[Preiser's disease: a five-case series].
Preiser's disease, or avascular necrosis of the scaphoid occurs without fracture or non-union. Between 1998 and 2009, the authors report on 5 patients who complained of mild pain on the radial aspect of the wrist, associated with stiffness and/or loss of strength. Our management consisted in different options: one bilateral intraarticular injection of hyaluronic acid, three vascularised radial bone graft and one resection of the first carpal row. With four and a half years follow-up, our results are quite satisfactory for improvement of pain, sometimes with residual postoperative stiffness. Management remains difficult because Preiser's disease is rare and there are no relevant prospective control studies. We attempt to provide an algorithm for early management of the disease and to answer the question: "until when can we save the scaphoid and how?"


Genetic diversity of Haemophilus parasuis from sick and healthy pigs.
A collection of 94 Haemophilus parasuis isolates was used for this study. It consisted of isolates from organs of pigs with Glässer's disease and pneumonia (n=54), from nasal swabs of healthy pigs in farms without Glässer's disease problems (n=25), and 15 reference strains. These isolates were typed using a new multilocus variable number of tandem repeats analysis (MLVA) protocol and investigated for the presence of nine putative virulence genes. The new MLVA protocol was highly discriminatory (54 types identified and discrimination index of 97.4%) and reproducible. Similar to previous investigations done with other methods, two major genetic clusters were identified by MLVA, which partially correlated with serotype and virulence gene distributions. Gene linkage analysis suggested that lateral gene transfer occurs within each of these clusters, but rarely between them. Although one single MLVA type included more than 20% of the clinical isolates, no significant correlation was detected between a specific MLVA type, the major genetic clusters, or the presence of any of the virulence genes investigated or the source of the isolates (clinical infection vs. healthy pig). The MLVA typing protocol described in this study is a promising new tool for future investigations into the epidemiology of Glässer's disease and could help us to better understand interacting microbial, host and environmental factors that lead to the development of H. parasuis disease.


Shared allergenic and antigenic determinants in Alternaria and Stemphylium extracts.
Alternaria and Stemphylium extracts were compared by means of various immunochemical and biologic methods. Skin-test responses to Alternaria and Stemphylium in allergic patients were positively correlated, and RAST binding values with the sera of 30 patients utilizing solid-phase Alt-I, Alternaria (70% ammonium sulfate--precipitable fraction), and Stemphylium allergens showed significant correlation, giving evidence for the presence of common allergenic determinants among these three extracts. In RAST inhibition assays, Alternaria and Stemphylium extracts exhibited dose-related inhibiton with solid-phase Stemphylium, Alternaria, and Alt-I, confirming the presence of Alt-I as the major shared allergenic fraction in the two extracts. In repetitive absorption experiments, both Alt-I and Alternaria solid-phase allergens absorbed Stemphylium-specific IgE antibodies from a 12-person serum pool. Similarly, Stemphylium solid-phase allergen absorbed both Alternaria- and Alt-I--specific IgE antibodies. Double-antibody radioimmunoassay for Alt-I showed higher Alt-I activity in Stemphylium than in Alternaria extract. In double-immunodiffusion experiments with rabbit anti--Alt-I antibodies, both Stemphylium and Alternaria extracts produced precipitin lines of identity with Alt-I. The antigenic relationship of the two crude extracts was further confirmed by crossed and crossed-line immunoelectrophoresis experiments. Our results showed that Alternaria and Stemphylium extracts contain multiple shared allergenic and antigenic determinants, including Alt-I.


Investigating Electrode Flooding in a Flowing Electrolyte, Gas-Fed Carbon Dioxide Electrolyzer.
Managing the gas-liquid interface within gas-diffusion electrodes (GDEs) is key to maintaining high product selectivities in carbon dioxide electroreduction. By screening silver-catalyzed GDEs over a range of applied current densities, an inverse correlation was observed between carbon monoxide selectivity and the electrochemical double-layer capacitance, a proxy for wetted electrode area. Plotting current-dependent performance as a function of cumulative charge led to data collapse onto a single sigmoidal curve indicating that the passage of faradaic current accelerates flooding. It was hypothesized that high cathode alkalinity, driven by both initial electrolyte conditions and cathode half-reactions, promotes carbonate formation and precipitation which, in turn, facilitates electrolyte permeation. This mechanism was reinforced by the observations that post-test GDEs retain less hydrophobicity than pristine materials and that water-rinsing and drying electrodes temporarily recovers peak selectivity. This knowledge offers an opportunity to design electrodes with greater carbonation tolerance to improve device longevity.


Effects of Dietary Approaches to Stop Hypertension (DASH)-style diet on fatal or nonfatal cardiovascular diseases--incidence: a systematic review and meta-analysis on observational prospective studies.
Cardiovascular diseases (CVDs) are a group of disorders affecting heart and blood vessels. However, protective roles are proposed for Dietary Approaches to Stop Hypertension (DASH)-style diets. The aim of this review was to summarize and if possible quantify the longitudinal effects of a DASH-style diet on the incidence of CVDs. Pubmed, ISI web of science, and EMBASE were searched and cohort studies that examined the DASH-style diet in relation to CVDs, coronary heart disease (CHD), stroke, and heart failure (HF) were selected. Cohort studies which included participants with specific CVD risk factors like diabetes mellitus, metabolic syndrome, obesity or hypertension were excluded from review. Relative risks (RRs) that were reported for fully adjusted models and their confidence intervals were extracted for meta-analysis. Regarding the adherence to the DASH diet and the incidence of CVDs, stroke, CHD, and HF, only 6 studies met our criteria to be included in this systematic review. Meta-analysis showed that imitating a DASH-like diet can significantly reduce CVDs (RR = 0.80; 95% confidence interval [CI], 0.74-0.86; P < 0.001), CHD (RR = 0.79; 95% CI, 0.71-0.88; P < 0.001), stroke (RR = 0.81, 95% CI, 0.72-0.92; P < 0.001), and HF (RR= 0.71, 95% CI, 0.58-0.88; P < 0.001) risk. A linear and negative association was obtained between DASH-style diet concordance and all CVDs, as well. In conclusion, our results showed that a DASH-like diet can significantly protect against CVDs, CHD, stroke, and HF risk by 20%, 21%, 19% and 29%, respectively. Furthermore, there is a significant reverse linear association between DASH diet consumption and CVDs, CHD, stroke, and HF risk.


Two-year results of laser treatment for retinopathy of prematurity at a single neonatal intensive care unit.
To present the 2-year results of all patients receiving laser treatment for retinopathy of prematurity (ROP) at a single institution over a 9.5-year period. To establish the frequency of threshold ROP. Consecutive case series. All patients who had laser treatment for ROP at The Royal Women's Hospital, Melbourne, Australia, between January 1992 and July 2001 were prospectively recorded in a database. Their medical charts were retrospectively reviewed. Baseline birthweight, gestational age at birth, timing of treatment, and ROP severity at treatment were recorded. The main outcome measures were visual acuity (significantly reduced or not), anatomic outcome and refractive error at 2 years of age (corrected for the degree of prematurity). A total of 107 eyes of 57 babies were treated with laser photocoagulation. Four children did not survive for follow-up, and 2-year follow-up data were available for 38 children (67%, 71 treated eyes). Average duration of follow-up was 26 months. Two-year visual acuity was significantly reduced in 12/71 (17%) treated eyes, and 3/38 children (8%) had significantly reduced vision in both eyes. An anatomical outcome of macular fold or worse was observed in 8/71 eyes (11%). Mean 2-year spherical equivalent refractive outcome was only minimally myopic (-0.6 D). Visual, anatomic and refractive outcomes after laser treatment for ROP were favourable, confirming that laser photocoagulation is an effective treatment for severe ROP.


Sol-gel monolithic anion-exchange column for capillary electrochromatography.
A single-step approach has been used to prepare a monolithic electrochromatographic column by sol-gel processing of an organofunctional silicon alkoxide precursor that contains a propyl-N,N,N-trimethylammonium group. We have found that the time of adding the porogen, poly(ethylene glycol), during the sol-gel reaction affected the separation performance. Since the surface charge of this material is switchable in sign upon manipulation of solution pH, the direction and magnitude of the electroosmotic flow (EOF) can be controlled by adjusting the pH of the running electrolyte. By controlling the direction of the EOF from cathode to anode, inorganic anions can be separated in a short time. Because of the quaternary ammonium functional group, the resulting material is anion exchangeable. Interestingly, the anion-exchange selectivity of inorganic anions on this column changes with solution pH or applied voltage. The column shows excellent run to run reproducibility (R.S.D.<0.4%), good day to day reproducibility (R.S.D.<4%), and reasonable column to column reproducibility (R.S.D.<9%).


Increased sensitivity and specificity of a sandwich ELISA for measurement of IgE antibodies.
We have developed a sandwich enzyme-linked immunosorbent assay (ELISA) for measurement of IgE antibodies to the bee venom allergens phospholipase A2 (PLA2) and hyaluronidase (HYAL). The assay is 10-20 times more sensitive than conventional indirect ELISA or radioallergosorbent test (RAST). Furthermore, by using affinity purified rabbit antibodies to these allergens, the specificity of the test was increased compared to RAST. The use of antibodies to link the antigen to the solid phase removes the dependence on the individual protein's ability to bind to the microtitre plate. The increased sensitivity of the sandwich assay seems to be due to better presentation and retention of antigen on the solid phase.


Brain vascularization in deep brain stimulation surgeries: epilepsy, Parkinson's disease, and obsessive-compulsive disorder.
In our experience, we encountered more blood vessels during deep brain stimulation (DBS) surgeries in epilepsy. In this study, we have quantified and compared the cerebral vascularization in epilepsy, Parkinson's disease (PD) and obsessive-compulsive disorder (OCD). A retrospective observational study in 15 epilepsy and 15 PD patients was performed. The amount, location, and size of blood vessels within 5 millimeters (mm) of all DBS electrode trajectories (N.=120) for both targets (anterior nucleus of the thalamus: ANT and subthalamic nucleus: STN) in both patient groups were quantified and compared on a Medtronic workstation (Dublin, Ireland). Additionally, blood vessels in the trajectories (N.=120) of another group of 15 PD (STN) and 15 OCD (ventral capsule-ventral striatum [VC-VS]) patients were quantified and compared (trajectories N.=120), also to the first group. Statistical analyses were performed with SPSS version 27.0 (descriptive statistics, independent samples t-tests, Mann Whitney U Test, ANOVA Test and post-hoc Tukey Test). A P value <0.05 was considered statistically significant. Our results showed a significant greater amount of cerebral blood vessels in epilepsy patients (10 SD±4) compared to PD (PD1 6 SD±1 and PD2 5 SD±3) and OCD (5 SD±1) with P<0.0001. Also, all other subanalyses showed more vascularization in the epilepsy group. Our results show that the brain of epilepsy patients seems to be more vascularized compared to PD and OCD patients. This can make the surgical planning for DBS more challenging, and the use of multiple trajectories limited.


Inferring the lifestyles of extinct Crocodyliformes using osteoderm ornamentation.
Osteoderms are bony plates formed within the dermis of diverse vertebrate groups. They are present in all crocodylomorphs but Metriorhynchidae. Most of them show typical bone ornamentation consisting of pits and ridges on their outer surface. The most widely discussed functional hypothesis suggests that the ornamentation of osteoderms influences heat exchange with the environment through the adjacent vascular network, facilitating the absorption of solar radiation. This process allows semiaquatic crocodiles to compensate for heat loss resulting from the high thermal conductivity of surrounding water. In order to test this assertion, we conducted a phylogenetic logistic regression analysis to evaluate the relationship between osteoderm relative area of pits (RAP) and lifestyle (terrestrial versus aquatic) in a sample of crocodyliforms. Our results revealed that lifestyle is significantly explained by RAP: the lower the degree of ornamentation (RAP), the higher the probability of a terrestrial lifestyle. We used this model to infer the lifestyle of two extinct taxa, Peirosaurus torminni and Microsuchus schilleri. We concluded that terrestrial notosuchians may have lost osteoderm ornamentation due to the lower thermal conductivity of air and reduced heat loss in a terrestrial environment compared to what happens in water. Among these notosuchians, we hypothesize that large terrestrial baurusuchids maintained a stable body temperature due to thermal inertia, whereas small notosuchians took advantage of the early morning sun exposure to warm up and stayed in terrestrial burrows during periods of intense solar radiation. Finally, unlike the almost motionless behavior of freshwater crocodiles, fully marine Metriorhynchidae probably lost osteoderms because they constantly swim, generating heat by muscular contraction, so osteoderms with a thermoregulatory function for heat absorption were no longer positively selected.


Experimentally determined chaotic phase synchronization in a neuronal system.
Mathematical analysis of the subthreshold oscillatory properties of inferior olivary neurons in vitro indicates that the oscillation is nonlinear and supports low dimensional chaotic dynamics. This property leads to the generation of complex functional states that can be attained rapidly via phase coherence that conform to the category of "generalized synchronization." Functionally, this translates into neuronal ensemble properties that can support maximum functional permissiveness and that rapidly can transform into robustly determined multicellular coherence.


Measuring information transfer in the spike generator of crayfish sustaining fibers.
We present a method based on information-theoretic distances for measuring the information transfer efficiency of voltage to impulse encoders. In response to light pulses, we simultaneously recorded the EPSP and spiking output of crayfish sustaining fibers. To measure the distance between analog EPSP responses, we developed a membrane noise model that accurately captures stimulus-induced nonstationarities. By comparing the EPSP and spike responses, we found encoding efficiencies on the order of 10(-4), with interesting dynamics occurring during initial transients. A simple analog to point-process converter predicted the small information transfer efficiencies and dynamic properties we measured.


Asymmetric cooperativity in tandem hybridization of enantiomeric metal complex-tethered short fluorescent DNA probes.
The complex [Ru(phen)(2)(dppz)](2+)(phen = 1,10-phenanthroline, dppz = dipyrido[3,2-aratio2',3'-c]phenazine) was attached to the 5' end of a short oligonucleotide to form conjugates, the Delta-isomer of which showed a high cooperativity during the recognition of the repetitive sequence, while the Lambda-isomer did not.


Effectiveness of impersonal versus interpersonal methods to recruit employees into a worksite quit smoking program.
One of the first salient issues a worksite quit smoking program must face is how to motivate employees to enroll and participate. The purpose of this study was to determine the effectiveness of impersonal versus interpersonal recruitment strategies used by an ongoing worksite quit smoking program. One hundred and nineteen smokers who stated on a questionnaire that they would be either "strongly yes" or "yes" interested in participating in a quit smoking program were randomized into two groups. One group was sent letters by employee mail from the director of the quit smoking program. This letter briefly described the program and invited employees to participate. The other group received a personal phone call from the staff health educator inviting them to participate. Results indicate that of the 46 individuals randomly assigned to Group 1 who were sent letters, none responded to the invitation; while 37 of the 44 employees who received a personal phone call, 19 scheduled an appointment, 7 kept their appointments. These results indicate the possible increased effectiveness of an impersonal versus interpersonal communications in recruiting full-time smoking employees.


A 'living' prosthetic iris.
To design and demonstrate dynamic pupils, which react to light for use with ocular prostheses. The realism of ocular prostheses is limited by the immobility of the pupil. Our solution is to use a liquid crystal display (LCD) in the prosthesis to vary the pupil size as a function of the ambient light. Several liquid crystal cells were fabricated and tested for survivability through the ocular prosthesis manufacturing process. The dynamic pupil is controlled by a novel and entirely autonomous, self-powered passive electronic circuit using a solar cell, matching the minimum diameter of the pupil. The first LCD surviving the rugged conditions of the ocular prosthesis manufacturing steps and an entirely passive circuit controlling the pupil have been demonstrated for the first time to our knowledge. A design for a complete prosthesis with a dynamic pupil has been proposed. Finally, a standard device for the mass production of ocular prostheses is presented. We have shown that a practical solution for an autonomous self-powered dynamic pupil is possible, given the constraints of size, fabrication process, weight, cost and manufacturability on a mass scale. We envision that the LCD could be mass produced, and only the final steps for the integration of the iris matched to a patient would be necessary before assembly using standard processing steps for the production of the prosthesis. Using a clinical trial, we hope to demonstrate that the dynamic pupil will have a positive impact on the quality of life of patients.


Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis.
Acute hemorrhagic leukoencephalitis is a fulminant demyelinating disease and commonly considered as a rare and severe variant of acute disseminated encephalomyelitis. Here, we report the clinical, magnetic resonance imaging, and brain biopsy findings of a 35-year-old female with relapsing-remitting multiple sclerosis, who developed acute hemorrhagic leukoencephalitis. Magnetic resonance imaging revealed symmetrical hemorrhagic lesions in the basal ganglia including the thalami. Disease progression was consistent with acute hemorrhagic leukoencephalitis with rapid deterioration of consciousness and seizures. Besides hemorrhage, infiltration of neutrophils was detected in brain biopsy.Acute hemorrhagic leukoencephalitis, also known as Weston-Hurst syndrome, is an excessive immunological response of unknown etiology. So far, an association with multiple sclerosis has not been reported. The present case raises the question, whether acute hemorrhagic leukoencephalitis is a specific hyperacute form of acute disseminated encephalomyelitis, a severe and unspecific form of an immune response in the central nervous system, or belongs to the spectrum of tumefactive multiple sclerosis.


Evaluation of a commercial enzyme immunoassay for detection of norovirus in outbreak specimens.
The aim of the study presented here was to use faeces from 41 gastroenteritis outbreaks (130 specimens) in Victoria, Australia, to evaluate the sensitivity and specificity of the RIDASCREEN norovirus enzyme immunoassay (EIA) kit relative to reverse transcription-polymerase chain reaction and/or electron microscopy. Seven specimens known to contain sapovirus, adenovirus, astrovirus and rotavirus were also tested. For single-specimen diagnosis the kit gave a specificity and sensitivity of 47% and 71%, respectively; altering the positivity cut-off to give a specificity of 73% reduced the sensitivity to 44%. Thus, the kit cannot be recommended for single-specimen diagnosis. One specimen containing adenovirus but not norovirus was identified as non-specifically positive by the EIA kit. If the criterion used for outbreak positivity was at least one EIA-positive specimen per outbreak, the kit's outbreak sensitivity was 94% but the outbreak specificity was only 60%.


S-phase independence of parathyroid hormone-induced calcium signalling in primary osteoblast-like cells.
Cell cycle-dependence of parathyroid hormone (PTH)-induced signal transduction was studied at the single cell level in fetal rat osteoblast-like cells (ROB) in primary culture. Responsiveness to 10(-7) M rPTH1-34 was measured as changes in the intracellular calcium concentration ([Ca2+]i) of cells loaded with Fura-2 using a video imaging setup. Cells in S-phase were identified by staining for incorporated 5-bromo-2'-deoxyuridine (BrdU). ROB were cultured on glass coverslips which had alphanumerically marked gratings so that cells could be located. Directly after measurement of the PTH-induced [Ca2+]i response of the individual cells, cells were fixed and stained for incorporated BrdU. Phase-contrast images taken with the video imaging setup were compared with phase-contrast micrographs and fluoro-micrographs taken after staining for BrdU incorporation. We found that 43% of the cells responding to PTH with a rise in [Ca2+]i had also incorporated BrdU. This percentage was not different from the percentage BrdU positive cells in the whole culture, showing that calcium responsiveness was randomly distributed between ROB in S-phase and those not in S-phase. We therefore conclude that PTH does not induce calcium responses preferentially during the S-phase of the cell cycle in ROB in primary culture.


APC/C CDH1 ubiquitinates STAT3 in mitosis.
STAT3, an oncogene drives tumor growth and is associated with poor prognosis. However, small molecule-based STAT3 inhibitors were unsuccessful in clinics. Recently, STAT3 degraders that ubiquitinate STAT3 were found to elicit long-lasting anti-tumor responses. Thus, triggering STAT3 ubiquitination in cancers is a better strategy than STAT3 inhibition. However, not much is known about the identity of E3-ligases that ubiquitinate STAT3 in cancers. Therefore, to design better therapies to degrade STAT3, we sought to identify E3-ligases that ubiquitinate STAT3 in cancer cells. To answer this question, we determined the cell cycle-dependent ubiquitination of STAT3 in HEK293T cells and examined the link between STAT3 dephosphorylation and ubiquitination. We found that STAT3 is more strongly ubiquitinated in mitosis than in other phases of the cell cycle. We observed that APC/C CDH1 binds and ubiquitinates STAT3 in mitosis. Further, we also found that inhibiting phosphatases decreases STAT3 ubiquitination. We conclude that APC/C CDH1 ubiquitinates STAT3 in mitosis. We suggest that mitosis can be a potential therapeutic window for treating STAT3-activated cancers.


Intracorporeal bi-directional pouch jejunojejunostomy following Roux-en-Y anastomosis: a simple reconstruction technique using an endoscopic linear stapler.
Intracorporeal pouch jejunojejunostomy (JJ) is a technically challenging procedure during totally laparoscopic gastrectomy (TLG). This study introduced a new method involving the construction of an intracorporeal bi-directional pouch JJ using an endoscopic linear stapler and analyzed the surgical outcomes of this method, including JJ complications. We retrospectively reviewed the medical records of 168 patients who underwent laparoscopic gastrectomy with intracorporeal bi-directional pouch JJ between November 2017 and October 2018 at Asan Medical Center. The construction of an intracorporeal bi-directional pouch JJ took an average of 10 min. No postoperative bleeding or anastomotic strictures related to JJ reconstruction occurred after this procedure. No mortality occurred during follow-up. Intracorporeal bi-directional pouch JJ using an endoscopic linear stapler is a safe and simple procedure. It is a feasible option to reduce JJ stricture after TLG in patients with gastric cancer.


Mechanical sensitivity of carotid body glomus cells.
Cultured glomus cells from rat carotid bodies were prepared for optical studies of intracellular calcium using the Fura-2 dye. The baseline calcium had a mean of about 40 nM showing either a relatively steady level or large calcium spikes. Some cells did not show measurable levels of [Ca(2+)](i). Stirring the fluid bathing the cultures induced large increases in [Ca(2+)](i) which were abolished when the bathing medium had zero Ca(2+) and EGTA. It is concluded that glomus cells respond to mechanical stimulation when directly exposed to this stimulus and are not protected by supporting structures. It is unknown if the electrical properties of these cells are also affected by mechanical challenges.


Clinical outcomes of mitral valve intervention in patients with mitral annular calcification: A systematic review and meta-analysis.
Mitral valve (MV) disease with mitral annular calcification (MAC) poses a surgical challenge and the clinical outcomes of MV surgery as well as transcatheter mitral valve replacement (TMVR) remain relatively unexplored. We performed a systematic review and meta-analysis to assess the effects of MAC on clinical outcomes following MV surgery and TMVR. We searched MEDLINE and EMBASE databases until February 2019 for studies comparing clinical outcomes of MV surgery or TMVR in patients with and without MAC. Data were extracted by two independent investigators. Outcomes were perioperative and midterm complications and mortality. Seven observational studies enrolling 2902 patients were included. MAC patients were older, more likely to be female with greater chronic lung disease and kidney failure. Perioperative mortality was similar between patients with and without MAC undergoing MV surgery (risk ratio [RR], 1.15; 95% confidence interval [CI], 0.50-2.65; P = .74). MAC was associated with a higher risk of bleeding, permanent pacemaker implantation, and periprosthetic leak. Midterm mortality was greater in MAC patients undergoing MV surgery (incident rate ratio [IRR], 1.32; 95% CI, 1.05-1.67; P = .02). MAC patients undergoing TMVR had higher perioperative (RR, 4.65; 95% CI, 2.93-7.38; P < .01) and 1-year (RR, 5.44; 95% CI, 3.49-8.49; P < .01) mortality, decreased procedural success, greater left ventricular outflow tract obstruction and need for conversion to surgery when compared with patients undergoing TMVR for dysfunction of a bioprosthetic valve or annuloplasty ring. MV procedures in patients with MAC are associated with higher mortality and morbidity. This is largely driven by the high-risk patient profile associated with MAC. TMVR holds promise but has important limitations and should be reserved for select patients.


Establishment of a method to expose and measure pollution in excised porcine skin with electron paramagnetic resonance spectroscopy.
Health problems associated with the amount of air pollutants are increasing worldwide. Pollution damages not only the lungs; it also has an impact on skin health and is co-responsible for the development of skin diseases. Anti-pollution products are on the rise in the cosmetic market but so far, there is no established method to directly assess the impact of pollution on the skin and to test the efficacy of anti-pollution products. To address this problem, two different chambers were developed for the reproducible exposure to realistic air pollutant concentrations. One chamber for the exclusive use of excised skin and hair samples, the second chamber for ex vivo and in vivo measurements. Measurements of nicotine next to the investigated skin area allow conclusions to be drawn on the particle concentration to which the skin is exposed. Electron paramagnetic resonance spectroscopy, which enables the detection of free radicals in different systems, was applied to assess the hazard potential of pollution in the skin. A direct proof of the formation of free radicals in the skin by the model pollutant cigarette smoke could be demonstrated. An additional application of UV irradiation even increased the formation of free radicals in the skin seven-fold (sum parameter). Depending on the question of interest, the use of different spin probes allows various assessments of the radical formation in skin: the amount of radicals but also the antioxidant status of the microenvironment can be estimated. Using two exposure chambers, the direct formation of oxidative stress by cigarette smoke on ex vivo skin, with and without additional UV exposure, could be reproducibly examined. This measurement method is promising for the assessment of anti-pollution products and could allow a direct causal connection between pollutant, effect on the skin and the protective function of skin care products.


Correction: SNV discovery and functional candidate gene identification for milk composition based on whole genome resequencing of Holstein bulls with extremely high and low breeding values.
[This corrects the article DOI: 10.1371/journal.pone.0220629.].


Accelerated arteriolar gas embolism reabsorption by an exogenous surfactant.
Cerebrovascular gas embolism can cause profound neurologic dysfunction, and there are few treatments. The authors tested the hypothesis that an exogenous surfactant can be delivered into the bloodstream to alter the air-blood interfacial mechanics of an intravascular gas embolism and produce bubble conformations, which favor more rapid bubble absorption. Microbubbles of air were injected into the rat cremaster microcirculation after intravascular administration of either saline (control, n = 5) or Dow Corning Antifoam 1510US (surfactant, n = 5). Embolism dimensions and dynamics were directly observed after entrapment using intravital microscopy. To achieve embolization, the surfactant group required twice as many injections as did controls (3.2 +/- 1.3 vs. 1.6 +/- 0.9; P < 0.05). There was no difference in the initial lodging configuration between groups. After bubble entrapment, there was significantly more local vasoconstriction in the surfactant group (24.2% average decrease in diameter) than in controls (3.4%; P < 0.05). This was accompanied by a 92.7% bubble elongation in the surfactant group versus 8.2% in controls (P < 0.05). Embolism shape change was coupled with surfactant-enhanced breakup into multiple smaller bubbles, which reabsorbed nearly 30% more rapidly than did parent bubbles in the control group (P < 0.05). Intravascular exogenous surfactant did not affect initial bubble conformation but dramatically increased bubble breakup and rate of reabsorption. This was evidenced by both the large shape change after entrapment and enhancement of bubble breakup in the surfactant group. These dynamic surfactant-induced changes increase the total embolism surface area and markedly accelerate bubble reabsorption.


Equine spermatozoal motility and fertility associated with the incorporation of d-(+)-mannose into semen extender.
Mannose is capable of decreasing bacterial attachment to the uterine mucosa in mares. Bacteria gain entry into the mare's uterus during breeding; therefore, a practical method to deliver mannose to the uterus is to incorporate it into semen extenders. The effect of mannose on spermatozoal motility and subsequent sperm fertilizing capability is unknown. The present study evaluated progressive spermatozoal motility in semen extender formulations incorporating mannose and assessed the fertility of mares inseminated with a mannose-containing semen extender. In Experiment 1, progressive spermatozoal motility in extender mixtures containing 0 mannose (control), 25, 37 or 49 mg/mL mannose was evaluated at 20 degrees C or 5 degrees C holding temperatures for 0, 12, 24 and 48 h post-dilution. Measures were repeated three times using five stallions of proven fertility. High concentrations of mannose in the extender affected progressive motility beyond the time and temperature effects noted in the controls. Extender containing only mannose sugar (49 mg/mL) displayed an immediate depression in progressive motility compared with controls (45.5% versus 62.9%, respectively; P<0.001). The 37 mg/mL mannose extender had a less dramatic decrease in motility (P<0.05) and only after storage at 5 degrees C for > or =12h (48.7% versus 58.0%, respectively). Extender with 25 mg/mL mannose performed no differently than the control formulation under all conditions. In Experiment 2, two groups of mares (n=11 each) were inseminated with 500 x 10(6) progressively motile spermatozoa extended in a traditional skim milk (control) extender or the 37 mg/mL mannose extender preparation. A single-cycle pregnancy rate of 72% was achieved by both groups. Present data suggest that a semen extender containing up to 37 mg/mL mannose could maintain motile spermatozoa for on-farm use and 25 mg/mL mannose concentrations preserved motility during long-term cooling. Likewise, sperm extended with up to 37 mg/mL of mannose had the same fertilizing capability as sperm in traditional extender mixtures.


CaviDB: a database of cavities and their features in the structural and conformational space of proteins.
Proteins are the structural, functional and evolutionary units of cells. On their surface, proteins are shaped into numerous depressions and protrusions that provide unique microenvironments for ligand binding and catalysis. The dynamics, size and chemical properties of these cavities are essential for a mechanistic understanding of protein function. Here, we present CaviDB, a novel database of cavities and their features in known protein structures. It integrates the results of commonly used cavity detection software with protein features derived from sequence, structural and functional analyses. Each protein in CaviDB is linked to its corresponding conformers, which also facilitates the study of conformational changes in cavities. Our initial release includes ∼927 773 distinct proteins, as well as the characterization of 36 136 869 cavities, of which 1 147 034 were predicted to be drug targets. The structural focus of CaviDB provides the ability to compare cavities and their properties from different conformational states of the protein. CaviDB not only aims to provide a comprehensive database that can be used for various aspects of drug design and discovery but also contributes to a better understanding of the fundamentals of protein structure-function relationships. With its unique approach, CaviDB represents an indispensable resource for the large community of bioinformaticians in particular and biologists in general. Database URL https://www.cavidb.org.


Childhood lead poisoning prevention through prenatal housing inspection and remediation in St. Louis, MO.
We assessed the screening and remediation of home lead hazards prenatally in a high-risk population, hypothesizing that average blood-lead level and the number of poisonings would drop by 25%. One hundred fifty-two women underwent prenatal home inspections by certified lead inspectors. The hazards that were identified were remediated. The blood-lead levels of children of participating women were compared with matched control subjects. Blood-lead levels were obtained from 60 children and compared with matched control subjects. The average blood-lead level of children in the treatment group was 2.70 μg/dL vs 3.73 μg/dL in control subjects (P = .019). The percentage of children with levels >10 μg/dL in the treatment group was 0% vs 4.2% in control subjects (P = .128). Screening and remediation of houses of pregnant women is effective to reduce the average blood-lead level and number of children that exceed the federal level of concern for lead poisoning in a high-risk population.


Metabolite mapping reveals severe widespread perturbation of multiple metabolic processes in Huntington's disease human brain.
Huntington's disease (HD) is a genetically-mediated neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein (Htt) through lengthening of its polyglutamine tract, thus initiating a cascade that ultimately leads to premature death. However, neurodegeneration typically manifests in HD only in middle age, and mechanisms linking the causative mutation to brain disease are poorly understood. Brain metabolism is severely perturbed in HD, and some studies have indicated a potential role for mutant Htt as a driver of these metabolic aberrations. Here, our objective was to determine the effects of HD on brain metabolism by measuring levels of polar metabolites in regions known to undergo varying degrees of damage. We performed gas-chromatography/mass spectrometry-based metabolomic analyses in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine matched controls. In each patient, we measured metabolite content in representative tissue-samples from eleven brain regions that display varying degrees of damage in HD, thus identifying the presence and abundance of 63 different metabolites from several molecular classes, including carbohydrates, amino acids, nucleosides, and neurotransmitters. Robust alterations in regional brain-metabolite abundances were observed in HD patients: these included changes in levels of small molecules that play important roles as intermediates in the tricarboxylic-acid and urea cycles, and amino-acid metabolism. Our findings point to widespread disruption of brain metabolism and indicate a complex phenotype beyond the gradient of neuropathologic damage observed in HD brain.


A Genome-Wide Association Study Identifying Genetic Variants Associated with Growth, Carcass and Meat Quality Traits in Rabbits.
Growth, carcass characteristics and meat quality are the most important traits used in the rabbit industry. Identification of the candidate markers and genes significantly associated with these traits will be beneficial in rabbit breeding. In this study, we enrolled 465 rabbits, including 16 male Californian rabbits and 17 female Kangda5 line rabbits as the parental generation, along with their offspring (232 male and 200 female), in a genome-wide association study (GWAS) based on SLAF-seq technology. Bodyweight at 35, 42, 49, 56, 63 and 70 d was recorded for growth traits; and slaughter liveweight (84 d) and dressing out percentage were measured as carcass traits; and cooking loss and drip loss were measured as meat quality traits. A total of 5,223,720 SLAF markers were obtained by digesting the rabbit genome using RsaI + EcoRV-HF® restriction enzymes. After quality control, a subset of 317,503 annotated single-nucleotide polymorphisms (SNPs) was retained for subsequent analysis. A total of 28, 81 and 10 SNPs for growth, carcass and meat quality traits, respectively, were identified based on genome-wide significance (p < 3.16 × 10-7). Additionally, 16, 71 and 9 candidate genes were identified within 100 kb upstream or downstream of these SNPs. Further analysis is required to determine the biological roles of these candidate genes in determining rabbit growth, carcass traits and meat quality.


Syndemics theory must take local context seriously: An example of measures for poverty, mental health, and food insecurity.
Syndemics theory has provided insight into the ways that disease states and social adversity interact in marginalized populations to further disempower these groups. Yet, until recently, scholars have not identified how we might actually recognize and measure a syndemic, as opposed to a situation where there are multiple but non-interacting diseases present in a population. As researchers like those included in this special issue develop new methods for assessing syndemic interactions in diverse global populations, this short communication argues for the value of locally relevant measures. Poverty, mental health, food insecurity, and type 2 diabetes are used to illustrate the assessment of a potential syndemic from a locally grounded perspective. The discussion emphasizes the insights locally adapted measures can add and what information would be lost without their use.


[Prognostic value of color Doppler ultrasonography of the thyroid gland in autoimmune thyroiditis].
91 patients with chronic autoimmune thyroiditis have been examined. The obtained results showed considerable increase in resistance index in patients with hypothyroidism. It may be used as a prognostic criterion of the development of hypothyroidism.


Comparison of psychosocial adaptations among childhood cancer survivors, their siblings and peers in Taiwan.
This study aimed to understand the difference in psychosocial adaptation among childhood cancer survivors, their healthy siblings and peers, and the factors affecting the psychosocial adaptation of these cancer survivors. A total of 222 children (ages 8-17) including childhood cancer survivors, their siblings, and healthy peers participated in this cross-sectional study. All the children completed the anxiety and quality of life scales for their age groups. Anxiety levels and quality of life were similar among the childhood cancer survivors, their siblings, and their peers. The anxiety of elementary school-age survivors of acute leukemia was higher than that of those with solid tumors. Elementary school-age survivors who completed three or more years of treatment had lower anxiety than those who completed treatment within the three years. For adolescent survivors, the higher their body mass index, the higher their anxiety, which was associated with low quality of life. Those diagnosed with anxiety and at an older age had lower quality of life. Although there were no differences in survivors' psychosocial adaptation compared to their siblings and healthy peers, more than half of these adolescents had moderate to severe anxiety. Future study may need to explore the causes of their anxiety. During the follow-ups of the childhood cancer survivors, age-specific adaptive strategies can be discussed to reduce their anxiety and improve their quality of life.


Production and characterization of monoclonal antibodies against secretory proteinase of Candida albicans CBS 2730.
We describe the production and characterization of three murine monoclonal antibodies (M1-M3) which are directed against different epitopes of the secretory aspartic proteinase of Candida albicans CBS 2730. All antibodies belonged to the IgM class, and they recognized denatured enzyme. Only antibody M1 was capable to react with the active proteinase. Differential reactivity was also observed with a large fragment of the proteinase of C. albicans. All antibodies recognized the corresponding proteinase of C. tropicalis 293 both in the active, and in the denatured state. Denatured porcine pepsin was also recognized by all three antibodies. However, active pepsin was recognized only by antibodies M1 and M2. The antibodies did not inhibit enzymatic activity, and they were not suited for immunofluorescence detection of proteinase on fungal cells. However, employing Western blot analysis, proteinase antigen was detected by antibody M 1 in the serum of a patient suffering from candidal pneumonia. The circulating proteinase antigen was found to be bound to patient's IgM. Implications for the use of monoclonal antibodies in the serodiagnosis of candidosis, and first experiences with other monoclonal anti-proteinase antibodies are discussed.


Purification and characterization of equine complement factor C3.
A rapid method for purifying equine C3 which yields milligram quantities of pure C3 is described. Protein from equine plasma was selectively precipitated with polyethylene glycol, and the C3 was purified by anionic and cationic exchange HPLC. The yield from this procedure was 12%. The purified C3 was composed of an alpha chain (118 kD) and a beta chain (68 kD) linked by at least one disulfide bond, and it had an isoelectric point of 4.7. Amino acid analysis indicated a strong conservation of amino acid usage between equine and human C3. The N-terminal sequences of the alpha and beta chains were homologous to human, mouse, and rat C3, and activation of C3 produced breakdown products similar in molecular weight to C3b and iC3b of other species. Equine C3 appeared to be functionally dependent upon a reactive thiolester as treatment of fresh equine serum with methylamine abrogated its hemolytic activity.


Correlation between sedentary activity, physical activity and bone mineral density and fat in America: National Health and Nutrition Examination Survey, 2011-2018.
We compared the relationship between sedentary activity (SA) and physical activity (PA) with bone mineral density (BMD) and body fat percentage in the United States and found a negative association between SA and BMD and a positive association with body fat percentage. A positive association between PA and BMD and a negative association with body fat percentage. SA and PA are associated with changes in skeletal parameters and body fat percentage, and we aimed to investigate and compare the relationship between SA, PA and bone mineral density (BMD) and body fat percentage in men and women. We assessed the relationship between SA, PA and BMD and body fat percentage in 9787 Americans aged 20-59 years (mean age 38.28 ± 11.39 years) from NHANES 2011-2018. BMD and body fat percentage were measured by dual-energy X-ray bone densitometry (DXA). We used multiple linear regression models to examine the relationships between SA, PA and lumbar spine BMD and total body fat percentage, adjusted for a large number of confounding factors. After adjusting for race/ethnicity, age, alcohol and smoking behavior, body mass index (BMI), total protein, blood calcium, blood uric acid, cholesterol, blood phosphorus, vitamin D, and blood urea nitrogen, SA was negatively associated with lumbar spine BMD (β = - 0.0011 95% CI - 0.0020 to - 0.0002, P = 0.022), and SA was positively associated with total fat percentage (β = PA was positively associated with lumbar BMD (β = 0.0046 95% CI 0.0010 to 0.0082, P = 0.012) and there was a negative association between PA and body fat percentage (β = - 1.177 95% CI - 1.326 to -1.027, P < 0.001). Our results show that physical activity is a key component of maintaining bone health in both men and women and is strongly associated with lower body fat percentages. Sedentary activity is negatively correlated with bone density and is strongly associated with an increase in body fat percentage. Healthcare policy makers should consider reducing sedentary activity and increasing physical activity when preventing osteoporosis and obesity.


Immune-modulatory drugs alter Candida albicans-induced sleep patterns in rabbits.
To evaluate the influences of immune responsiveness on sleep alteration during infectious disease, sleep was monitored during Candida albicans infection in rabbits treated with immune-modulating drugs. Intravenous administration of C. albicans to normal rabbits initially increased and subsequently decreased both the amount of slow-wave sleep (SWS) and delta-wave amplitudes (DWA) during SWS. Cortisone treatment attenuated these effects. The immunosuppressive drug cyclosporine did not alter the initial enhancement of SWS, but did attenuate the C. albicans-induced reduction in SWS time and potentiate the reduction in DWA. In contrast, administration of incomplete Freund's adjuvant and prior immunization with killed C. albicans, which were expected to enhance immune responsiveness, did not markedly alter C. albicans-induced alterations in SWS. However, the immune stimulant levamisole potentiated the effects of C. albicans on SWS. These data indicate that pharmacologic treatments expected to alter immune responsiveness modulate microbially induced sleep, and are consistent with the hypothesis that facets of the immune response mediate sleep changes during infectious disease.


Thrombopoietin stimulates proliferation and megakaryocytic differentiation of mouse pro-B cell line BF-TE22.
We have isolated and characterized a thrombopoietin (TPO)-dependent BF-TE22 cell line endogenously expressing murine Mpl, which is a subclone of murine pro-B Ba/F3 cells. TPO stimulated the proliferation of BF-TE22 cells in a dose-dependent manner, and also induced the expression of megakaryocyte lineage-specific AP-51 and CD61 cell surface antigens. The results indicate that the murine Mpl on BF-TE22 cells can transmit both proliferation and megakaryocyte lineage-specific differentiation signals to cells. Furthermore, it was shown that IL-3 inhibits the TPO-induced differentiation signals of BF-TE22 cells. These results suggest that the signals mediated by IL-3 predominate over those of TPO in BF-TE22 cells. Thus, BF-TE22 cells will be useful for the biological and biochemical studies of the TPO-Mpl signal transduction mechanism.


Pharmacist independent prescribing in secondary care: opportunities and challenges.
In recent years a number of countries have extended prescribing rights to pharmacists in a variety of formats. The latter includes independent prescribing, which is a developing area of practice for pharmacists in secondary care. Potential opportunities presented by wide scale implementation of pharmacist prescribing in secondary care include improved prescribing safety, more efficient pharmacist medication reviews, increased scope of practice with greater pharmacist integration into acute patient care pathways and enhanced professional or job satisfaction. However, notable challenges remain and these need to be acknowledged and addressed if a pharmacist prescribing is to develop sufficiently within developing healthcare systems. These barriers can be broadly categorised as lack of support (financial and time resources), medical staff acceptance and the pharmacy profession itself (adoption, implementation strategy, research resources, second pharmacist clinical check). Larger multicentre studies that investigate the contribution of hospital-based pharmacist prescribers to medicines optimisation and patient-related outcomes are still needed. Furthermore, a strategic approach from the pharmacy profession and leadership is required to ensure that pharmacist prescribers are fully integrated into future healthcare service and workforce strategies.


Optimization of electroporation for transfection of human fibroblast cell lines with origin-defective SV40 DNA: development of human transformed fibroblast cell lines with mucopolysaccharidoses (I-VII)
To simplify the process of transfection of human fibroblasts and to acquire a suitable number of transformants, we investigated experimental conditions of electric pulse-induced transfection of human fibroblasts using origin-defective simian virus 40 DNA (SV40 (ori-) DNA). Voltage, pulse duration, number of pulses and the concentration of SV40 (ori-) DNA led to the formation of 10 to 30 foci/25 cm2 6 weeks after transfection, using 2 to 3 x 10(6) cells and a square wave pulse generator. Optimal condition was determined to be 2 or 3 pulses at a voltage of 1500 to 2000 V/0.4 cm with 30 microseconds pulse width, using 2 micrograms of linearized SV40 (ori-) DNA. With this approach we developed human transformed fibroblasts cell lines with all types of mucopolysaccharidoses. The transformed fibroblasts grew rapidly and the saturation density exceeded that of the parental cells. All the transformed cell clones expressed T antigen, and deficiency in specific enzymes was conserved. A point mutation which occurred in the human beta-glucuronidase gene in a patient with mucopolysaccharidosis type VII was also conserved.


High levels of third-stage larvae (L3) overwinter survival for multiple cattle gastrointestinal nematode species on western Canadian pastures as revealed by ITS2 rDNA metabarcoding.
The ability of infective larvae of cattle gastrointestinal nematode (GIN) species to overwinter on pastures in northerly climatic zones with very cold dry winters is poorly understood. This is an important knowledge gap with critical implications for parasite risk assessment and control. Infective third-stage larvae (L3) were quantified in samples of fecal pats, together with adjacent grass and soil, before and after winter on three farms in southern, central and northern Alberta. Nemabiome ITS2 metabarcoding was then performed on the harvested L3 populations to determine the species composition. Finally, parasite-free tracer calves were used to investigate if the L3 surviving the winter could infect calves and develop to adult worms in spring. Farm level monitoring, using solar powered weather stations, revealed that ground temperatures were consistently higher, and less variable, than the air temperatures; minimum winter air and ground temperatures were - 32.5 °C and - 24.7 °C respectively. In spite of the extremely low minimum temperatures reached, L3 were recovered from fecal pats and grass before and after winter with only a 38% and 61% overall reduction over the winter, respectively. Nemabiome ITS2 metabarcoding assay revealed that the proportion of L3 surviving the winter was high for both Cooperia oncophora and Ostertagia ostertagi although survival of the former species was statistically significantly higher than the latter. Nematodirus helvetinaus and Trichostrongylus axei could be detected after winter whereas Haemonchus placei L3 could not overwinter at all. Adult C. oncophora, O. ostertagi and N. helvetianus could be recovered from tracer calves grazing after the winter. The largest proportion of L3 were recovered from fecal pats suggesting this is important refuge for L3 survival. Results also show that L3 of several GIN parasite species can survive relatively efficiently on pastures even in the extreme winter conditions in western Canada. Tracer calf experiments confirmed that overwintered L3 of both C. oncophora and O. ostertagi were capable of establishing a patent infection in the following spring. These results have important implications for the epidemiology, risk of production impact and the design of effective control strategies. The work also illustrates the value of applying ITS2 nemabiome metabarcoding to environmental samples.


[Osseous avulsion of the opponens pollicis muscle. Case report of a rare injury in skiing].
Two cases in which the M. opponens pollicis was ruptured with a bony fragment are reported. In each case the injury, which occurred in young people (24-29 years of age), was the outcome of a fall during alpine skiing, whereby the hand hit the icy slope. Operative treatment was necessary due to the intense subjective pain which followed a significant thenar hematoma.


["Mechanization of death"-The crematorium of Ueckermünde mental institution during National Socialism].
The intensity of the research undertaken in recent decades into the killing of the sick during the Nazi period has produced a wealth of publications that will have a long-reaching impact; however, gaps in the research remain, both at regional level and with regard to the national campaign. This article focuses on the region of Pomerania, which in a whole range of ways followed its own course in the extermination of mentally ill and disabled people. It sheds light on a feature of the psychiatric landscape under the Nazis which has drawn little attention to date: the construction of the first crematorium within an asylum in the Third Reich, in 1940 in Ueckermünde. On the basis of archive material explored here for the first time, the role of the crematorium in the killing of the sick on a regional level is discussed, as is its link to the organizers of the centralized T4 campaign in Berlin. The article asks whether and to what extent there was, during the early phase of the "euthanasia" killings, a parallel regionally initiated extermination operation targeting the sick, and whether and to what extent this was tolerated or even supported by Berlin. It also provides interesting insights into the "knowledge transfer" between the head of the Ueckermünde asylum Hans-Dietrich Hilweg and the head of the asylum in Kaufbeuren, Bavaria, Valentin Faltlhauser, on how best to hide or minimize the traces of the murders. These insights clearly exemplify the transformation process postulated by Ernst Fraenkel from a normative state to a prerogative state.


Application of linear discriminant analysis to the biochemical and haematological differentiation of opiate addicts from healthy subjects: a case-control study.
Biochemical and haematological parameters of nutritional interest were determined in the serum of opiate addicts in order to compare them with those obtained in healthy subjects. Linear discriminant analysis was applied for the differentiation of the opiate addicts. Sera of 106 opiate addicts in detoxification treatment (n=19) or in Methadone Maintenance Treatment Program (MMTP) (n=87) were studied. : The determination of classical biochemical and haematological parameters in blood samples was carried out using standardized methods. Determination of retinol and alpha-tocopherol was carried out by high-performance liquid chromatography with diode-array detector. Folic acid and vitamin B(12) were determined using competitive binding techniques. Minerals were determined by flame emission spectrometry (Na and K) and atomic absorption spectrometry with air-acetylene flame (Ca, Mg, Fe, Cu and Zn) or with hydride generation (Se). Phosphorous was determined using a colorimetric method with ammonium molibdate. All statistical analyses were performed by means of the SPSS version 10.0 software for Windows. Stepwise linear discriminant analysis simplified the system to the following variables: Na, K, Mg, number of leucocytes, triglycerides, GPT, glucose, albumin, retinol and folic acid; and 90.1% (86.4% after crossvalidation) of correct classification was obtained. Representing the first and second discriminant functions, the control groups were well separated from opiate addicts. Applying linear discriminant analysis on several biochemical and haematological parameters, the opiate addicts could clearly be differentiated from the control individuals, and a tendency to differentiate the opiate addicts in MMTP and in detoxification treatment was observed.


Opportunity Cost and Policy: A Utilization Review of Self-monitoring of Blood Glucose in Manitoba, Canada.
Recently, there has been a re-evaluation of the frequency, benefits, and costs associated with self-monitoring of blood glucose (SMBG). Based on little evidence of the benefit of frequent SMBG in patients with diabetes not using insulin, new guidelines and test strip limit policies have been suggested and implemented in various Canadian jurisdictions to promote a more selective practice of SMBG. The objective of this study was to assess the overall utilization and cost associated with test strips and lancets for SMBG in Manitoba from 2000 to 2013 as well as to explore the policy implications of the implementation of test strip quantity limits and its impact on overall and government costs. An analysis of prescription claims for blood glucose test strips (BGTSs) and lancets for all patients with diabetes in Manitoba from 2000 to 2013 was conducted. In each year, patients were stratified into 4 mutually exclusive hierarchical groups according to most intensive diabetes treatment. Test strip and lancet utilization and cost were assessed for each group in each year, and the potential cost savings associated with implementation of a BGTS limit policy was projected using autoregressive integrated moving average models. In the year 2000, 8 million test strips were dispensed in Manitoba, increasing by 170% to 21.7 million test strips in 2013. Insulin users accounted for the majority of test strip use. However, based on potential implementation of test strip limit policies, 95% of the reduction of test strip use is predicted to occur in the groups not using insulin. Based on current trends, the 5-year predicted additional cost associated with not implementing a test strip limit policy similar to that implemented in other Canadian provinces was estimated to be a total of $12.35 million. Implementation of the guideline-based policy limits is predicted to produce considerable savings, with 95% of potential savings occurring in patients not using insulin. There is, therefore, a significant opportunity cost associated with not implementing a policy to reduce BGTS utilization by patients with diabetes in Manitoba. Based on the lack of evidence to suggest significant outcome improvements with long-term frequent SMBG by patients not using insulin, more selective use of test strips for SMBG could allow for significant cost savings that could be redirected to other programs and interventions for the growing population of patients with diabetes in Manitoba.


Predictors of successful outcomes in first web space contracture release.
The success of a first web space contracture release is dependent on the individual parameters of thumb movement. Examining these parameters individually, it is possible to predict which components are important for providing successful outcomes. We identified all patients who underwent a first web space contracture release over 7 years. Patients were examined for the following: radial abduction-abduction of the thumb in the plane of the hand; palmar abduction-abduction of the thumb 90° to the plane of the hand; and opposition-distance between first and fifth palmar digital crease. Measurements were compared between affected and unaffected hands, and correlations between components and patients' Disability of the Arm, Shoulder, and Hand (DASH) scores were determined. Thirty-nine patients underwent release of a first web space contracture; 11 agreed to participate. Opposition distance was significantly greater in the affected hand than in the unaffected hand. Grip strength was significantly lower in the affected hand. There were no significant differences in the radial or palmer abduction angles between hands. There was a moderate relationship between opposition distance and DASH score. There was no relationship between DASH and the other physical measurements. It is possible to obtain normal radial and palmar abduction angles after first web space release; however, success is not dependent on these absolute angles of abduction. Success of a release is related to the amount of opposition obtained, and it is difficult to achieve equivalent opposition to the unaffected hand. Grip strength and opposition remain decreased following contracture release.


An analysis of cocaine effects on locomotor activities and heart rate in four inbred mouse strains.
The effects of cocaine on Y-maze activity and heart rate have been examined in four inbred strains of mouse (BALB, C57BL, C3H and DBA). In addition, brain [3H]-cocaine concentrations were measured at the time of maximal response to cocaine. Cocaine produced a dose-related increase in Y-maze cross activity in C3H, DBA and C57BL, with C3H mice being considerably more sensitive than DBA or C57BL. Cocaine was without effect on Y-maze cross activity in BALB mice. Cocaine produced a biphasic effect on rearing activity in C3H mice, a dose related depression in BALB mice, and was without effect on C57BL and DBA mice. At the highest dose studied (15 mg/kg), cocaine produced a small decrease in heart rate in C3H mice. Strain differences in behavior were maximal 15 minutes after a dose of 5 mg/kg, IP. At this dose and time interval, brain [3H]-cocaine concentrations were not significantly different among the four strains of mice. The results suggest a genetically-determined difference in CNS sensitivity to cocaine.


SARS-CoV-2 and cardiovascular complications: From molecular mechanisms to pharmaceutical management.
The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.


Towards improved health service quality in Tanzania: contribution of a supportive supervision approach to increased quality of primary healthcare.
Universal Health Coverage only leads to the desired health outcomes if quality of health services is ensured. In Tanzania, quality has been a major concern for many years, including the problem of ineffective and inadequate routine supportive supervision of healthcare providers by council health management teams. To address this, we developed and assessed an approach to improve quality of primary healthcare through enhanced routine supportive supervision. Mixed methods were used, combining trends of quantitative quality of care measurements with qualitative data mainly collected through in-depth interviews. The former allowed for identification of drivers of quality improvements and the latter investigated the perceived contribution of the new supportive supervision approach to these improvements. The results showed that the new approach managed to address quality issues that could be solved either solely by the healthcare provider, or in collaboration with the council. The new approach was able to improve and maintain crucial primary healthcare quality standards across different health facility level and owner categories in various contexts. Together with other findings reported in companion papers, we could show that the new supportive supervision approach not only served to assess quality of primary healthcare, but also to improve and maintain crucial primary healthcare quality standards. The new approach therefore presents a powerful tool to support, guide and drive quality improvement measures within council. It can thus be considered a suitable option to make routine supportive supervision more effective and adequate.


Hypoxemia correlates with attentional dysfunction in patients with obstructive sleep apnea.
Obstructive sleep apnea is associated with cognitive impairment, but whether hypoxemia or repeated arousals and sleepiness are the underlying mechanism is controversial. Studies using a wide range of attention and executive functions tests in patients with severe sleep apnea are lacking. In a prospective cohort study, 40 patients aged 30-70 years, diagnosed with obstructive sleep apnea (apnea-hypopnea index ≥5) were recruited. Patients with known cardiovascular, pulmonary, psychiatric, or neurological disease, and or patients receiving anti-psychotic, sedatives, or stimulant medications were excluded. Patients underwent full overnight polysomnography including continuous oxygen saturation measurements followed by extensive neuropsychological testings in attention and executive function domains. The correlation between sleep apnea severity and patients' performance on the neuropsychological tests was examined. The patients' performance on measures of attention and executive function was significantly worse compared to the average in a normal population. Attention, as reflected by the number of omissions and by the reaction time on the Conners' Continuous Performance Test correlated significantly with the apnea-hypopnea index (r = 0.6, p < 0.001 and r = 0.48, p = 0.003, respectively) and with parameters of hypoxemia, namely the average SpO(2) (r = -0.51, p = 0.002 and r = -0.39, p = 0.02, respectively) and the percent time spent with SpO(2) < 90% (r = 0.57, p < 0.001 and r = 0.39, p = 0.02, respectively), but not with the degree of sleepiness. Executive dysfunction did not correlate with sleep parameters. Attention is the predominant cognitive function affected in patients with obstructive sleep apnea and correlates primarily with nocturnal hypoxemia rather than daytime sleepiness or sleep fragmentation. Executive functions, while below average in some patients, do not correlate with polysomnographic parameters.


Semantic abilities in dementia of the Alzheimer type. II. Grammatical semantics.
The grammatical semantic abilities of 18 Alzheimer patients were investigated using picture description tasks and compared to those of a group of institutionalized, nonneurologically impaired control subjects matched for age, sex, and educational level. During picture description, Alzheimer patients showed that they were able to provide as much information about the target picture as control subjects, but were less concise in their verbal representation of the information. The lack of conciseness was reflected in the DAT patients requiring more time and more syllables to communicate a similar quantity of information than the control subjects. The appropriateness of using a picture description task which involves a perceptual step-by-step account of unrelated events to assess sentential semantics and the conveying of information at a conceptual level is discussed.


Studies of secretory IgA in caries-resistant and caries-susceptible adults.
Caries resistant subjects appeared to possess a greater potential for production of secretory IgA than caries susceptible subjects, at least in stimulated parotid and submaxillary secretions. There was considerable overlap, however, among subjects in all groups examined. There are no consistent differences in s-IgA among groups in unstimulated parotid and submaxillary saliva. It would appear, therefore, that s-IgA secretion per se is not a critical determinant of caries resistance. The tendency to higher s-IgA values among resistant people, however, may indicate a greater propensity to specific antibody production. This aspect of caries protection requires independent investigation.


The effects of dopaminergic blocking agents on the glucose tolerance test in 6 humans and 6 dogs.
Pre-treatment with low doses of sulpiride, an atypical dopaminergic blocking agent, but not haloperidol, a classical dopaminergic blocking agent, decreased tolerance to glucose and increased blood serotonin levels in 6 normal humans and 6 normal dogs investigated.


Use of Postpartum Magnetic Resonance Imaging for Diagnosis and Classification of Retained Placenta Tissue.
To study the potential application of magnetic resonance imaging (MRI) for classification of retained placental tissue (RPT) in the uterus postnatally. Twenty-two patients with clinically or pathologically proven RPT were studied. The thickness ratio (D1/D2) of invaded (D1) to normal (D2) myometrium could be categorized into 3 groups (>0.6, 0.1-0.6, and <0.1) correlating with the 3 types of RPT: accreta vera (RPA), increta (RPI), and percreta (RPP) (r = -0.861, P < 0.01). After uterine arterial embolization, the RPT showed lower signal intensity than the myometrium without flow voids on T2-weighted images. Two cases of RPP showed gradual enhancement, except 1 case of infection and 2 cases that did not involve enhancement examinations, whereas 17 cases of RPA and RPI showed early enhancement. Magnetic resonance imaging can facilitate diagnosis of RPT severity. Dynamic contrast enhancement can indicate RPT activity and blood supply, thereby ensuring appropriate clinical decision making.


Conventional approach x laparoscopic abdominoperineal resection for rectal cancer treatment after neoadjuvant chemoradiation: results of a prospective randomized trial.
The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation. Twenty eight patients with distal rectal adenocarcinoma were randomized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospectively. Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach. There was no significant difference (p<0,05) between the two studied groups regarding: gender, age, body mass index, patients with previous abdominal surgeries, intra and post operative complications, need for blood transfusion, hospital stay after surgery, length of resected segment and pathological staging. Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach (p=0.04). Mean anesthesia duration was shorter (p=0.03) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes, respectively. There was no need for conversion to open approach in this series. After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery, local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group. We conclude that laparoscopic abdominoperineal resection is feasible, similar to conventional approach concerning surgery duration, intra operative morbidity, blood requirements and post operative morbidity. Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer.


Induction of Type 2 Diabetes in Mice to Understand Vascular Changes That Drive Diabetic Retinopathy.
Diabetic retinopathy is a common complication of type 2 diabetes. Research into this comorbidity is challenging due to the slow progression of pathological changes and the limited transgenic models available to study disease progression and mechanistic changes. Here, we describe a non-transgenic mouse model of accelerated type 2 diabetes using a high-fat diet in combination with streptozotocin delivered via osmotic mini pump. This model, when subjected to fluorescent gelatin vascular casting, can be used to study vascular changes in type 2 diabetic retinopathy.


Spinal osteoblastoma: a retrospective study of 35 patients' imaging findings with an emphasis on MRI.
To investigate the values of multimodal imaging approaches in the diagnosis of spinal osteoblastomas with an emphasis on MRI findings. We retrospectively evaluated the imaging findings of 35 patients with spinal osteoblastomas. The imaging methods included radiography, whole-body bone scintigraphy (WBBS), CT and MRI. Radiography detected 87.1% (27/31) of the lesions; WBBS demonstrated increased radionuclide activity in all the lesions. CT could precisely show and localize all niduses, and calcification was always detected. MRI usually could adequately delineate the niduses of osteoblastomas, especially on T2WI (88.2%; 30/34). 71.9% (23/32) of osteoblastomas were surrounded with moderate or extensive bone marrow edema (BME) with soft tissue edema (STE). STE always extended along the muscle bundle adjacent to the lesion; there was no subcutaneous fat involvement. BME was eccentrically distributed in the vertebral body and spread inward from the sides of the nidus. The extent of BME in the vertebral body tended to be inversely proportional to the distance from the nidus. In addition, rare magnifications of osteoblastoma including multifocal diseases (n = 2), vertebra plana (n = 1) or with aneurysmal bone cysts (n = 6) were also observed in our study. In patients showing moderate or extensive BME together with STE on MRI, both CT and MRI should be used to confirm nidus presence. The above-mentioned characteristics of edema on MRI of patients with spinal osteoblastoma are helpful in not only localizing the nidus, but also enhancing the diagnostic confidence.


Should we estimate liver span in the right mid-clavicular line or the midline?
Comparison was made between the accuracy of repeated measurements of liver projection below the costal margin in the right mid-clavicular line (RMCL) and in the midline (ML). Clinical measurement of liver span was studied in 34 children under 5 years of age by five members of junior ward staff. Three patients were followed longitudinally by the same observers. The coefficient of reliability between different observers for measurement in the RMCL was 13 mm but for that in the ML was 7 mm. Estimates of liver size in the RMCL were particularly inaccurate when examining larger livers. More reliable sequential estimates of liver size are likely to be obtained using measurements both in the midline and in a well-defined and agreed point below the right costal margin.


A longitudinal study of semen quality in pesticide spraying Danish farmers. The ASCLEPIOS Study Group.
It was hypothesized that occupational exposure to pesticides during a spraying season causes changes in semen quality that might be detected in a longitudinal study. We analyzed the within-person changes in semen quality and reproductive hormones across a spraying season in groups of farmers using and not using pesticides. A total of 248 men collected two semen samples (participation rate: 32%). The median sperm concentration declined significantly from the first to the second sample in both groups, but there was no statistical difference in the decline between the two groups, unadjusted or adjusted. Only minor changes were found in sperm morphology, vitality, motility, sperm chromatin denaturation (SCSA), and reproductive hormones, and the differences in changes between the two groups were nonsignificant, or, in the opposite direction to the expected. There was no relation between the changes in sperm parameters in relation to pesticide exposure variables. In conclusion, use of pesticides by Danish farmers is not a likely cause of short-term effects on semen quality and reproductive hormones.


"Aggressive" chondroblastoma. Light and ultramicroscopic findings after en bloc resection.
A chondroblastoma of the proximal humerus in a 15-year-old boy was removed en bloc due to its very large size and locally destructive, aggressive character. This case is reported because of the rarity of chondroblastomas excised en bloc; specimens were examined in detail by correlated roentgenographic, gross inspection, histologic and electron-microscopic methods.


Covert Task Embedding: Turning a DNN Into an Insider Agent Leaking Out Private Information.
We present the covert task embedding (CTE) attack, a new general threat affecting deep neural networks (DNNs). The new attack consists in hiding a malicious privacy-sensitive task within a seemingly innocuous network, in such a way that the result of the malicious task is delivered together with the legitimate output in a stealthy way. The result of the covert task is further protected by requiring that its extraction depends on a secret key shared by the embedder and the detector. We demonstrate the feasibility of the CTE attack in various settings, wherein a face-based age estimation DNN is trained in such a way as to also detect the gender (binary classification task) or ethnicity (multiclassification task) of the framed individual and stealthily pass along such information together with the estimated age. The results of the experiments we carried out show that, in all cases, the gender and ethnicity information can be reliably extracted without impairing the accuracy of the age estimation functionality. Despite the simplicity of the estting considered in the brief, our experiments show the feasibility of the CTE attack, thus calling for the development of suitable remedies against it.


Iatrogenic Interval Gangrene of the Thigh.
Interval gangrene of the thigh is an extremely rare complication in vascular surgery. Most cases have reported interval gangrene of the calf as a consequence of a distal bypass procedure, with little documentation of interval thigh gangrene occurring after endovascular intervention. The present case suggests that in the process of placing multiple-level covered and bare metal stents in the iliac, superficial femoral, and popliteal arteries, interval gangrene of the thigh must be considered as a potential, albeit rare, complication. Preservation of pelvic and profunda femoris flow to the thigh is imperative to prevent the development of interval tissue loss. This case demonstrates the importance of maintaining profunda femoris circulation, especially in patients with significant vascular comorbidities. Patient consent was obtained for details of the case to be used for publication.


Comparison between dedicated MRI and symphyseal fluoroscopic guided contrast agent injection in the diagnosis of cleft sign in athletic groin pain and association with pelvic ring instability.
To compare dedicated MRI with targeted fluoroscopic guided symphyseal contrast agent injection regarding the assessment of symphyseal cleft signs in men with athletic groin pain and assessment of radiographic pelvic ring instability. Sixty-six athletic men were prospectively included after an initial clinical examination by an experienced surgeon using a standardized procedure. Diagnostic fluoroscopic symphyseal injection of a contrast agent was performed. Additionally, standing single-leg stance radiography and dedicated 3-Tesla MRI protocol were employed. The presence of cleft injuries (superior, secondary, combined, atypical) and osteitis pubis was recorded. Symphyseal bone marrow edema (BME) was present in 50 patients, bilaterally in 41 patients and in 28 with an asymmetrical distribution. Comparison of MRI and symphysography was as followed: no clefts: 14 cases (MRI) vs. 24 cases (symphysography), isolated superior cleft sign: 13 vs. 10, isolated secondary cleft sign: 15 vs. 21 cases and combined injuries: 18 vs. 11 cases. In 7 cases a combined cleft sign was observed in MRI but only an isolated secondary cleft sign was visible in symphysography. Anterior pelvic ring instability was observed in 25 patients and was linked to a cleft sign in 23 cases (7 superior cleft sign, 8 secondary cleft signs, 6 combined clefts, 2 atypical cleft injuries). Additional BME could be diagnosed in 18 of those 23. Dedicated 3-Tesla MRI outmatches symphysography for purely diagnostic purposes of cleft injuries. Microtearing at the prepubic aponeurotic complex and the presence of BME is a prerequisite for the development of anterior pelvic ring instability. For diagnostic of symphyseal cleft injuries dedicated 3-T MRI protocols outmatch fluoroscopic symphysography. Prior specific clinical examination is highly beneficial and additional flamingo view x-rays are recommended for assessment of pelvic ring instability in these patients. • Assessment of symphyseal cleft injuries is more accurate by use of dedicated MRI as compared to fluoroscopic symphysography. • Additional fluoroscopy may be important for therapeutic injections. • The presence of cleft injury might be a prerequisite for the development of pelvic ring instability.


Preliminary experience with a large scale vascular registry.
The preliminary study carried out on a voluntary basis, has illustrated the feasibility of a large scale vascular registry serving as a benchmark against which a standard of practice of vascular surgery can be assessed. An initial experience with 165 surgeons active in the clinical practice of surgery (contributing 8,800 major vascular reconstructive cases in a 9 month period) suggests access to an enormous data base of vascular surgery practice against which community standards may be measured.


Spectrum-effect relationship between UPLC fingerprints and anti-lung cancer effect of Panax ginseng.
Lung cancer has the highest mortality rate among the various types of cancer. Panax ginseng (C. A. Mey). is a popular anti-cancer herbal supplement. The quality control of ginseng is crucial to ensure its clinical efficacy. This study aimed to establish new quality control methods for ginseng and to identify its main active components responsible for lung cancer treatment. Ultra-high-performance liquid chromatography (UPLC) was used to establish fingerprints of 18 batches of ginseng. CCK-8 test was performed to evaluate the inhibitory activity of ginseng on Lewis lung cancer (LLC) cells. The spectrum-effect relationship analysis of ginseng was assessed by canonical correlation analysis (CCA) and bioactivity validation. Six common peaks were identified and the variation coefficients were determined. The 18 batches of ginseng inhibited the proliferation of LLC cells to different degrees, showing different half maximal inhibitory concentration (IC50 ) values. Spectrum-effect relationship analysis showed that ginsenoside Ro is the main anti-proliferative constituent of LLC cell. Spectrum-effect relationship is suitable for quality control of ginseng used for lung cancer. It is also effective in discovering the active ingredients related to the clinical efficacy of traditional Chinese medicine.


Disrupted local beta band networks in schizophrenia revealed through graph analysis: A magnetoencephalography study.
Schizophrenia (SZ) is characterized by psychotic symptoms and cognitive impairment, and is hypothesized to be a 'dysconnection' syndrome due to abnormal neural network formation. Although numerous studies have helped elucidate the pathophysiology of SZ, many aspects of the mechanism underlying psychotic symptoms remain unknown. This study used graph theory analysis to evaluate the characteristics of the resting-state network (RSN) in terms of microscale and macroscale indices, and to identify candidates as potential biomarkers of SZ. Specifically, we discriminated topological characteristics in the frequency domain and investigated them in the context of psychotic symptoms in patients with SZ. We performed graph theory analysis of electrophysiological RSN data using magnetoencephalography to compare topological characteristics represented by microscale (degree centrality and clustering coefficient) and macroscale (global efficiency, local efficiency, and small-worldness) indices in 29 patients with SZ and 38 healthy controls. In addition, we investigated the aberrant topological characteristics of the RSN in patients with SZ and their relationship with SZ symptoms. SZ was associated with a decreased clustering coefficient, local efficiency, and small-worldness, especially in the high beta band. In addition, macroscale changes in the low beta band are closely associated with negative symptoms. The local networks of patients with SZ may disintegrate at both the microscale and macroscale levels, mainly in the beta band. Adopting an electrophysiological perspective of SZ as a failure to form local networks in the beta band will provide deeper insights into the pathophysiology of SZ as a 'dysconnection' syndrome.


Short-term starvation stress at young adult stages enhances meiotic activity of germ cells to maintain spermatogenesis in aged male Caenorhabditis elegans.
To survive and reproduce, living organisms must evolve numerous mechanisms to re-adjust their physiology when encountering adverse conditions that subject them to severe stress. We found that short-term starvation (STS) stress in young adult male Caenorhabditis elegans can significantly improve their vitality (relative to nonstressed males) when they are aged. In addition, we found that stress-treated aged males maintained reproductive activity equivalent to young males, whereas nonstressed aged males quickly lost reproductive ability. STS stress can preserve sperm number and quality in aged male worms. Spermatogenesis involves germ cell mitosis and meiosis. We found that germ cell meiotic activity is more sensitive to aging than mitotic activity and is declining rapidly with age. We examined the role of numerous factors important for spermatogenesis on STS-preserved spermatogenesis during aging. Our results show that mutant strains deficient in anaphase-promoting complex/cyclosome (APC/C) function fail to exhibit the STS stress-enhanced spermatogenesis found in wild-type N2 worms, suggesting that the mechanism underlying starvation-induced spermatogenesis involves the APC/C complex, a conserved ubiquitin-protein ligase E3 complex. Furthermore, transgenic expression of FZY-1/CDC-20, a coactivator of APC/C, ameliorated the age-associated decline of meiosis, similar to the hormetic effect of STS.


Acute Kidney Injury in Patients Undergoing Cardiac Transplantation: A Meta-Analysis.
Background: Acute kidney injury (AKI) is a common complication following solid-organ transplantation. However, the epidemiology of AKI and mortality risk of AKI among patients undergoing cardiac transplantation is not uniformly described. We conducted this study to assess the incidence of AKI and mortality risk of AKI in adult patients after cardiac transplantation. Methods: A systematic review of EMBASE, MEDLINE, and Cochrane Databases was performed until June 2019 to identify studies evaluating the incidence of AKI (by standard AKI definitions), AKI requiring renal replacement therapy (RRT), and mortality risk of AKI in patients undergoing cardiac transplantation. Pooled AKI incidence and mortality risk from the included studies were consolidated by random-effects model. The protocol for this study is registered with PROSPERO (no. CRD42019134577). Results: 27 cohort studies with 137,201 patients undergoing cardiac transplantation were identified. Pooled estimated incidence of AKI and AKI requiring RRT was 47.1% (95% CI: 37.6-56.7%) and 11.8% (95% CI: 7.2-18.8%), respectively. The pooled ORs of hospital mortality and/or 90-day mortality among patients undergoing cardiac transplantation with AKI and AKI requiring RRT were 3.46 (95% CI, 2.40-4.97) and 13.05 (95% CI, 6.89-24.70), respectively. The pooled ORs of 1-year mortality among patients with AKI and AKI requiring RRT were 2.26 (95% CI, 1.56-3.26) and 3.89 (95% CI, 2.49-6.08), respectively. Conclusion: Among patients undergoing cardiac transplantation, the incidence of AKI and severe AKI requiring RRT are 47.1% and 11.8%, respectively. AKI post cardiac transplantation is associated with reduced short term and 1-year patient survival.


The molecular landscape of progressive familial intrahepatic cholestasis in Turkey: Defining the molecular profiles and expanding the variant spectrum.
Progressive familial intrahepatic cholestasis (PFIC) is a rare genetically heterogeneous group of autosomal recessive liver disorders that manifests as intrahepatic cholestasis during the neonatal period. ATP8B1, ABCB11, and ABCB4 genes are responsible for PFIC type 1, PFIC type 2, and PFIC type 3, respectively. To determine the underlying molecular etiology of PFIC, 80 patients from 77 families were investigated. The molecular genetic diagnosis was applied by using next-generation sequencing (NGS) and revealed 29 different variants from 32 patients. In this study, we evaluated these variants according to mechanisms, clinical sub-groups, and genotype-phenotype correlation.


Septal influences on the activity of hippocampal neurones during sleep.
Septal influences on CA1 and DG neurones were studied in sleeping cats before and after septal lesions suppressing the theta rhythm. Septal influences tonically gauge the activity level of a discrete group of CA1 and DG neurones, regardless of sleep stages. The observed splitting of each CA1 and DG population into two groups of units showing opposite changes in firing rate from SS to DS may be related to extraseptal inputs.


Cognitive Motor Dissociation: Gap Analysis and Future Directions.
Patients with disorders of consciousness who are behaviorally unresponsive may demonstrate volitional brain responses to motor imagery or motor commands detectable on functional magnetic resonance imaging or electroencephalography. This state of cognitive motor dissociation (CMD) may have prognostic significance. The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of monthly online meetings between September 2021 and April 2023 to examine the science of CMD and identify key knowledge gaps and unmet needs. The group identified major knowledge gaps in CMD research: (1) lack of information about patient experiences and caregiver accounts of CMD, (2) limited epidemiological data on CMD, (3) uncertainty about underlying mechanisms of CMD, (4) methodological variability that limits testing of CMD as a biomarker for prognostication and treatment trials, (5) educational gaps for health care personnel about the incidence and potential prognostic relevance of CMD, and (6) challenges related to identification of patients with CMD who may be able to communicate using brain-computer interfaces. To improve the management of patients with disorders of consciousness, research efforts should address these mechanistic, epidemiological, bioengineering, and educational gaps to enable large-scale implementation of CMD assessment in clinical practice.


Economic evaluation comparing intraoperative cone beam CT-based navigation and conventional fluoroscopy for the placement of spinal pedicle screws: a patient-level data cost-effectiveness analysis.
Pedicle screws are routinely used in contemporary spinal surgery. Screw misplacement may be asymptomatic but is also correlated with potential adverse events. Computer-assisted surgery (CAS) has been associated with improved screw placement accuracy rates. However, this technology has substantial acquisition and maintenance costs. Despite its increasing usage, no rigorous full economic evaluation comparing this technology to current standard of care has been reported. Medical costs are exploding in an unsustainable way. Health economic theory requires that medical equipment costs be compared with expected benefits. To answer this question for computer-assisted spinal surgery, we present an economic evaluation looking specifically at symptomatic misplaced screws leading to reoperation secondary to neurologic deficits or biomechanical concerns. The study design was an observational case-control study from prospectively collected data of consecutive patients treated with the aid of CAS (treatment group) compared with a matched historical cohort of patients treated with conventional fluoroscopy (control group). The patient sample consisted of consecutive patients treated surgically at a quaternary academic center. The primary effectiveness measure studied was the number of reoperations for misplaced screws within 1 year of the index surgery. Secondary outcome measures included were total adverse event rate and postoperative computed tomography usage for pedicle screw examination. A patient-level data cost-effectiveness analysis from the hospital perspective was conducted to determine the value of a navigation system coupled with intraoperative 3-D imaging (O-arm Imaging and the StealthStation S7 Navigation Systems, Medtronic, Louisville, CO, USA) in adult spinal surgery. The capital costs for both alternatives were reported as equivalent annual costs based on the annuitization of capital expenditures method using a 3% discount rate and a 7-year amortization period. Annual maintenance costs were also added. Finally, reoperation costs using a micro-costing approach were calculated for both groups. An incremental cost-effectiveness ratio was calculated and reported as cost per reoperation avoided. Based on reoperation costs in Canada and in the United States, a minimal caseload was calculated for the more expensive alternative to be cost saving. Sensitivity analyses were also conducted. A total of 5,132 pedicle screws were inserted in 502 patients during the study period: 2,682 screws in 253 patients in the treatment group and 2,450 screws in 249 patients in the control group. Overall accuracy rates were 95.2% for the treatment group and 86.9% for the control group. Within 1 year post treatment, two patients (0.8%) required a revision surgery in the treatment group compared with 15 patients (6%) in the control group. An incremental cost-effectiveness ratio of $15,961 per reoperation avoided was calculated for the CAS group. Based on a reoperation cost of $12,618, this new technology becomes cost saving for centers performing more than 254 instrumented spinal procedures per year. Computer-assisted spinal surgery has the potential to reduce reoperation rates and thus to have serious cost-effectiveness and policy implications. High acquisition and maintenance costs of this technology can be offset by equally high reoperation costs. Our cost-effectiveness analysis showed that for high-volume centers with a similar case complexity to the studied population, this technology is economically justified.


Emergency department preparedness trainings in New York State: a needs assessment.
An assessment of preparedness training of emergency department (ED) staff in many upstate New York hospitals was carried out using an institutional review board-approved questionnaire. Several aspects of training such as content, quality, quantity, methodology, and skills obtained as a result of trainings were examined. The results suggest that respondents in upstate New York would like to see more training on specific topics of information (chemical and radiological concerns) and the utilization of new technologies, such as on-line courses, to optimize time commitments.