the neural therapy.


Ankle fractures in diabetic neuropathic arthropathy: can tibiotalar arthrodesis salvage the limb?
Between 2000 and 2006 we performed salvage tibiotalar arthrodesis in 17 diabetic patients (17 ankles) with grossly unstable ankles caused by bimalleolar fractures complicated by Charcot neuro-arthropathy. There were ten women and seven men with a mean age of 61.6 years (57 to 69). A crossed-screw technique was used. Two screws were used in eight patients and three screws in nine. Additional graft from the malleoli was used in all patients. The mean follow-up was 26 months (12 to 48) and the mean time to union was 5.8 months (4 to 8). A stable ankle was achieved in 14 patients (82.4%), nine of whom had bony fusion and five had a stiff fibrous union. The results were significantly better in underweight patients, in those in whom surgery had been performed three to six months after the onset of acute Charcot arthropathy, in those who had received anti-resorptive medication during the acute stage, in those without extensive peripheral neuropathy, and in those with adequate peripheral oxygen saturation (> 95%). The arthrodesis failed because of avascular necrosis of the talus in only three patients (17.6%), who developed grossly unstable, ulcerated hindfeet, and required below-knee amputation.


Aberrations of spherocylindrical spectacle lenses.
A procedure has been developed for tracing a bundle of rays through and ophthalmic lens and a schematic eye with its primary line of sight pointed through various parts of the lens. A bundle of eight rays can provide data for assessing the quality of the image formed by such a system. To test the procedure and to generate data which can help in selecting a method for evaluating image quality, we selected a single lens as an example. The lens selected has a spherical back surface (-5.00 diopters) and a toric front surface (+15.00 diopters in the vertical and /10.00 diopters in the horizontal). It has a center thickness of 5 mm and glass of index 1.523. Spot diagrams were generated with the eye pointed in various directions through the ophthalmic lens. The data generated showed that peripheral bundles which fall between the principal meridians emerge as astigmatic bundles. This leads to the proposal that blur circle theory can be used for evaluating the quality of the optical image and that it suffices in the case of a spherocylindrical ophthalmic lens to base the tolerances for refractive power on measurements made in the principal meridians.


Global health education in U.S. medical schools.
Interest in global health (GH) among medical students worldwide is measurably increasing. There is a concomitant emphasis on emphasizing globally-relevant health professions education. Through a structured literature review, expert consensus recommendations, and contact with relevant professional organizations, we review the existing state of GH education in US medical schools for which data were available. Several recommendations from professional societies have been developed, along with a renewed emphasis on competencies in global health. The implementation of these recommendations was not observed as being uniform across medical schools, with variation noted in the presence of global health curricula. Recommendations for including GH in medical education are suggested, as well as ways to formalize GH curricula, while providing flexibility for innovation and adaptation.


Development of Vibrational Frequency Maps for Nucleobases.
Vibrational spectroscopy provides a powerful tool to probe the structure and dynamics of nucleic acids because specific normal modes, particularly the base carbonyl stretch modes, are highly sensitive to the hydrogen bonding patterns and stacking configurations in these biomolecules. In this work, we develop vibrational frequency maps for the C═O and C═C stretches in nucleobases that allow the calculations of their site frequencies directly from molecular dynamics simulations. We assess the frequency maps by applying them to nucleobase derivatives in aqueous solutions and nucleosides in organic solvents and demonstrate that the predicted infrared spectra are in good agreement with experimental measurements. The frequency maps can be readily used to model the linear and nonlinear vibrational spectroscopy of nucleic acids and elucidate the molecular origin of the experimentally observed spectral features.


The obstetric patient in the Covid pandemic: anaesthesia and perioperative care.
: The Coronavirus Disease 2019 (COVID-19) pandemic has had an unprecedented impact on pregnant women, maternity services and healthcare workers. We review recent literature on the course of COVID-19 infection in pregnancy, and recommendations for treatment and service provision. It has been increasingly recognised that pregnant women are at higher risk of severe disease associated with COVID-19 infection. Early critical care input is crucial to guide respiratory support and techniques such as prone positioning, with a low threshold for intubation in critical illness. Timing of delivery remains a highly individualised decision. Following the RECOVERY trial, the use of a course of steroids in cases of severe COVID-19 infection has been widely adopted, and emerging guidance recommends vaccination in pregnant women. Rapidly emerging evidence has helped guide clinicians to identify those patients most at risk of severe disease in COVID-19 and implement early interventions to reduce morbidity and mortality.


The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters.
This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (n = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:1 omega-7), a low proportion of linoleic acid (18:2 omega-6), and a relatively high content of gamma-linolenic (18:3 omega-6) and dihomo-gamma-linolenic (20:3 omega-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-gamma-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.


Difference of neuromuscular responses by additional loads during plyometric jump.
Plyometric training is a training method to increase the motor output, stretch-shortening cycle which could be associated with power output. To increase the neuromuscular output, various training variables have been incorporated in training programs. Weight vest is one of the variables to develop it. However, how much load can effectively develop the neural response is still not clearly understood. The aim of this study was to identify the effects of additional external loads on neuromuscular response of lower body during plyometric jump. Total 19 men performed jump tests with weight vest (two jumps in each additional load; 0%, 10%, 15% and 20% of bodyweight [BW]). During the tests, neuromuscular responses of lower extremity were measured. In vertical jump, 0%BW group was higher than the other heavier loads. In rate of force development (RFD), 10%BW was higher than 15%BW and 20%BW. In 0-30 msec of interval RFD, the heavier load groups were greater than 0%BW and in 0-50 msec, 15%BW and 20%BW were higher than 0%BW. In neuromuscular efficiency (NME), 15%BW and 20%BW were greater than 0%BW in ankle joint. This research indicated that plyometric jump with additional load causes greater RFD and NME of lower extremity compared with jump training without additional load. During weight vest plyometric jump, 10%-20% of BW load is advantageous to NME of lower body and 10% of BW load is effective to develop RFD of lower extremity.


LIFE-HISTORY VARIATION AND COMPARATIVE PHYLOGEOGRAPHY OF DARTERS (PISCES: PERCIDAE) FROM THE NORTH AMERICAN CENTRAL HIGHLANDS.
Phylogeography seeks to evaluate the relationship between genetic variation and geographic distribution of a species to examine the influence of historical events on divergence. Congruent phylogeographic patterns in codistributed species indicate historical association of the taxa being compared, and the uniform action of biogeographic events in shaping genetic variation. We sought to evaluate the congruence of patterns of genetic variation of five closely related fish species across a well-defined biogeographic boundary. We gathered allozymic and mitochondrial DNA (mtDNA) sequence data for five species of darters (Percidae: Etheostomatini) from populations distributed among biogeographic regions in the Ozark and Ouachita highlands of the south-central United States. Comparisons among species revealed noncongruence in the magnitude of genetic divergence in both allozymes and mtDNA sequences. We hypothesized that noncongruence resulted, in part, from differences in life histories of the species in our comparison. To address this hypothesis, we evaluated the association between gene flow (measured by Ne m) and variation in body size and fecundity variables because they have been shown to influence gene flow in fishes. Correlation analysis revealed an association between gene flow and fecundity (r = 0.88), but not with body size (r = 0.36) or reproductive investment per individual (r = -0.23). The result was similar when independent contrasts of the original variables were used in correlation analyses. Phylogeographic analysis of mtDNA sequence data indicated the importance of history, evident in gene trees of Percina nasuta and Percina phoxocephala. Divergence rates between these two taxa may differ because of historically persistent differences in population sizes, reflected in present-day abundance and fecundity differences. Conversely, Percina caprodes showed little evidence of divergence in mtDNA sequences and yielded the highest mean Ne m values from allozyme data. Comparisons among closely related, codistributed taxa may help discriminate among the possibilities for noncongruence in biogeographic studies by allowing evaluation of the influence of life history on patterns of gene flow.


ProteomeCommons.org collaborative annotation and project management resource integrated with the Tranche repository.
ProteomeCommons.org has implemented a resource that incorporates concepts of Web 2.0 social networking for collaborative annotation of data sets placed in the Tranche repository. The annotation tools are part of a project management resource that is effective for individual laboratories or large distributed groups. The creation of the resource was motivated by the need for a way to encourage annotation of data sets with high accuracy and compliance rates. The system is designed to respond to the dynamic nature of research in an easy-to-use fashion through the use of a dynamic data model that does not inhibit the innovation that is important for basic research. Placing the annotation tool within a project manager allows annotation to occur over the life of the project and provides the security and monitoring capabilities needed for large or small collaborative projects. The resource effectively supports distributed groups of investigators working on common data sets and is available immediately at https://ProteomeCommons.org . In addition, a silver compliant data resource based on ProteomeCommons.org has been developed for cancer Biomedical Informatics Grid (caBIG) to allow much broader access to the annotations describing data sets in the Tranche repository.


Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction.
Subfertility is a condition found in up to 15% of couples of reproductive age. Gamete micromanipulation, such as intracytoplasmic sperm injection (ICSI), is very useful for treating couples with compromised sperm parameters. Recently a new method of sperm selection named 'motile sperm organelle morphology examination' (MSOME) has been described and the spermatozoa selected under high magnification (over 6000x) used for ICSI. This new technique, named intracytoplasmic morphologically selected sperm injection (IMSI), has a theoretical potential to improve reproductive outcomes among couples undergoing assisted reproduction techniques (ART). To compare the effectiveness and safety of IMSI and ICSI in couples undergoing ART. We searched for randomised controlled trials (RCT) in electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); in addition, we handsearched the reference lists of included studies and similar reviews. We performed the last electronic search on 8 May 2013. We considered only truly randomised controlled trials comparing ICSI and IMSI to be eligible; we did not include quasi or pseudo-randomised trials. We included studies that permitted the inclusion of the same participant more than once (cross-over or 'per cycle' trials) only if data regarding the first treatment of each participant were available. Two review authors independently performed study selection, data extraction, and assessment of the risk of bias and we solved disagreements by consulting a third review author. We corresponded with study investigators in order to resolve any queries, as required. The search retrieved 294 records; from those, nine parallel design studies were included, comprising 2014 couples (IMSI = 1002; ICSI = 1012). Live birth was evaluated by only one trial and there was no significant evidence of a difference between IMSI and ICSI (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.79 to 1.64, 1 RCT, 168 women, I(2) = not applicable, low-quality evidence). IMSI was associated with a significant improvement in clinical pregnancy rate (RR 1.29, 95% CI 1.07 to 1.56, 9 RCTs, 2014 women, I(2) = 57%, very-low-quality evidence). We downgraded the quality of this evidence because of imprecision, inconsistency, and strong indication of publication bias. We found no significant difference in miscarriage rate between IMSI and ICSI (RR 0.82, 95% CI 0.59 to 1.14, 6 RCTs, 552 clinical pregnancies, I(2) = 17%, very-low-quality evidence). None of the included studies reported congenital abnormalities. Results from RCTs do not support the clinical use of IMSI. There is no evidence of effect on live birth or miscarriage and the evidence that IMSI improves clinical pregnancy is of very low quality. There is no indication that IMSI increases congenital abnormalities. Further trials are necessary to improve the evidence quality before recommending IMSI in clinical practice.


Triage for health care in a metropolis: Paris under Napoleon.
Paris under Napoleon offers the earliest example of medical patient triage in a metropolis. A central admitting office opened at the Hotel-Dieu of Paris in 1801 under the supervision of a municipal hospital council. It admitted about 22,000 patients in the first eighteen months. This number represented about 44% of all applicants; another 16,000 were admitted to various hospitals as emergencies; the rest were treated as outpatients and helped on the spot or referred to district welfare offices, dispensaries, and nursing homes. Thus the historian can discern a concerted effort by hospital authorities to keep indigent patients out of the hospital.


Quantitative evaluation of protein-protein and ligand-protein equilibria of a large allosteric enzyme by electrospray ionization time-of-flight mass spectrometry.
A mass spectrometer coupling electrospray ionization with time-of-flight mass spectrometry (ESI-TOFMS) has been used to investigate the oligomeric species of Escherichia coli citrate synthase, and to determine the effect of nicotinamide adenine dinucleotide (NADH), an allosteric inhibitor of this enzyme, on the equilibrium between the oligomeric forms. An equilibrium mixture of dimers (M = 95,770 Da) and hexamers (M = 287,310 Da) was found under the conditions used (KA = 6.9 x 10(10) M-2), and NADH was observed to bind selectively to the hexamer (KD = 1.1 microM), shifting the equilibrium to the latter form. The power of ESI-TOFMS to measure ions of very large mass-to-charge ratio (up to m/z approximately 10,000 in this case) is shown to be a valuable tool for obtaining accurate information about compositions of noncovalent complexes and equilibrium constants. The measured constants agree with those determined by conventional means.


Qualitative and quantitative evaluation of chrysotile and crocidolite fibers with IR-spectroscopy: application to asbestos-cement products.
Infrared (IR) spectrophotometry allows simple and quick qualitative and quantitative evaluations of different kinds of asbestos, as well as of other inorganic particles. In particular, chrysotile and crocidolite have characteristic IR spectra and optical density measures of 2,710 nm band for chrysotile, of 12,820 nm band for crocidolite permit quantitative evaluation of each fiber alone or in mixture. IR spectra also give informations about changes of fiber structure and of chemical composition due, for example, to thermal treatment or acid leaching. The analytical method we developed can detect levels as low as 0.1 mg of fiber in a 300 mg disk of KBr using a low cost IR spectrophotometer. The use of a Fourier Transform IR spectrophotometer (FTIR) improves dramatically the sensitivity and selectivity. Computer assisted analysis of spectra offers the possibility to reduce matrix interferences and to compare different spectra. Examples of IR technique applied to asbestos-cement products and insulating materials are presented.


The positive effect of plant diversity on soil carbon depends on climate.
Little is currently known about how climate modulates the relationship between plant diversity and soil organic carbon and the mechanisms involved. Yet, this knowledge is of crucial importance in times of climate change and biodiversity loss. Here, we show that plant diversity is positively correlated with soil carbon content and soil carbon-to-nitrogen ratio across 84 grasslands on six continents that span wide climate gradients. The relationships between plant diversity and soil carbon as well as plant diversity and soil organic matter quality (carbon-to-nitrogen ratio) are particularly strong in warm and arid climates. While plant biomass is positively correlated with soil carbon, plant biomass is not significantly correlated with plant diversity. Our results indicate that plant diversity influences soil carbon storage not via the quantity of organic matter (plant biomass) inputs to soil, but through the quality of organic matter. The study implies that ecosystem management that restores plant diversity likely enhances soil carbon sequestration, particularly in warm and arid climates.


The effect of controlled oral hygiene in overdenture wearers.
The effect of controlled oral hygiene was studied in 40 patients treated with immediate complete overdentures in one or both jaws. Before prosthetic treatment conservative periodontal treatment was conducted with intensive instruction and motivation in oral hygiene care. Caries and periodontal status were recorded before and 2-4 weeks (day 0), 6 months, and 12 months after prosthetic treatment. However, the patients were seen more frequently for motivation and professional tooth cleaning. The material included 44 overdentures with a total of 92 abutments, with 1-4 abutments in each jaw. Before treatment the overall mean plaque index score was 1.43 +/- 0.68 and the overall mean gingival index score 1.57 +/- 0.53, and on day 0 and after 6 and 12 months the overall mean PlI score was 0.33-0.65 and the overall mean GI score 0.67-0.97. Adjacent to the abutments there was a significant reduction of the PlI and the GI scores from before treatment to day 0 and from day 0 to 6 months after prosthetic treatment (P less than 0.001). There was a significant reduction of pocket depth from day 0 to 6 months and from 6 to 12 months (P less than 0.01). The results of this study have shown that it is possible to maintain teeth as abutments for overdentures in patients with an initial poor dental status.


Intracerebral Administration of a Novel Self-Assembling Peptide Hydrogel Is Safe and Supports Cell Proliferation in Experimental Intracerebral Haemorrhage.
Intracerebral haemorrhage (ICH) is the deadliest form of stroke, but current treatment options are limited, meaning ICH survivors are often left with life-changing disabilities. The significant unmet clinical need and socioeconomic burden of ICH mean novel regenerative medicine approaches are gaining interest. To facilitate the regeneration of the ICH lesion, injectable biomimetic hydrogels are proposed as both scaffolds for endogenous repair and delivery platforms for pro-regenerative therapies. In this paper, the objective was to explore whether injection of a novel self-assembling peptide hydrogel (SAPH) Alpha2 was feasible, safe and could stimulate brain tissue regeneration, in a collagenase-induced ICH model in rats. Alpha2 was administered intracerebrally at 7 days post ICH and functional outcome measures, histological markers of damage and repair and RNA-sequencing were investigated for up to 8 weeks. The hydrogel Alpha2 was safe, well-tolerated and was retained in the lesion for several weeks, where it allowed infiltration of host cells. The hydrogel had a largely neutral effect on functional outcomes and expression of angiogenic and neurogenic markers but led to increased numbers of proliferating cells. RNAseq and pathway analysis showed that ICH altered genes related to inflammatory and phagocytic pathways, and these changes were also observed after administration of hydrogel. Overall, the results show that the novel hydrogel was safe when injected intracerebrally and had no negative effects on functional outcomes but increased cell proliferation. To elicit a regenerative effect, future studies could use a functionalised hydrogel or combine it with an adjunct therapy.


Absorption, distribution, metabolism, and excretion of 2,2-bis(bromomethyl)-1,3-propanediol in male fischer-344 rats.
2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant, previously shown to be a multisite carcinogen in experimental animals. Studies were performed to characterize the dispositional and metabolic fate of BMP after oral or intravenous administration to male Fischer-344 rats. After a single oral administration of [(14)C]BMP (10 or 100 mg/kg) >80% of the low dose and 48% of the high dose were excreted by 12 h in the urine predominantly as a glucuronide metabolite. After repeated daily oral doses for 5 or 10 days, route and rate of elimination were similar to those obtained after single administrations of BMP. In all studies, the radioactivity recovered in feces was low (<15%). The total amount of radioactivity remaining in tissues at 72 h after a single oral administration of BMP (100 mg/kg) was less than 1% of the dose, and repeated daily dosing did not lead to retention in tissues. After intravenous administration, the radiolabel found in blood decreased rapidly. Excretion profiles were similar to those after oral administration. Parent BMP and BMP glucuronide were present in blood plasma after oral or intravenous dosing. After an intravenous dose of BMP (15 mg/kg) the hepatic BMP glucuronide was primarily exported into the bile (>50% within 6 h), but it underwent enterohepatic recycling with subsequent elimination in the urine. These data indicate that the extensive extraction and rapid glucuronidation by the liver limits exposure of internal tissues to BMP by greatly reducing its systemic bioavailability after oral exposure.


The prevalence of hepatitis B virus infection in Nigerian children prior to vaccine introduction into the National Programme on Immunization schedule.
Hepatitis B virus infection is a major global health problem of public health importance. In a bid to control the infection, the Nigerian government in 2004 introduced hepatitis B vaccine into the National Program on Immunization. There are no studies on the prevalence of hepatitis B in adolescent prior to 2004. The study was aimed at determining the seroprevalence and predictors of viral Hepatitis B in Nigerian children aged 11-19 years. A cross sectional analytical study was conducted in July 2014. Multi-staged sampling technique was used to select 749 children from six secondary schools in Calabar, Cross River State, Nigeria. Ethical clearance was obtained from the Cross River State Medical Ethical Committee. A validated structured interviewer administered questionnaire was used to obtain information from participants following parental consent. Blood samples were obtained for qualitative detection of HBsAg using rapid chromatographic immunoassays with test kits from ABON (China) having sensitivity, specificity and accuracy of >99%, 97% and 98.5% respectively. Data was analyzed using SPSS version 20.2. Nine of the749 students screened were positive for HBsAg giving an overall prevalence of 1.2%. The sex specific prevalence was 0.8% for males and 1.8% for females. After multivariate analysis, age was the predictor of hepatitis B infection (OR 3.92; 95% CI 1.22-12.63; p-value 0.02). The prevalence of HBV infection was low. Despite the low prevalence, the introduction of the vaccine is justifiable in view of the public health importance of the infection.


What do physicians gain (and lose) with experience? Qualitative results from a cross-national study of diabetes.
An empirical puzzle has emerged over the last several decades of research on variation in clinical decision making involving mixed effects of physician experience. There is some evidence that physicians with greater experience may provide poorer quality care than their less experienced counterparts, as captured by various quality assurance measures. Physician experience is traditionally narrowly defined as years in practice or age, and there is a need for investigation into precisely what happens to physicians as they gain experience, including the reasoning and clinical skills acquired over time and the ways in which physicians consciously implement those skills into their work. In this study, we are concerned with 1) how physicians conceptualize and describe the meaning of their clinical experience, and 2) how they use their experience in clinical practice. To address these questions, we analyzed qualitative data drawn from in-depth interviews with physicians from the United States, United Kingdom, and Germany as a part of a larger factorial experiment of medical decision making for diabetes. Our results show that common measures of physician experience do not fully capture the skills physicians acquire over time or how they implement those skills in their clinical work. We found that what physicians actually gain over time is complex social, behavioral and intuitive wisdom as well as the ability to compare the present day patient against similar past patients. These active cognitive reasoning processes are essential components of a forward-looking research agenda in the area of physician experience and decision making. Guideline-based outcome measures, accompanied by underdeveloped age- and years-based definitions of experience, may prematurely conclude that more experienced physicians are providing deficient care while overlooking the ways in which they are providing more and better care than their less experienced counterparts.


Cortical neuroplasticity in patients recovering from acute optic neuritis.
Patients with optic neuritis (ON) undergo cortical and subcortical neuroplasticity as revealed by functional magnetic resonance imaging (fMRI). However, the effect of the heterogeneity of scotomas has not been adequately addressed previously. We introduce a new method of modelling scotomas in fMRI, to reveal a clearer pattern of neuroplasticity, across a mixed patient population. A longitudinal fMRI-study of visual function in 19 ON patients examined at four timepoints between presentation and 6 months was performed. Four different models were compared. The first model included the four different examination timepoints as separate explanatory variables without adjustment for visual field defects. The second model also included covariates reflecting subject-specific deviations in visual field defect from the average group value of the Humphrey mean deviation (HMD) at each examination timepoint. In the third and fourth models the four examination timepoints were not modelled explicitly, but entered vicariously through the associated changes in the HMD for each subject that marked their individual recovery. The results show that the third and fourth models were more sensitive to geniculate and visual cortical neuroplasticity during recovery. Moreover, inferences from the fourth model can be extended to the general population of patients recovering from ON. In conclusion, we present a method of accommodating subject-specific differences between patients with acute ON by inclusion of an HMD-index. This method is sensitive to the processes of neuroplasticity whilst the generalisation of inferences makes the method suitable for future studies of treatment.