In vivo comparison of dl-sotalol-induced electrocardiographic responses among halothane anesthesia, isoflurane anesthesia with nitrous oxide, and conscious state.
We compared dl-sotalol-induced electrocardiographic responses in intact dogs using a repeated-measures design among 1% halothane anesthesia, 1.5% isoflurane anesthesia with nitrous oxide (N2O), and conscious state to clarify influences of the anesthetics (n = 4). Basal PR interval was longer in halothane than either in isoflurane with N2O or in conscious state, reflecting sympathetic nerve suppression for the atrioventricular node by halothane. Both anesthetics exhibited longer basal QRS width than conscious state, suggesting their ventricular INa inhibition. Also, both anesthetics showed longer basal QT interval, QTcF and Tpeak-Tend than conscious state, indicating their ventricular IKr inhibition. Meanwhile, dl-sotalol prolonged PR interval similarly in isoflurane with N2O and in conscious state, which was less great in halothane, suggesting further sympathetic nerve suppression for the atrioventricular node might be limited in halothane. dl-Sotalol prolonged QT interval and QTcF >3 times greater in either of the anesthetics than in conscious state; moreover, dl-sotalol prolonged Tpeak-Tend similarly in both anesthetics, but hardly altered it in conscious state; indicating isoflurane with N2O as well as halothane may have reduced the repolarization reserve to increase the sensitivity of ventricle toward IKr suppression. Thus, isoflurane with nitrous oxide could be useful for in vivo IKr assay like halothane.


Health Care and Adoption Service Experiences of People Who Placed Children for Adoption During Adolescence: A Qualitative Study.
To understand the perspectives of people who placed children for adoption during adolescence DESIGN: We conducted qualitative interviews with adults who placed children for adoption during adolescence. We recruited participants through social media and two adoption-related organizations. We audio-recorded and transcribed interviews. Using thematic analysis, 2 investigators coded the transcripts and identified themes. Telephone interviews PARTICIPANTS: Adults ages 18-35 years old who placed children for adoption before they were 20 years old INTERVENTIONS: Semi-structured telephone interviews MAIN OUTCOME MEASURES: Qualitative data RESULTS: We conducted interviews with 18 individuals (median age of 32 years; range 21-35 years). The median age at pregnancy was 18 years (range 13-19 years). Seventeen participants identified as female and one as nonbinary. Themes included the following: (1) Negative experiences with counseling included limited empowerment to make choices about pregnancy or adoption options; (2) negative experiences with counseling included limited information about practical or financial support for pregnant adolescents; (3) negative experiences with the health care system included insensitivity or lack of awareness of the adoption plan at delivery; (4) positive experiences with counseling included comprehensive unbiased options counseling and adoption counseling emphasizing birth parent choice in openness and family placement; (5) positive experiences included longitudinal emotional support during pregnancy, particularly in ways that normalized adoption placement; and (6) participants desired therapy and/or psychological support following adoption placement. Individuals who chose adoption after adolescent pregnancy described positive and negative encounters with health care and adoption professionals that could serve as targets to improve the overall care experience for this population.


Effectiveness of the integration of a palliative care team in the follow-up of patients with advanced chronic obstructive pulmonary disease: The home obstructive lung disease study.
Access to palliative care for patients with end-stage chronic obstructive pulmonary disease (COPD) is still very poor. Evaluate our palliative care program for patients with advanced COPD by assessing whether the referral criteria for advanced COPD patients were adequate in identifying patients in end-of-life care and determine the results of the palliative care team's intervention METHODS: This was a prospective observational study of patients admitted to a multidisciplinary unit for advanced COPD. Data on sociodemographic variables, survival, symptomatology, quality of life, ACP, and health resource utilization were analyzed. Eighty-three patients were included in this study. By the end of the follow-up period, 69 (83%) patients had died, mainly due to respiratory failure (96%). The median duration of survival from the start of follow-up was 4.27 months (95% confidence interval, 1.97-16.07). Most patients (94%) had a dyspnea level of 4. Sixty (72%) patients required opioids for dyspnea control. There were no significant differences in the quality of life of the patients during follow-up. Thirty (43%) patients died at home, 26 (38%) in a palliative care unit, and 13 (19%) in an acute care hospital. ACP was performed for 50 (72%) patients. Forty (57%) patients required palliative sedation during follow-up. Dyspnea was the reason for sedation in 34 (85%) patients. Hospital admissions and emergency room visits decreased significantly (p = 0.01) during follow-up. Our integrated model allows for adequate selection of patients, facilitates symptom control and ACP, reduces resource utilization, and favors death at home.


peri-Acenoacene Ribbons with Zigzag BN-Doped Peripheries.
Here, we report the synthesis of BN-doped graphenoid nanoribbons, in which peripheral carbon atoms at the zigzag edges have been selectively replaced by boron and nitrogen atoms as BN and NBN motifs. This includes high-yielding ring closure key steps that, through N-directed borylation reaction using solely BBr3, allow the planarization of meta-oligoarylenyl precursors, through the formation of B-N and B-C bonds, to give ter-, quater-, quinque-, and sexi-arylenyl nanoribbons. X-ray single-crystal diffraction studies confirmed the formation of the BN and NBN motifs and the zigzag-edged topology of the regularly doped ribbons. Steady-state absorption and emission investigations at room temperature showed a systematic bathochromic shift of the UV-vis absorption and emission envelopes upon elongation of the oligoarylenyl backbone, with the nanoribbon emission featuring a TADF component. All derivatives displayed phosphorescence at 77 K. Electrochemical studies showed that the π-extension of the peri-acenoacene framework provokes a lowering of the first oxidative event (from 0.83 to 0.40 V), making these nanoribbons optimal candidates to engineer p-type organic semiconductors.


Muscle-derived autologous mitochondrial transplantation: A novel strategy for treating cerebral ischemic injury.
The available evidence showed that mitochondrial transfer by releasing the extracellular vesicles containing mitochondria from astrocytes to neurons exerted a neuroprotective effect after stroke. Whether extracellular mitochondrial replenishment could rescue the tissues from cerebral ischemic injury still needs to be explored completely. It was hypothesized that the augmentation of mitochondrial damage after cerebral ischemia could be resolved by timely replenishment of exogenous mitochondria. A stroke model of middle cerebral artery occlusion (MCAO) was used in this study to verify this hypothesis. This study found that the number of extracellular mitochondria increased in rat cerebrospinal fluid after MCAO, and a higher proportion of mitochondria were associated with good neurological outcomes. Following 90-min ischemia, autologously derived mitochondria (isolated from autologous pectoralis major) or vehicle alone was infused directly into the lateral ventricles, and the rats were allowed to recover for 4 weeks. A plenty of infused mitochondria were found to be distributed in the boundary and ischemic penumbra areas. Furthermore, the transplantation of mitochondria reduced cellular oxidative stress and apoptosis, attenuated reactive astrogliosis, and promoted neurogenesis after stroke. Moreover, the transplantation of mitochondria decreased brain infarct volume and reversed neurological deficits. The findings suggested that the delivery of mitochondria through the lateral ventricles resulted in their widespread distribution throughout the brain and exerted a neuroprotective effect after ischemia-reperfusion injury.


Transcription and division inhibitors in the medium of stationary phase cultures of the slime mold Dictyostelium discoideum.
When cell-free medium of a stationary phase culture is added to an exponentially multiplying culture, it blocks further cell division and depresses the level of nuclear transcription. Furthermore, when cell-free medium of a stationary phase culture is added directly to an in vitro transcription system containing nuclei isolated from exponentially multiplying amebae, it completely inhibits "late" incorporation (20-60 min reaction time), which is predominantly alpha-amanitin resistant (ribosomal-like). The stationary phase medium however, affects neither "early" alpha-amanitin resistant incorporation (0-20 min reaction time) nor alpha-amanitin sensitive incorporation. Inhibition of late in vitro transcription is not due to a nucleotidase, nor is it due to changes in the pH, ionic strength, or osmolarity of the reaction mixture.


Risk factors of Coxiella burnetii (Q fever) seropositivity in veterinary medicine students.
Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors. A cross-sectional study with questionnaire and blood sample collection was performed among all veterinary medicine students studying in The Netherlands in 2006. Serum samples (n = 674), representative of all study years and study directions, were analyzed for C. burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1:32 and above. Of the veterinary medicine students 126 (18.7%) had IgG antibodies against C. burnetii. Seropositivity associated risk factors identified were the study direction 'farm animals' (Odds Ratio (OR) 3.27 [95% CI 2.14-5.02]), advanced year of study (OR year 6: 2.31 [1.22-4.39] OR year 3-5 1.83 [1.07-3.10]) having had a zoonosis during the study (OR 1.74 [1.07-2.82]) and ever lived on a ruminant farm (OR 2.73 [1.59-4.67]). Stratified analysis revealed study direction 'farm animals' to be a study-related risk factor apart from ever living on a farm. In addition we identified a clear dose-response relation for the number of years lived on a farm with C. burnetii seropositivity. C. burnetii seroprevalence is considerable among veterinary medicine students and study related risk factors were identified. This indicates Q fever as an occupational risk for veterinary medicine students.


New understandings on folliculogenesis/oogenesis regulation in mouse as revealed by conditional knockout.
In comparison to conventional knockout technology and in vitro research methods, conditional gene knockout has remarkable advantages. In the past decade, especially during the past five years, conditional knockout approaches have been used to study the regulation of folliculogenesis, follicle growth, oocyte maturation and other major reproductive events. In this review, we summarize the recent findings about folliculogenesis/oogenesis regulation, including the functions of four signaling cascades or glycoprotein domains that have been extensively studied by conditional gene deletion. Several other still fragmented areas of related work are introduced which are awaiting clarification. We have also discussed the future potential of this technology in clarifying gene functions in reproductive biology.


Neoplasia of the respiratory tract.
Tumors of the equine respiratory tract occur infrequently. An accurate diagnosis of neoplasia of the respiratory tract is critical because the prognosis is usually grave. The clinical signs and diagnostic procedures are discussed for tumors of the nasal and paranasal sinuses, nasopharynx/larynx, guttural pouch and thorax including lung, pleura, and thymus.


On being understood: clarity and jargon in radiation protection.
While much of the language used to express the concepts of radiation protection works effectively, there are many ill-chosen names and phrases and much jargon that permeate our professional speech and writing. From the oxymoron "internal exposure" to the "snarl word" "decay," there is much room for improvement. This essay identifies many of the problems and suggests solutions. We examine the kinds of confusions that can result from using familiar words with unfamiliar meanings and the need for neology. We offer insights into specific and unambiguous naming of physical quantities and explore the seemingly unlimited kinds of "dose." We disaggregate exposure from irradiation following intakes, and unmask units like "gram rad per microcurie hour." We call for a definition of radiation weighting factor that doesn't result in a violation of the law of conservation of energy. We examine the subtleties of distinguishing between radiation and radioactive materials. Some words, such as "exposure," have multiple meanings, while at other times there are different words or phrases with the same meaning, such as "critical level" and "decision level" or "detection level" and "minimum detectable amount." Sometimes phrases are used whose meaning is unclear or not agreed upon, such as "lower limit of detection." Sometimes there are words that are simply not apt, such as "disintegration" applied to the emission of a subatomic particle from a nucleus.


Analgesia produced by immobilization stress and an enkephalinase inhibitor in amphibians.
The role of endogenous opioids in modulating pain transmission in amphibians was examined by two methods known to activate endogenous opioids in mammals. Analgesia was assessed using the acetic acid test in the Northern grass frog, Rana pipiens. One or 2 h of immobilization produced a significant analgesia lasting for at least 90 min. Systemic, but not spinal, administration of naloxone before immobilization prevented the analgesic effects seen in saline-pretreated controls. Spinal administration of the enkephalinase inhibitor, thiorphan, but not bestatin (both at 100 nmol/frog), produced significant analgesia. The analgesic effect of thiorphan was blocked by coadministration of intraspinal naloxone. These data are the first to suggest a role for endogenous opioid modulation of noxious stimuli in lower vertebrates by examination of stress-induced analgesia and the action of agents that inhibit enkephalin degradation.


Determination of EGFR-overexpressing tumor cells by magnetic gold-decorated graphene oxide nanocomposites based impedance sensor.
This work developed an electrochemical impedance spectroscopy (EIS) sensor for detection of EGFR (epidermal growth factor receptor)-overexpressing tumor cell and preliminary estimation of EGFR expression. Here, EGFR antibodies as the specific antibodies for cancer cells were conjugated on magnetic gold-decorated graphene oxide nanocomposites, which were used to capture the EGFR-overexpressing tumor cells. The magnetically responsive tumor cells were enriched and immobilized on a magnetic glassy carbon electrode (mGCE) surface, leading to increased electron-transfer resistance (Ret) utilized for determination of cells and preliminary evaluation of EGFR expression level. This strategy enables the enrichment, fixation and detection of tumor cells to be accomplished in a facile way. An excellent linearity in the range of 2.0 × 102 - 3.0 × 105 cell mL-1 with the detection limit of 152 cell mL-1 for MDA-MB-231 cells was obtained. Investigation on the expression levels of EGFR on various types of cells was conducted. MDA-MB-231 cells showed a distinctly higher EGFR expression, compared with MHCC97-L and L02 cells, providing the possibility for the EGFR-targeted therapy of the tumors. It is expected that the proposed sensor has the potential to be applied for cancer monitoring.


Magnetic resonance imaging of intracranial hemorrhage.
The appearance and evolution of intracranial hemorrhage as detected by magnetic resonance (MR) imaging is complex. This article outlines the underlying physiology of hemorrhagic masses in order to explain their complex appearance. The MR appearance of intraparenchymal (benign and neoplastic) and extraparenchymal intracranial hemorrhage is described.


Spanish translations of Miranda warnings and the totality of the circumstances.
Spanish-translated Miranda warnings are administered annually to thousands of Hispanic custodial suspects. In examining 121 Spanish translations and their English counterparts from 33 states, the lengths of Miranda warnings were generally comparable but marked differences were observed in the reading levels for individual Miranda components. The adequacy of Miranda translations varies markedly from minor variations to substantive errors. The most serious problems involved the entire omission of Miranda components; several omissions were observed in the Spanish translations for even the basic rights to silence and counsel. More commonly, Miranda discrepancies involved dissimilar content with a substantial trend toward more information in English than Spanish versions. Findings related to the Miranda translations, different word lengths, and varied reading levels are discussed using the totality of circumstances as its framework.


Outcomes of Primary and Secondary Carotid Artery Stenting.
Little is known of the excess risk attributable to secondary carotid angioplasty and stenting (CAS). This study evaluates outcomes of redo-CAS and CAS after prior ipsilateral carotid endarterectomy (CASAPICEA) relative to primary-CAS. We studied all patients in the Vascular Quality Initiative, who underwent primary-CAS, CASAPICEA, or redo-CAS (2003-2016). Kaplan-Meier, multivariable logistic and Cox regression analyses were used to evaluate outcomes within 30 days and up to 1 year and identify their predictors. There were 11 742 CAS procedures performed: 8519 (72%) primary-, 2645 (23%) CASAPICEA, and 578 (5%) redo-CAS. Comparing primary-CAS versus CASAPICEA versus redo-CAS, 30-day stroke/death was 2.5% versus 2.0% versus 1.3% for asymptomatic patients (P=0.23) and 5.2% versus 2.6% versus 5.0% for symptomatic patients (P=0.003). CASAPICEA was associated with significantly lower 30-day stroke/death (odds ratio: 0.60; 95% confidence interval: 0.37-0.98; P=0.04) compared with primary-CAS among symptomatic patients. The odds of bradycardia were lower following CASAPICEA (odds ratio: 0.32; 95% confidence interval: 0.26-0.39; P<0.001) and redo-CAS (odds ratio: 0.55; 95% confidence interval: 0.39-0.78; P=0.001) compared with primary-CAS. Similarly, the odds of hypotension were significantly lower in both groups compared with primary-CAS (CASAPICEA: 0.41 [0.35-0.48], P<0.001; redo-CAS: 0.66 [0.50-0.86] P=0.003). There were no significant differences in the hazards of stroke/death at 1 year for CASAPICEA and redo-CAS compared with primary-CAS. CASAPICEA is associated with significantly lower odds of periprocedural stroke/death compared with primary-CAS among symptomatic patients. CASAPICEA and redo-CAS are associated with significantly lower odds of periprocedural hypotension and bradycardia but higher odds of hypertension compared with primary-CAS.


Reactivating addiction-related memories under propranolol to reduce craving: A pilot randomized controlled trial.
The reconsolidation blocker propranolol abolishes alcohol and drug-seeking behavior in rodents and attenuates conditioned emotional responses to drug-cues in humans in experimental settings. This suggests a role for its use in the treatment of substance dependence. In this translational pilot study, we explored the feasibility and efficacy of this procedure as an adjunct treatment for addiction. We hypothesized that guided addiction-related memory reactivation under propranolol would significantly attenuate tonic craving, a central element in relapse following addiction treatment. Seventeen treatment-seeking adults diagnosed with substance dependence were randomized to receive double-blind propranolol (n = 9) or placebo (n = 8) on six occasions prior to reading a personalized script detailing a drug-using experience. The primary outcome measure was self-reported craving intensity. After controlling for baseline craving scores, intent-to-treat analysis revealed a time by group interaction, F(1, 14) = 5.68, p = .03, η(2) = 0.29; craving was reduced in the propranolol-treated group (Cohen's d = 1.40, p < .05) but not in the placebo group (d = 0.06, n.s.). The usual limitations related to small sample size and the lack of a follow-up apply here. Drug-related memory reactivation under propranolol can subsequently reduce craving among substance-dependent individuals. Considering the relapse rate among individuals treated for substance dependence, our study highlights the feasibility of, and need for, more comprehensive trials of this treatment approach.


Depiction of the forces participating in the 2-O-sulfo-alpha-L-iduronic acid conformational preference in heparin sequences in aqueous solutions.
2-O-Sulfo-alpha-l-iduronic acid (IdoA2S) is one of the main components of heparin, an anticoagulant and antithrombotic polysaccharide able to potentiate the inhibitory effect of antithrombin over plasma serine proteases. This monosaccharide unit adopts an equilibrium between chair (1C4) and skew-boat (2SO) forms as a function of heparin sequence size and composition. Although the prevalence of the 1C4 chair conformation in monosaccharides is understood, the reasons for the increase in 2SO contribution in the whole polysaccharide chain are still uncertain. In this context, 0.2 mus molecular dynamics simulations of IdoA2S-containing oligosaccharides indicated that stabilization due to intramolecular hydrogen bonds around IdoA2S is highly correlated (p0.001) with the expected conformational equilibrium for this residue in solution. This behavior explains the known effect of different heparin compositions, at the monosaccharide level, on IdoA2S conformation in biological solutions.


Green synthesis of ZnO, MgO and SiO2 nanoparticles and its effect on irrigation water, soil properties, and Origanum majorana productivity.
The synthesis of different metal oxide nanoparticles (NPs) (e.g., ZnO, MgO and SiO2) using green methods is a promising alternative to traditional chemical methods. In this work, ZnO, MgO, and SiO2 NPs were prepared using lemon peel extract. The synthesized NPs were characterized using Fourier transform infrared spectroscopy, UV-Visible spectroscopy, X-ray diffraction, and transmission electron microscopy. Also, the effects of the green synthesis of different NPs on the irrigation water quality, the availability of some heavy metals in soil and plants, and the productivity of Origanum majorana (marjoram) were studied in detail. The obtained results showed that the addition of the NPs resulted in noticeable variations in the removal percentages of Cu2+ and Fe3+ from aqueous solutions. The maximum values obtained for the adsorption of Cu(II) on ZnO, MgO, and SiO2 NPs within the pH values of 3-5 were 89.9%, 83.3%, and 68.36%, respectively. Meanwhile, the maximum adsorption values of Fe(III) at pH 3.3 were 82%, 80%, and 65% for ZnO, MgO, and SiO2 NPs, respectively. Clearly, the application of the NPs effectively reduced the available Cu2+ in the studied soil samples in the following order: Zn2 > Zn1 > Mg2 > Si2 > Mg1 > Si1 > C (control). The highest values of available Cu2+ were observed in the control treatment, whereas the lowest values were obtained when Zn2 was added. The same tendencies were observed with substantial concentrations of Fe. The addition of NPs to the soil samples positively affected the plants' Cu2+ uptake. The effects of NPs and the additions of Cu2+ and Fe3+ on the availability of nitrogen, phosphorus, and potassium (NPK) in the soil system were very completed and osculated from one treatment to another. The same tendencies were observed with the total concentration of NPK in plants.


Recurrent autonomic and sensory neuropathy in a patient with anti-ganglionic acetylcholine receptor antibodies.
We report a case of recurrent neuropathy with predominant autonomic and sensory involvement whose serum was positive for anti-ganglionic acetylcholine receptor (anti-gAChR) antibodies, a diagnostic marker of autoimmune autonomic ganglionopathy. An 11-year-old girl complained of numbness and limb pain after gastroenteritis. Although hyperalgesia and autonomic dysfunctions, such as orthostatic intolerance and gastrointestinal dysmotility subsequently developed, these symptoms faded after a few days. Similar sensory and autonomic impairments recurred three times within 12 months after the first episode. The sensory and autonomic symptoms were rapidly ameliorated by the administration of intravenous immunoglobulin (IVIg) at the second and third relapse; however, the symptoms persisted even after the administration of IVIg at the fourth relapse. The residual symptoms disappeared after methylprednisolone pulse therapy. The patient's serum was found to be positive for anti-gAChR antibodies at the second relapse, and was negative after methylprednisolone pulse therapy. Further studies are needed to clarify the efficacy of treatment and the nosological position in the spectrum of neuropathies that are associated with autonomic and sensory impairments.


Developmental origin of segmental differences in the leech ectoderm: survival and differentiation of the distal tubule cell is determined by the host segment.
The body plan of the adult leech is metameric, with each hemisegmental complement of ectodermal and mesodermal tissues being produced from a set of seven serially repeated embryonic blast cells. Previous studies have shown that homologous o blast cells give rise to an almost identical complement of descendant cells in each of the 21 abdominal segments, but that one o blast cell derivative--the distalmost cell of the nephridial tubule--is only present in 15 abdominal segments in the mature leech. Here we show that all o blast cells generate a presumptive distal tubule cell and that this cell migrates to its normal position in all abdominal segments. However, in segments which normally do not contain the mesodermal portion of the nephridium, the distal tubule cell dies before undergoing its terminal morphological differentiation. To ascertain whether the fate of the distal tubule cell is determined by its lineage history or by the segmental environment into which it is born, we utilized a previously described procedure for altering the segmental register between different embryonic cell lines. This procedure allowed us to effectively transplant o blast cells into more posterior segments prior to the cell divisions which generate their descendant clones. The results indicate that the survival or death of the distal tubule cell is determined by the identity of the host segment and that a given distal tubule cell could be effectively murdered or rescued by slipping its blast cell precursor into an appropriate segment. These findings suggest that the segment-specific pattern of distal tubule cell survival is not inherent to the O cell line, but arises from interactions with surrounding tissues.


[Effect of different shape and material of intraocular lens on posterior capsule opacification].
In this paper we compare 4 groups of intraocular lenses: PMMA, silicone, hydrogel, acrylic and their influence on posterior capsule opacification is discussed. The possible clinical consequences of different shape in optic part of intraocular lens is also described. This article contains also a short presentation of posterior capsule opacification mechanism and intraocular lens materials biocompatibility in in-vivo and in-vitro experiments.


Genetic code preferentially conserves long-range interactions among the amino acids.
The physical properties of amino acids were investigated in order to evaluate their possible relationship to the assignment of codons for amino acids in the genetic code. A comparison of the interconversion probability between amino acids and the distances between the amino acids for individual physical properties revealed a striking hierarchy among the physical properties. Surprisingly, it is the long-range/solvent interactions and not the short-range/stereochemical properties which are preferentially conserved in the genetic code.


Digging into the HLA pockets: A new association with acute leukaemias.
Acute leukaemias represent a highly heterogeneous group of clonal proliferations of myeloid or lymphoid blasts. In the last decade, the contribution of immunogenetics to cancer biology has elicited a renewed interest in the structures of immune adaptive responses, due to the growing body of evidence concerning their involvement into disease pathogenesis and treatment. The report by Boukouaci and colleagues suggests new associations between patterns of distribution of specific human leukocyte antigen motifs and leukaemogenesis. Commentary on Boukouaci Wahid et al. Comparative analysis of the variability of the HLA peptide-binding pockets in patients with acute leukemias" Br J Haematol 2023;200:203-215.


Vascularization of three-dimensional engineered tissues for regenerative medicine applications.
Engineering of three-dimensional (3D) tissues is a promising approach for restoring diseased or dysfunctional myocardium with a functional replacement. However, a major bottleneck in this field is the lack of efficient vascularization strategies, because tissue constructs produced in vitro require a constant flow of oxygen and nutrients to maintain viability and functionality. Compared to angiogenic cell therapy and growth factor treatment, bioengineering approaches such as spatial micropatterning, integration of sacrificial materials, tissue decellularization, and 3D bioprinting enable the generation of more precisely controllable neovessel formation. In this review, we summarize the state-of-the-art approaches to develop 3D tissue engineered constructs with vasculature, and demonstrate how some of these techniques have been applied towards regenerative medicine for treatment of heart failure. Tissue engineering is a promising approach to replace or restore dysfunctional tissues/organs, but a major bottleneck in realizing its potential is the challenge of creating scalable 3D tissues. Since most 3D engineered tissues require a constant supply of nutrients, it is necessary to integrate functional vasculature within the tissues in order to facilitate the transport of nutrients. To address these needs, researchers are employing biomaterial engineering and design strategies to foster vessel formation within 3D tissues. This review highlights the state-of-the-art bioengineering tools and technologies to create vascularized 3D tissues for clinical applications in regenerative medicine, highlighting the application of these technologies to engineer vascularized cardiac patches for treatment of heart failure.


Interleukin 2 induces T cell-dependent IgM production in human B cells.
Conditioned medium, obtained from mononuclear cells after activation with concanavalin A and phorbol myristate, strongly stimulated the in vitro production of IgM by human mononuclear cells. Partial purification by gel filtration showed that this activity co-eluted with interleukin 2 (IL 2). Via removal by adsorption and further purification by chromatofocusing techniques, it was demonstrated that the factor in this conditioned medium, responsible for the IgM production, was in fact IL 2. Experiments with purified IL 2 from the human IL 2-producing Jurkat cell line as well as recombinant IL 2 confirmed its capacity to induce IgM production. In the absence of T cells, IL 2 could not activate Ig synthesis, suggesting an indirect effect of IL 2 in the induction of the helper signals for B cells. Evidence is presented that partially purified conditioned medium contained another factor, distinct from IL 2, with the capacity to differentiate human B lymphocytes in the absence of T cells into IgM-producing cells.


Shellfish contamination with marine biotoxins in Portugal and spring tides: a dangerous health coincidence.
Bivalve molluscs can acquire marine biotoxins by filter-feeding upon certain toxin-producing microalgae. The two most common syndromes observed in temperate coastal waters have been diarrhetic shellfish poisoning (DSP) and paralytic shellfish poisoning (PSP). While DSP is a non-fatal gastrointestinal syndrome, PSP is a neurological syndrome which can lead to death by respiratory paralysis in high intoxication scenarios. In Portugal, the presence of both DSP and PSP toxins leads to recurrent seasonal bans of bivalve harvesting. On a few occasions, the bans were not placed in time, not properly disseminated to the public or were disregarded by recreational harvesters. Several cases of poisonings have been studied in collaboration between health authorities and the laboratory in charge of the biotoxin monitoring programme. Some of the outbreaks have even called the attention of the local media. In several of these recorded cases, a common trait has emerged throughout the years: bivalve harvest had often been done during very low tides attributed to either new or full moons. These tides expose intertidal bivalves more widely, increase harvesting time, and allow picking of larger-sized specimens. In some occasions, the consumers were extremely unfortunate because a noxious coincidence had occurred: larger-sized specimens were available but had attained the highest toxin content of the toxic season. This review alerts that despite costly monitoring programmes have been perfected through the years, human poisonings still take place due to the rapid increase in toxin levels and/or disrespect of harvest bans.


Tyrosine kinase inhibitors suppress prostaglandin F2alpha-induced phosphoinositide hydrolysis, Ca2+ elevation and contraction in iris sphincter smooth muscle.
We investigated the effects of the protein tyrosine kinase inhibitors, genistein, tyrphostin 47, and herbimycin on prostaglandin F2alpha- and carbachol-induced inositol-1,4,5-trisphosphate (IP3) production, [Ca2+]i mobilization and contraction in cat iris sphincter smooth muscle. Prostaglandin F2alpha and carbachol induced contraction in a concentration-dependent manner with EC50 values of 0.92 x 10(-9) and 1.75 x 10(-8) M, respectively. The protein tyrosine kinase inhibitors blocked the stimulatory effects of prostaglandin F2alpha, but not those evoked by carbachol, on IP3 accumulation, [Ca2+]i mobilization and contraction, suggesting involvement of protein tyrosine kinase activity in the physiological actions of the prostaglandin. Daidzein and tyrphostin A, inactive negative control compounds for genistein and tyrphostin 47, respectively, were without effect. Latanoprost, a prostaglandin F2alpha analog used as an antiglaucoma drug, induced contraction and this effect was blocked by genistein. Genistein (10 microM) markedly reduced (by 67%) prostaglandin F2alpha-stimulated increase in [Ca2+]i but had little effect on that of carbachol in cat iris sphincter smooth muscle cells. Vanadate, a potent inhibitor of protein tyrosine phosphatase, induced a slow gradual muscle contraction in a concentration-dependent manner with an EC50 of 82 microM and increased IP3 generation in a concentration-dependent manner with an EC50 of 90 microM. The effects of vanadate were abolished by genistein (10 microM). Wortmannin, a myosin light chain kinase inhibitor, reduced prostaglandin F2alpha- and carbachol-induced contraction, suggesting that the involvement of protein tyrosine kinase activity may lie upstream of the increases in [Ca2+]i evoked by prostaglandin F2alpha. Further studies aimed at elucidating the role of protein tyrosine kinase activity in the coupling mechanism between prostaglandin F2alpha receptor activation and increases in intracellular Ca2+ mobilization and identifying the tyrosine-phosphorylated substrates will provide important information about the role of protein tyrosine kinase in the mechanism of smooth muscle contraction, as well as about the mechanism of the intraocular pressure lowering effect of the prostaglandin in glaucoma patients.


Nanopharmaceutical approach using pelargonidin towards enhancement of efficacy for prevention of alloxan-induced DNA damage in L6 cells via activation of PARP and p53.
Alloxan is an environmental food contaminant that causes DNA damage in living cells and induces hyperglycemia. Pelargonidin (PG), an active ingredient found in extract of various fruits and vegetables, has been nanoencapsulated (NPG) with poly-lactide-co-glycolide (PLGA) and tested for efficacy in prevention of alloxan (ALX)-induced DNA damage in L6 cells in vitro. Glucose uptake, reactive oxygen species (ROS) generation, glucose transporter 4, glucokinase levels and mechanism of activation of DNA repair proteins (PARP and p53) have been studied in ALX-induced L6 cells. Drug-DNA interaction has been analyzed using calf thymus DNA as target through circular dichroism and melting temperature profile. NPGs were physico-chemically characterized by standard protocols using dynamic light scattering and transmission electron microscopy. Pre-treatment with both PG and/or NPG was effective in reducing ALX-induced oxidative stress and showed favourable effects for protection against DNA damage by activating DNA repair cascades. Results suggested ∼10-fold increase in efficacy of NPG than PG in prevention of alloxan-induced oxidative stress and DNA damage.


Chromosomal studies in Callicebus donacophilus pallescens, with classic and molecular cytogenetic approaches: multicolour FISH using human and Saguinus oedipus painting probes.
This paper presents the karyotype of Callicebus donacophilus pallescens for the first time. The analysis included G-, C-, NOR-banding techniques and FISH with chromosome painting probes from Saguinus oedipus and Homo sapiens. The results were compared with the karyotypes of Callicebus moloch donacophilus and C. moloch previously published. These three karyotypes display the same diploid number (2n = 50) but diverge about the number of biarmed and acrocentric chromosomes. The acrocentrics 14 and 15 from C. m. donacophilus and C. moloch have undergone an in-tandem fusion originating a large acrocentric (pair 10) in C. d. pallescens. The major submetacentric pair (pair 1) from C. d. donacophilus and C. moloch have undergone fission originating two acrocentric pairs in C. d. pallescens (pairs 15 and 22). Herein was evidence that, in spite of the high interspecific variation among Callicebus, most of the chromosomes remained conserved.


Single-center trials tend to provide larger treatment effects than multicenter trials: a systematic review.
To assess whether the reported trial characteristics are associated with treatment effects on all-cause mortality within critical care medicine. We identified all eligible randomized controlled trials (RCTs) from Cochrane Reviews on patients with sepsis, septic shock, and cardiogenic shock. Risk of bias was judged on 12 trial characteristics, including the differentiation between single-center and multicenter trials. Hierarchical random-effects models quantified the impact of the risk of bias items on the reported effect estimates of mortality. Twelve meta-analyses that involved 82 RCTs were selected and judged. Single-center trials estimated a significant larger treatment effect compared with multicenter trials (ratio of odds ratios, 0.64; 95% confidence interval: 0.47, 0.87). Treatment effect tended to be overestimated with selective reporting of preplanned end points. Biases in different trial characteristics are unlikely to operate independently and may have modified these associations. The results of this study highlight a substantial difference in treatment effect estimates between single-center and multicenter trials. Therefore, we recommend that results from single-center trials should be cautiously used for decision making.


Removal of lead from contaminated water bodies using sea nodule as an adsorbent.
Adsorption of water soluble lead on polymetallic sea nodule has been studied in detail. Complete decontamination of lead is possible by appropriate sea nodule dosing. Adsorption is also dependent on pH and best adsorption is achieved at pH 6. Beyond pH 6, the desorption of lead from sea nodule surface is practically zero. Residual metal concentrations in the filtrate after adsorption is negligible. Both Freundlich and Langmuir isotherms may reasonably explain adsorption of lead on sea nodule. Chemically bound moisture plays a very crucial role in lead adsorption. Lead adsorptive capability of sea nodule is practically destroyed when calcined at a temperature of 900 degrees C. Lead loading capacity of sea nodule has been estimated at 440 mg of lead per gram of sea nodule. The performance of sea nodule as a lead adsorbent has been successfully tested over six simulated lead contaminated water systems. Lead loading capacity of sea nodule compares favorably with other adsorbents like activated carbon, ion exchange resin, anionic clay, granulated blast furnace slag and natural and treated zeolites.


Prolonged sensitivity to monocular deprivation in dark-reared cats: effects of age and visual exposure.
Previous studies have shown that the response properties of cortical cells of cats reared in darkness throughout the naturally-occurring critical period can still be modified by environmental manipulation. Here the effects of extremely prolonged dark-rearing, and of light exposure before or after dark-rearing on subsequent susceptibility to monocular deprivation are examined. Monocular deprivation remains effective in altering cortical ocular dominance even in cats which have been dark-reared for up to 2 years, long after the end of the naturally occurring critical period. The effects of monocular deprivation are, however, less pronounced in these cats than in animals dark-reared for shorter periods of time. The effects of visual exposure before dark-rearing were examined by allowing kittens 2 months of normal vision followed by 3 months of dark-rearing. Then, the effects of monocular suture were compared among these kittens and: (1) 2-month-old normal kittens (which had the same amount of visual exposure as the experimental animals); and (2) 5-month-old normal kittens (of the same age as the experimental animals). The results show that monocular deprivation is more effective in the experimental animals than in normal kittens of the same age, but less effective than in normal 2-month-old animals. The effects of visual exposure after dark-rearing were examined by allowing animals dark-reared for 4 months varied durations of binocular visual exposure before monocular suture. Susceptibility to monocular suture disappears about 6 weeks after the dark-reared animals are brought into the light.


Poetry and Medicine.
Poetry and medicine are related in multiple ways, including historical interests in healing, defined broadly, through words. More contemporary scholarship explores how poems, which include insights into the human condition, can enlarge our understanding of health, illness, mortality, and health care, including issues of diversity. Anesthesiology and poetry have particular affinities due to their structures, timeframes, and rhythms. Patients, physicians, and health care workers can benefit in terms of well-being by access to reading, reflecting on, and writing poetry.


Challenges To Attenuate Ureteric Stent-Related Symptoms: Reflections On The Need To Fashion A New Dynamic Stent Design Consequent Upon A Case Report.
Double-pigtail stent has been widely used in urology for half a century now, but this device reduces the patient's quality of life. Moreover, indwelling stent-related symptoms induce additional suffering to the pre-existing bladder disease. Novel concepts to prevent stent-related symptoms are greatly required. It has been suggested that changes in the size, form and stent positioning could ease discomfort. By decreasing the amount of material within the bladder, it should be possible to attenuate the stent-related symptoms. A customized stent has been developed to alleviate bladder symptoms. The major characteristic of this stent was in the replacement of the bladder part of the double-pigtail stent by a nonrefluxing silicone end-piece. Three months after stenting, the patient complained of sudden discomfort in the bladder area. On the X-ray, the end-pieces of the customized stents seemed to have slipped in the bladder. The customized stents were replaced by new ones after truncating and adjusting their lengths to the exact ureteric length and stent-related symptoms were then improved again. In the field of stent-related symptoms, stent mobility needs more attention than its intravesical position. The case hereby reported illustrates the variations of the symptoms which seem related to the stent mobility, the necessary shaping of the stent and, the possible research avenues for an innovative dynamic ureteric stent.


Minimally invasive surgery induces endotoxin-tolerance in the absence of detectable endotoxemia.
Lipopolysaccharide (LPS) tolerance is characterized by an impaired proinflammatory cytokine production upon restimulation of mononuclear cells with LPS. LPS is considered the primary activator for this phenomenon. In response to major injury and extensive abdominal surgery, an immune reaction comparable to LPS tolerance has been described. Therefore, it was investigated whether primary stimuli other than LPS could induce cytokine downregulation. In eight patients who underwent a laparoscopic cholecystectomy, blood was obtained before and after induction of anaesthesia and 2, 6, and 24 hr postoperatively. Ex vivo stimulation of whole blood resulted in a transient reduction (nadir 2 hr postoperatively) of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and interferon-gamma release, while IL-1 receptor antagonist production increased. Stress hormones, LPS-binding protein, and bactericidal/permeability-increasing protein do not seem to be involved. This study shows that minimally invasive surgery, in the absence of endotoxemia, can induce LPS desensitization. These data suggest that prior endotoxemia is not essential for the development of LPS tolerance.


Central functions of the lumenal and peripheral thylakoid proteome of Arabidopsis determined by experimentation and genome-wide prediction.
Experimental proteome analysis was combined with a genome-wide prediction screen to characterize the protein content of the thylakoid lumen of Arabidopsis chloroplasts. Soluble thylakoid proteins were separated by two-dimensional electrophoresis and identified by mass spectrometry. The identities of 81 proteins were established, and N termini were sequenced to validate localization prediction. Gene annotation of the identified proteins was corrected by experimental data, and an interesting case of alternative splicing was discovered. Expression of a surprising number of paralogs was detected. Expression of five isomerases of different classes suggests strong (un)folding activity in the thylakoid lumen. These isomerases possibly are connected to a network of peripheral and lumenal proteins involved in antioxidative response, including peroxiredoxins, m-type thioredoxins, and a lumenal ascorbate peroxidase. Characteristics of the experimentally identified lumenal proteins and their orthologs were used for a genome-wide prediction of the lumenal proteome. Lumenal proteins with a typical twin-arginine translocation motif were predicted with good accuracy and sensitivity and included additional isomerases and proteases. Thus, prime functions of the lumenal proteome include assistance in the folding and proteolysis of thylakoid proteins as well as protection against oxidative stress. Many of the predicted lumenal proteins must be present at concentrations at least 10,000-fold lower than proteins of the photosynthetic apparatus.


[Topography of benign nonepithelial tumours of the stomach (author's transl)].
In a series of 500 unselected autopsy cases 23 myomas, 14 neurinomas and 5 lipomas of the stomach were met. Benign tumours are mainly localized in the corpus and fundus of the stomach.


Challenges for precision public health communication in the era of genomic medicine.
Although still in the early stages of development, the advent of fast, high-output, and cost-effective next-generation DNA sequencing technology is moving precision medicine into public health. Before this shift toward next-generation sequencing in public health settings, individual patients met geneticists after showing symptoms and through limited family screening. In the new era of precision public health, everyone is a possible participant in genetic sequencing, simply by being born (newborn screening), by donating blood (biobanking), or through population screening. These initiatives are increasingly offered to individuals throughout their life and more individuals are encountering opportunities to use DNA sequencing. This article raises awareness of these growing areas and calls for different models of public engagement and communication about genomics, including screening asymptomatic populations, obtaining consent for unspecified and unforeseen future uses of genomic data, and managing variants of uncertain significance. Given that such communication challenges loom large, established norms of practice in genomic medicine and research should be reconsidered.


Plasma phospholipid fatty acid and ex vivo neutrophil responses are differentially altered in dogs fed fish- and linseed-oil containing diets at the same n-6:n-3 fatty acid ratio.
The effect of diets containing either 18-carbon n-3 fatty acids (FA) or 20/22-carbon n-3 FA on canine plasma and neutrophil membrane fatty acid composition, superoxide and leukotriene B₄ and B₅ production when fed at the same n-6:n-3 fatty acid ratio was investigated. Four groups of ten dogs each were fed a low fat basal diet supplemented with safflower oil (SFO), beef tallow (BTO), linseed oil (LSO), or Menhaden fish oil (MHO) for 28 days. Dietary fat provided 40.8% of energy and the n-6:n-3 of the diets were ~100:1, 9.7:1, 0.38:1, and 0.34:1 for the SFO, BTO, LSO and MHO groups, respectively. The MHO and LSO groups had increased incorporation of EPA and DPA in both the plasma and neutrophil membranes compared to the BTO and SFO groups. DHA was observed in the MHO but not in the LSO group. Neutrophils from the MHO diet fed dogs had less LTB₄ and greater LTB₅ than the other three groups. The LSO group also showed a reduction in LTB₄ and greater LTB₅ production compared to the SFO and BTO groups. Both LSO and MHO groups had lower superoxide production compared to the SFO and BTO groups. Diets containing 18 or 20/22 carbon n-3 FA fed at the same n-6:n-3 resulted in differential incorporation of long chain n-3 FA into neutrophil membranes. Thus, fatty acid type and chain length individually affect neutrophil membrane structure and function and these effects exist independent of dietary total n-6:total n-3 FA ratios.


Vitamin D and Type 1 Diabetes Risk: A Systematic Review and Meta-Analysis of Genetic Evidence.
Several observational studies have examined vitamin D pathway polymorphisms and their association with type 1 diabetes (T1D) susceptibility, with inconclusive results. We aimed to perform a systematic review and meta-analysis assessing associations between selected variants affecting 25-hydroxyvitamin D [25(OH)D] and T1D risk. We conducted a systematic search of Medline, Embase, Web of Science and OpenGWAS updated in April 2021. The following keywords "vitamin D" and/or "single nucleotide polymorphisms (SNPs)" and "T1D" were selected to identify relevant articles. Seven SNPs (or their proxies) in six genes were analysed: CYP2R1 rs10741657, CYP2R1 (low frequency) rs117913124, DHCR7/NADSYN1 rs12785878, GC rs3755967, CYP24A1 rs17216707, AMDHD1 rs10745742 and SEC23A rs8018720. Seven case-control and three cohort studies were eligible for quantitative synthesis (n = 10). Meta-analysis results suggested no association with T1D (range of pooled ORs for all SNPs: 0.97-1.02; p > 0.01). Heterogeneity was found in DHCR7/NADSYN1 rs12785878 (I2: 64.8%, p = 0.02). Sensitivity analysis showed exclusion of any single study did not alter the overall pooled effect. No association with T1D was observed among a Caucasian subgroup. In conclusion, the evidence from the meta-analysis indicates a null association between selected variants affecting serum 25(OH)D concentrations and T1D.


Symptoms and characteristics of individuals with different types of recovery from DSM-IV alcohol dependence.
Symptoms and criteria for DSM-IV alcohol dependence and demographic and drinking characteristics are compared for three groups. Group I (N = 1,044) consists of persons who formerly met the criteria for dependence but were abstinent in the past year, Group II (N = 2,325) consists of persons who were formerly dependent but did not meet the criteria for abuse or dependence in the past year despite drinking, and Group III (N = 22,204) consists of persons who never met the criteria for dependence. Members of Group II lay between members of Groups I and III in terms of the numbers of prior dependence symptoms and criteria, past level of intake, degree of familial alcoholism and history of alcohol treatment. Both groups of former alcoholics were equally likely to have experienced withdrawal, drinking more/longer than intended and tolerance. The criteria that most strongly distinguished the groups were continued use despite physical or psychological consequences, time spent drinking and activities given up, all of which were far more common in Group I than in Group II. Members of Group II had earlier onsets of heavy drinking and dependence than members of Group I, supporting the existence of a developmentally limited subtype of alcoholism that is subject to spontaneous remission in early adulthood without treatment. The paper compares three options for tightening the criteria for dependence, all of which remove more members from Group II (28% to 41% depending on option) than from Group I (12% to 19%).


Vascular Dysfunctions Contribute to the Long-Term Cognitive Deficits Following COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and "brain fog" are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.


CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation.
Meta-analyses of genome-wide association studies (GWAS) have demonstrated that the same genetic variants can be associated with multiple diseases and other complex traits. We present software called CPAG (Cross-Phenotype Analysis of GWAS) to look for similarities between 700 traits, build trees with informative clusters, and highlight underlying pathways. Clusters are consistent with pre-defined groups and literature-based validation but also reveal novel connections. We report similarity between plasma palmitoleic acid and Crohn's disease and find that specific fatty acids exacerbate enterocolitis in zebrafish. CPAG will become increasingly powerful as more genetic variants are uncovered, leading to a deeper understanding of complex traits. CPAG is freely available at www.sourceforge.net/projects/CPAG/.


Multiple-cue probabilistic learning in spider-fearful and in panic-prone individuals.
Probabilistic learning was studied in spider-fearful and in panic-prone individuals. Participants learned to predict the occurrence of aversive outcomes on the basis of relevant and irrelevant stimuli. The salience of irrelevant stimuli was manipulated by the use of threat-related objects, i.e. pictures of spiders and pictures of emergency situations. In spider-fearful individuals, the presence of irrelevant pictures of spiders interfered with the adequate acquisition of the association between neutral relevant stimuli and aversive outcomes. Salient, i.e. threat-related, irrelevant stimuli exerted competitive effects on the accruing of associative strengths between neutral stimuli and aversive outcomes in spider-fearful, but not in panic-prone, individuals.


Klippel-Trenaunay-Weber syndrome involving fetal thigh: prenatal presentations and outcomes.
We analyzed the prenatal presentations and perinatal outcomes of Klippel-Trenaunay-Weber syndrome involving fetal thigh in order to provide relevant information for prenatal counseling. We reviewed our own cases and searched for cases from Medline that met the criteria of Klippel-Trenaunay-Weber syndrome involving fetal thigh. Those with isolated hemangioma, hemangioendothelioma, and hemangiolymphangioma were excluded. The cases of Klippel-Trenaunay-Weber syndrome involving fetal thigh, totaling 21, were collected for analysis. These included 19 cases from Medline search and two cases from our institution. The cases with lesions involving right thigh, left thigh, and both thighs were 12:8:1. The gender of affected fetuses was 9 male, 9 female, and 3 unknown. Among the 21 cases, 6 fetuses (28.57%, 6/21) had isolated thigh lesions, and the other 15 cases (71.43%, 15/21) had extensive lesions involving pelvis, abdomen, retroperitoneum, or thorax. Prenatal presentations varied with hypoechoic cystic mass with limb asymmetry, 95.23% (20/21); polyhydramnios, 38.09% (8/21); cardiomegaly, 19.04% (4/21); thick placenta, 9.52% (2/21); nonimmune hydrops fetalis, 9.52% (2/21); and oligohydramnios, 4.76% (1/21). Ten cases (47.62%, 10/21) underwent termination of pregnancy. For those who continued with pregnancy, the rate of complications with Kasabach-Merritt syndrome was 36.36% (4/11) and the mortality rate in the neonatal period was 45.45% (5/11). The causes of neonatal mortality in these five cases included consumption coagulopathy (Kasabach-Merritt syndrome), cardiac failure, sepsis, and prematurity. Klippel-Trenaunay-Weber syndrome involving fetal thigh is rare. Our review showed that the location of involvement on the right thigh is more than on the left. Males and females were equally affected. Nearly three fourths of the cases had extensive involvement over other parts of the body. Prenatal ultrasound finding of a raised thigh mass of significant size and limb asymmetry were the most important features. The mortality rate was as high as 45.45% in the neonatal period.


A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease.
A functional --1021C --> T polymorphism in the dopamine beta-hydroxylase gene has been demonstrated to regulate plasma DBH activity. We report that individuals with genetically determined low serum DBH activity (genotype T/T) have protection against Parkinson's disease (p = 0.01). In particular, we observed an underrepresentation of the T/T genotype odds ratio = 0.46 (CI = 0.27-0.8). Rather than identifying a haplotype, or a marker in linkage disequilibrium with the risk variant, this to our knowledge is the first report directly linking PD susceptibility with a proven functional variant.


Randomised, double-blind, placebo-controlled trial of glycopyrronium in children and adolescents with severe sialorrhoea and neurodisabilities: protocol of the SALIVA trial.
Severe sialorrhoea is a common, distressing problem in children/adolescents with neurodisabilities, which has adverse health and social consequences. The SALIVA trial is designed to evaluate the efficacy and safety of a paediatric-specific oral solution of glycopyrronium along with its impact on quality-of-life (QoL), which has been lacking from previous trials of sialorrhoea treatments. A double-blind, placebo-controlled, randomised phase IV trial is ongoing in several centres across France. Eighty children aged 3-17 years with severe sialorrhoea (≥6 on the modified Teachers Drooling Scale) related to chronic neurological disorders in whom non-pharmacological standard of care has already been implemented or has failed, will be recruited. Patients will be randomised 1:1 to receive a 2 mg/5 mL solution of glycopyrronium bromide (Sialanar 320 µg/mL glycopyrronium) or placebo three times daily during a 3-month blinded period. After Day 84, participants will be invited into a 6-month, open-label study extension period, where they will all receive glycopyrronium. The primary endpoint of the double-blind period will be the change from baseline to Day 84 in the Drooling Impact Scale (DIS), a validated measure to assess sialorrhoea. A series of secondary efficacy endpoints involving change in total DIS, specific DIS items and response (DIS improvement ≥13.6 points) will be analysed in a prespecified hierarchy. QoL data will be collected from parents, caregivers and patients where possible using specific DIS questions and DISABKIDS questionnaires. Safety endpoints, including adverse events, will be assessed throughout the trial periods. In total, 87 children have been recruited and recruitment is now complete. Final results are expected by the end of 2023. Findings will be presented at conferences and published in peer-reviewed journals. EudraCT 2020-005534-15.


Mesenteric Defect Closure and the Rate of Internal Hernia in Laparoscopic Roux-en-Y Gastric Bypass: A Systematic Review and Meta-analysis.
Internal hernias are a worrying complication from laparoscopic Roux-en-Y gastric bypass (LRGB), with potential small bowel necrosis and obstruction. An electronic database search of Medline, Embase, and Pubmed was performed. All studies investigating the internal hernia rates in patients whose mesenteric defects were closed vs. not closed during LRGB were analysed. Odds ratios were calculated to assess the difference in internal hernia rate. A total of 14 studies totalling 20,553 patients undergoing LRGB were included. Internal hernia rate (220/12,445 (2%) closure vs. 509/8108 (6%) non-closure) and re-operation for small bowel obstruction (86/5437 (2%) closed vs. 300/3132 (10%) non-closure) were reduced when defects were closed. There was no difference observed when sutures were used to close the defects compared to clips/staples.


[Diagnostic value of R amplitude behavior at a recording site below the conventional thoracic wall recording in the diagnosis of chronic ischemic heart disease].
Sensitivity and specificity of the behaviour of the R-amplitudes under exercise are investigated at an additional lead position on the anterior chest wall, which in previous multi-electrode-examinations showed a higher sensitivity than the conventional Wilson-leads V 4 and V 5. For the criterion "increase of R-amplitudes" could certainly be confirmed a higher sensitivity at the additional lead position, the bad specificity both at the conventional and at the additional lead position allows, however, only the inclusion of the decrease of the physiological R-amplitude into the exclusion diagnostics of the chronic ischaemic heart disease.


Modification of animal habitat by large plants: mechanisms by which seagrasses influence clam growth.
Field experiments withMercenaria mercenaria in a relatively high-energy environment demonstrated that clams on unvegetated sand flats failed to grow during autumn while those within seagrass beds grew substantially. Clam growth rates at the seagrass margin that first receives the faster-flowing, flood-tidal currents were about 25% less than at the opposite edge. In a second experiment, pruning, which reduced average blade length by 50-75%, was shown to enhance near-bottom current velocities and to reduce shell growth ofMercenaria during summer by about 50%. As in the first experiment, clams in the unvegetated sand flats exhibited no net growth. Clam mortality, caused mostly by predatory crabs and whelks, was much higher on sand flats than in seagrass beds and intermediate in clipped seagrass. Although consistent with some previous reports, these growth results are still surprising given that they contradict the generalization that suspension feeders grow faster under more rapid current regimes.Three types of indirect interactions might explain the observed effect of seagrass on growth of buried clams: (1) altering food supply; (2) changing the intensity of biological disturbance on feeding clams; and/or (3) affecting the physical stability of the sediments. Previous research on this question has focused almost exclusively on processes that alter food supply rates. In this study, food concentrations, as indicated by suspended chla, were 30% higher inside than outside one seagrass bed, whereas chla concentrations in two other beds were not different from those on adjacent sand flats. This result is sufficient to show that more intense food depletion was not induced by the reduction in flow velocities under the seagrass canopy. Nevertheless, the possible small difference in food concentrations between vegetated and unvegetated bottom seems insufficient to explain the absence of growth of sand-flat clams, especially given the virtual lack of food limitation among suspension feeders in this system. Two data sets demonstrated that the effects of biological disturbance agents cannot be ignored. An outdoor laboratory experiment showed that even in the absence of physical contact between predator and prey the presence of a whelk reduces the amount of time spent feeding byMercenaria. This result suggests that sand flats, where predation rates are higher, may be sites of lower clam growth than seagrass beds because of greater consumer interference with clam feeding. Furthermore, clam siphons are proportionately larger inside seagrass than on sand flats, implying that siphon nipping may not be as intense inside seagrass. This process, too, would reduce net growth of sand-flat clams. Finally, no explicit test was conducted of the hypothesis that enhanced sediment transport in the absence of flow baffling and root binding by seagrass inhibits net growth of clams on high-energy sand flats. Nevertheless, this is a reasonable explanation for the pattern of enhanced growth of seagrass clams, and could serve to explain the otherwise unexplained pattern of lower clam growth at the edge of the seagrass bed that experiences the faster flood-tidal current velocities. Each broad process, changing fluid dynamics, altering consumer access, and varying sediment stability, represents a mechanism whereby habitat structure, provided by the dominant plant, has an important indirect influence on the functional value of the habitat for resident animals.


Implementation of a referral pathway for cancer survivors to access allied health services in the community.
The growing demands for multidisciplinary cancer survivorship care require new approaches to address the needs of people living after a cancer diagnosis. Good Life-Cancer Survivorship is a self-management support survivorship program delivered by community allied health (AH) services for people diagnosed with cancer. A pilot study established the benefits of Good Life-Cancer Survivorship to help survivors manage their health and wellbeing in the community health setting. This study expanded the program to four community health services and evaluated the implementation outcomes of the referral pathway to the survivorship program. Eligible cancer survivors attending hospital oncology services were referred to the survivorship program. Data was collected between 19/02/2021-22/02/2022 and included allied health service utilisation, consumer surveys, and interviews to understand consumer experience with the referral pathway. Interviews and focus groups with hospital and community health professionals explored factors influencing the referral uptake. Implementation outcomes included Adoption, Acceptability, Appropriateness, Feasibility, and Sustainability. Of 35 eligible survivors (mean age 65.5 years, SD = 11.0; 56% women), 31 (89%) accepted the referral. Most survivors had two (n = 14/31; 45%) or more (n = 11/31; 35%) allied health needs. Of 162 AH appointments (median appointment per survivor = 4; range = 1-15; IQR:5), 142/162 (88%) were scheduled within the study period and 126/142 (89%) were attended. Consumers' interviews (n = 5) discussed the referral pathway; continuation of survivorship care in community health settings; opportunities for improvement of the survivorship program. Interviews with community health professionals (n = 5) highlighted the impact of the survivorship program; cancer survivorship care in community health; sustainability of the survivorship program. Interviews (n = 3) and focus groups (n = 7) with hospital health professionals emphasised the importance of a trusted referral process; a holistic and complementary model of care; a person-driven process; the need for promoting the survivorship program. All evaluations favourably upheld the five implementation outcomes. The referral pathway provided access to a survivorship program that supported survivors in self-management strategies through tailored community allied health services. The referral pathway was well adopted and demonstrated acceptability, appropriateness, and feasibility. This innovative care model supports cancer survivorship care delivery in community health settings, with clinicians recommending sustaining the referral pathway.


Klebsiella pneumoniae C3 lipopolysaccharide mutants obtained by resistance to bacteriophage FC3-9.
Bacteriophage FC3-9 is one of the several bacteriophages of Klebsiella pneumoniae C3 isolated in our laboratory. Mutants resistant to this bacteriophage were isolated and found to be devoid of lipopolysaccharide O antigen, modified in outer-membrane protein composition and sensitive to complement killing (serum-sensitive), unlike the wild-type strain. Serum-resistant mutants were isolated from these strains. They regained the lipopolysaccharide O antigen and the wild-type outer membrane protein composition and became sensitive to bacteriophage FC3-9.


MRI for in vivo diagnosis of cerebral amyloid angiopathy: Tailoring artifacts to image hemorrhagic biomarkers.
Cerebral amyloid angiopathy (CAA) is a frequent age-related small vessel disease (SVD) with cardinal magnetic resonance imaging (MRI) signatures that are hemorrhagic in nature, and include the presence of strictly lobar (superficial) cerebral microbleeds and intracerebral hemorrhages as well as cortical superficial siderosis. When investigating a patient with suspected CAA in the context of intracranial hemorrhage (parenchymal or subarachnoid) or cognitive dysfunction, various MRI parameters influence the optimal detection and characterization (and prognostication) of this frequent SVD. The present report describes the influence of imaging techniques on the detection of the key hemorrhagic CAA imaging signatures in clinical practice, in research studies, and the imaging parameters that must be understood when encountering a CAA patient, as well as reviewing CAA literature.


ESA-FedGNN: Efficient secure aggregation for federated graph neural networks.
Graph Neural Network (GNN) architecture is a state-of-the-art model, which can obtain complete node embedding features and rich data information by aggregating the information of nodes and neighbors. Therefore, GNNs are widely used in electronic shopping, drug discovery (especially for the treatment of COVID-19) and other fields, promoting the explosive development of machine learning. However, user interaction, data sharing and circulation are highly sensitive to privacy, and centralized storage can lead to data isolation. Therefore, Federated Learning with high efficiency and strong security and privacy enhancement technology based on secure aggregation can improve the security dilemma faced by GNN. In this paper, we propose an Efficient Secure Aggregation for Federated Graph Neural Network(ESA-FedGNN), which can efficiently reduce the cost of communication and avoid computational redundancy while ensuring data privacy. Firstly, a novel secret sharing scheme based on numerical analysis is proposed, which employs Fast Fourier Transform to improve the computational power of the neural network in sharing phase, and leverages Newton Interpolation method to deal with the disconnection and loss of the client in reconstruction phase. Secondly, a regular graph embedding based on geometric distribution is proposed, which optimizes the aggregation speed by using data parallelism. Finally, a double mask is adopted to ensure privacy and prevent malicious adversaries from stealing model parameters. We achieve O ( log N log ( log N ) ) improvements compared to O N 2 in state-of-the-art works. This research helps to provide security solutions related to the practical development and application of privacy-preserving graph neural network technology.


Resting Metabolic Rate of Individuals.
The resting metabolic rate (RMR) represents the energy required to sustain normal body functions and homeostasis in an awake individual under ambient thermoneutral conditions and during rest [...].


Postnatal development of cholecystokinin-like immunoreactivity and its mRNA level in rat brain regions.
Developmental changes of preprocholecystokinin mRNA (CCK mRNA) and cholecystokinin-like immunoreactivity (CCK-LI) were examined in rat brain regions (frontal cortex, colliculi, hippocampus, striatum, and cerebellum) using RNA dot blot assays with cholecystokinin (CCK) cDNA and radioimmunoassay, respectively. The CCK-LI levels in all regions examined were very low at birth. Excluding the cerebellum, the levels in these regions increased postnatally and reached adult values at 28 days of age. In contrast to CCK-LI, CCK mRNA levels changed dramatically during development. A considerable amount of CCK mRNA was detected in the frontal cortex and hippocampus at birth. The changes in the level of CCK mRNA in the frontal cortex and colliculi paralleled those of CCK-LI, including a rapid increase from 7 to 14 days of age. The synthesis of CCK mRNA preceded the appearance of CCK-LI. CCK mRNA levels in the hippocampus and striatum exhibited a transient increase, with a peak at 14 days of age. In the adult brain, the CCK mRNA levels were high in the frontal cortex, moderate in the hippocampus and colliculi, and low in the striatum. The cerebellum contained only a negligible amount of CCK mRNA during development. The relatively high level of CCK-LI compared with the low level of CCK mRNA in the striatum supports the idea that most of the striatal CCK-LI is supplied from extrastriatal regions.(ABSTRACT TRUNCATED AT 250 WORDS)


Contraction of hydrated collagen gels by fibroblasts: evidence for two mechanisms by which collagen fibrils are stabilized.
Studies were conducted to learn more about the mechanism by which fibroblasts contract hydrated collagen gels, a process that may be important in the supramolecular organization of the extracellular matrix. Removal of cells from contracted gels by two different methods, treatment with detergent or treatment with trypsin/EDTA solution, had no visible effect on the bundles of collagen fibrils that had been organized in frameworks around and in between the cells. There was, however, a portion of the collagen gels that expanded after the cells were removed. We conclude that during concentration of collagen gels by fibroblasts, rearranged collagen fibrils were stabilized in place by two different mechanisms. At first, the fibrils were mechanically held in place by the cells. Subsequently, the fibrils were stabilized by non-covalent chemical interactions that are independent of cells. A model system for studying collagen gel reorganization in the absence of cells was developed based on centrifugation of the gels. The overall features of collagen gel reorganization by centrifugation were similar to the features of collagen gel contraction by cells. The collagen fibrils of gels reorganized by centrifugation were at first stabilized mechanically and the gels expanded after centrifugation was stopped. With additional time, the collagen fibrils were stabilized by non-covalent chemical interactions, and then the gels no longer expanded after centrifugation was stopped.


The effects of Pluronic block copolymers on the aggregation state of nystatin.
The purpose of this work was to characterize the effect of block copolymer composition on the aggregation state of nystatin in the presence of Pluronic micelles. The critical aggregation concentrations (CACs) of nystatin were determined by dynamic light scattering (DLS). The CAC of nystatin in phosphate-buffered saline was 20 microM at 37 degrees C. Addition of Pluronics significantly increased the CAC of nystatin up to >350 microM at 37 degrees C at the concentrations studied. The CAC values corresponded directly to the size of the Pluronic hydrophobic blocks, and inversely with Pluronic critical micellization concentration (CMC). Predictably, increasing Pluronic concentration and temperature revealed increases in CACs. The micelle-water partition coefficient (P) of nystatin was determined by nystatin fluorescence. The P for nystatin at 37 degrees C was calculated in F68, F98, P105, and F127 to be 15, 21, 73, and 79, respectively. Pluronic micelle core polarity experiments, determined by pyrene fluorescence, revealed decreased polarity with increasing hydrophobic block length and temperature. Thus, nystatin CACs in the presence of Pluronics correlated directly with the partition coefficients, and inversely with core polarity. These results point to the number of micelles in solution as the primary factor responsible for nystatin solubilization by Pluronics.


Out-of-Pocket and Total Costs for Common Hand Procedures From 2008 to 2016: A Nationwide Claims Database Analysis.
Rising patient out-of-pocket (OOP) costs and financial distress have been associated with reduced access to and delays in care. We evaluated whether OOP and total costs for common hand procedures have increased from 2008 to 2016 and identified key drivers of these costs. Using the IBM MarketScan Research Databases, we identified patients who underwent trigger finger release, open carpal tunnel release, thumb carpometacarpal joint arthroplasty, cubital tunnel release, or open treatment of distal radius fracture in the outpatient setting between 2008 and 2016. Patient OOP costs included copayment, coinsurance, and deductible payments. Costs not directly related to medical care, such as transportation and childcare costs, were not included. The overall cost was defined as the sum of the patient OOP cost and insurer reimbursements. We calculated changes in OOP and total overall costs over the study period. We also performed multivariable linear regressions to evaluate the associations between costs and procedure type, insurance type, region, and site of service. The mean patient OOP cost increased by 55% to 71% and the total overall cost increased by 20% to 45%, depending on the procedure, between 2008 and 2016. Facility overall costs increased by 38%, whereas professional overall costs increased by 9%. Procedures performed in an office-based setting were associated with the lowest patient OOP and total overall costs, whereas high-deductible health plans were associated with the highest OOP costs. Patient OOP and total overall costs increased for the most common hand procedures between 2008 and 2016, driven by a substantial increase in facility costs. Office-based procedures were associated with the lowest costs. To alleviate the rising patient cost burden, hand surgeons could incorporate OOP cost considerations into shared decision-making tools, identify patients who may benefit from financial counseling, and shift procedures to an office-based setting.


Stress, Socializing, and Other Motivations for Smoking Among the Lesbian, Gay, Bisexual, Transgender, and Queer Community in New York City.
This study contributes to the emerging literature on lesbian, gay, bisexual, transgendered, and queer (LGBTQ) health disparities and tobacco use by examining the motivations for smoking among the New York City (NYC) LGBTQ population. We used grounded theory and blended methods from 3 grounded theorists-Strauss, Corbin, and Charmaz-for data collection, coding, and analysis. NYC has extensive legislation to prevent smoking; however, the current smoking prevalence of homosexuals is double that of heterosexuals. Study participants were leaders from 23 NYC LGBTQ organizations. Leaders were chosen to establish a relationship with community and to ensure cultural sensitivity. Eligibility criteria required holding a leadership position in an organization serving the NYC LGBTQ community. Interviews were transcribed verbatim and uploaded into Dedoose for analysis. An initial code list was developed from the interview guide. Key themes were identified as the themes with the most number of quotes. Three key themes emerged from our interviews: image, socializing, and stress. Smoking was reported to be a socialization aid and a maladaptive coping technique for stress arising from interactions of conflicting identities. Future smoking cessation interventions among the LGBTQ community should equip smokers with healthy coping mechanisms that address the stressors that arise from the intersections of smokers' many identities.


Distribution, crypticity, stability, and localization of α-L-fucosidase of mouse cauda epididymal sperm.
Sperm-associated and semen-specific isoforms of α-L-fucosidase are thought to function in fertilization in numerous organisms. Here, we report the localization, distribution, crypticity, and stability of this enzyme in mouse cauda epididymal sperm and cauda fluid. Western analysis revealed that the sperm-associated α-L-fucosidase is present as two isoforms (Mr ∼49 and 56 kDa), whereas the cauda fluid α-L-fucosidase shows a single band at 50 kDa. α-L-Fucosidase activity was detected using the fluorogenic substrate 4-MU-FUC. Of the total α-L-fucosidase activity recovered in the cauda epididymal contents, 74% was found in the cell-free cauda fluid and about 7% was found in sperm cells. During capacitation or permeabilization, cryptic intracellular stores of soluble enzyme were released to the supernatant, while leaving bound enzyme concentrated within the small volume of sperm. Moreover, membrane-associated enzyme activity was still detectable in acrosome-reacted cells. Immunofluorescence studies support the presence of α-L-fucosidase (originally localizing at the acrosomal area) at the equatorial segment after the acrosome reaction. α-L-Fucosidase activity of both cauda fluid and sperm at 37°C, 5% CO(2) was relatively stable and detectable up to 72 hr. The stability and appearance of mouse sperm-associated α-L-fucosidase in the equatorial segment after the acrosome reaction suggest that α-L-fucosidase may be involved in sperm-egg interaction.


Predictive value of the Canada Acute Coronary Syndrome risk score for post-acute myocardial infarction infection.
Although rare, infection in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) significantly increases mortality. Therefore, it is important to identify patients at high risk of infection. We aimed to validate the value of the Canada Acute Coronary Syndrome (C-ACS) risk score for predicting infection in such patients. We conducted a prospective cohort study. Consecutive patients with STEMI undergoing PCI at our hospital from January 2010 to June 2016 were enrolled . C-ACS risk score was calculated based on the following clinical parameters (1 point for each): age ≥ 75 years, Killip class >1, systolic blood pressure <100 mmHg, and heart rate > 100 beats/min. The primary outcome was development of post-acute myocardial infarction (P-AMI) infection. A total of 2198 patients were enrolled, of whom 424 (18.5%) developed infection. The incidence of infection, in-hospital mortality, and major adverse clinical events (MACE) were significantly higher in those with a C-ACS risk score ≥2. After adjusting for potential risk factors, C-ACS risk score remained a significant predictor of P-AMI infection (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.92-2.67, p < 0.001), in-hospital mortality, and MACE. Receiver operating characteristic curves demonstrated the C-ACS risk score had good predictive value for P-AMI infection (area under the curve = 0.783, 95% CI = 0.759-0.806, P < 0.001), in-hospital mortality and MACE. The C-ACS risk score was a good predictor of P-AMI infection, and other clinical outcomes.


Novel insights on toxicology of ochratoxin A contaminated diets to skin: Residues, mucus disruption and barrier impairment in teleost model grass carp (Ctenopharyngodon idella).
Ochratoxin A (OTA), a notorious pollutant widely present worldwide, seriously pollutes aquafeeds. This paper aims to explore the toxicity effects of OTA by the way of diet on the skin barrier in grass carp (Ctenopharyngodon idella). Results were shown as follows in the skin: (1) OTA increased the mRNA abundances of uptake transporter proteins (e.g., OAT3) and decreased efflux transporter proteins (e.g., ABCG2), which caused the accumulation of OTA in the skin of grass carp. (2) OTA upregulated the gene expression related to ROS production by enhancing the NOX (1, 2, 4) signaling pathway and decreased the ability to ROS elimination with downregulation of GPx1 (a,b), Trx by inhibiting the PGC1-α/Nrf2 signaling pathway, which caused oxidative damage to the skin. (3) OTA exacerbated apoptosis in the skin by upregulating the expression of apoptosis-related proteins mediated by ways of endoplasmic reticulum stress and mitochondrial apoptosis. Moreover, OTA down-regulated the mRNA and protein abundances of tight junction-related proteins by inhibiting the MLCK signaling pathway, which in turn disrupted the tight junctions. (4) OTA reduced the number of mucous cup cells and decreased f LZ activities and IgM contents, and finally down-regulated the mRNA abundances of mucin (2, 3), LEAP-2 (A, B), and β-defensin (1, 2, 3), which in turn resulted in impairing skin chemical barrier. Moreover, based on the antimicrobial-related indexes (LZ activities and IgM contents), the OTA-safe upper doses were 814.827 and 813.601 μg/kg.


Mutational scanning of the CHCHD2 gene in Han Chinese patients with Parkinson's disease and meta-analysis of the literature.
Building on recent evidence linking the CHCHD2 gene to both familial and sporadic Parkinson's disease (PD), we carried out a case-control study to examine possible associations between the CHCHD2 gene and PD. We sequenced all four coding regions, exon-intron boundaries, untranslated regions and flanking regions of CHCHD2 in 30 patients with familial disease, 554 patients with sporadic disease and 594 healthy controls. All subjects were Han Chinese from western China. We detected the exonic variants p.Pro2Leu, p.Arg18Gln and p.Arg145Gln in six patients with sporadic PD respectively. The p.Pro2Leu variant was more frequent in patients than in controls, but the difference was not significant (OR 2.149, 95%CI 0.393 to 11.753, p = 0.366). Meta-analysis of our data with studies in the literature showed that p.Pro2Leu variants were associated with sporadic PD (OR 2.51, 95%CI 1.53 to 4.11, p = 0.0002), especially in Asian populations (OR 2.92, 95%CI 1.68 to 5.07, p = 0.0001). Our results suggest that CHCHD2 exonic variants are rare among Chinese patients with PD. Meta-analysis of the literature, however, suggests that p.Pro2Leu variants are associated with sporadic disease, particularly in Asian populations.


A truncated Tn916-like element in a clinical isolate of Enterococcus faecium.
A 58.7-kb nonconjugative plasmid (pKQ1) previously reported in a clinical isolate of Enterococcus faecium was found to contain both a tetM and an erythromycin resistance (erm) determinant. The plasmid contained a region homologous to the A, F, H, and G HincII fragments of Tn916. However, the 4.8-kb B fragment of Tn916 which contained the tetM determinant was replaced by a 7.3-kb fragment, and the 3.6-kb HincII C fragment of Tn916 was missing. An element homologous to Tn917 was juxtaposed to the truncated Tn916-like element. The Tn917-like element was similar in size to the erm transposon Tn917 as determined by a ClaI restriction digest which spanned approximately 99% of the transposon. When Bacillus subtilis or Streptococcus sanguis were transformed with pKQ1, no zygotically induced transposition of the tetM element was detected. Similarly no transposition of the Tn917-like element was detected.


Sociotechnical systems as a framework for regulatory system design and evaluation: Using Work Domain Analysis to examine a new regulatory system.
Like most work systems, the domain of adventure activities has seen a series of serious incidents and subsequent calls to improve regulation. Safety regulation systems aim to promote safety and reduce accidents. However, there is scant evidence they have led to improved safety outcomes. In fact there is some evidence that the poor integration of regulatory system components has led to adverse safety outcomes in some contexts. Despite this, there is an absence of methods for evaluating regulatory and compliance systems. This article argues that sociotechnical systems theory and methods provide a suitable framework for evaluating regulatory systems. This is demonstrated through an analysis of a recently introduced set of adventure activity regulations. Work Domain Analysis (WDA) was used to describe the regulatory system in terms of its functional purposes, values and priority measures, purpose-related functions, object-related processes and cognitive objects. This allowed judgement to be made on the nature of the new regulatory system and on the constraints that may impact its efficacy following implementation. Importantly, the analysis suggests that the new system's functional purpose of ensuring safe activities is not fully supported in terms of the functions and objects available to fulfil them. Potential improvements to the design of the system are discussed along with the implications for regulatory system design and evaluation across the safety critical domains generally.


Doctoral prepared nurses in Denmark and their scientific production between 1976 and 2005.
Nursing research in Denmark has evolved over the last 30 years. By 2005, 48 Danish nurses had earned a doctoral degree. The Danish Nurses Organization formalized a strategy for development of nursing research for the period 1999-2002. The strategy was evaluated in 2004. One point in the evaluation was that the nurses' publication of peer-reviewed articles in journals with an Impact Factor did not show in the bibliographic measure used in health sciences. The purpose of this study is to identify the number of Danish nurses holding a doctoral degree by the end of 2005 and to document their scientific production. A descriptive design based on a national register of all nurses in Denmark holding doctoral degrees was used to explore the curricula vitae and publication lists of 38 out of 48 (79%) nurses on the register. Authorship of all 48 graduated nurses was sought in the databases: PubMed and CINAHL. A pattern of growing engagement in publishing peer-reviewed articles was identified among the Danish nurses holding a doctoral degree. Fifty per cent of these doctoral prepared nurses published peer-reviewed papers. The majority apparently pursued a career in health sciences. Nursing as an academic discipline is evolving in Denmark but, with its roots in clinical nursing, scientists may have to be aware of the necessity to prevail as a discipline through scientific production.


Modeling feature-based attention as an active top-down inference process.
Vision is a crucial sensor. It provides a very rich collection of information about our environment. The difficulty in vision arises, since this information is not obvious in the image, it has to be constructed. Wheres earlier approaches have favored a bottom-up approach, which maps the image onto an internal representation of the world, more recent approaches search for alternatives and develop frameworks which make use of top-down connections. In these approaches vision is inherently a constructive process which makes use of a priory information. Following this line of research, a model of primate object perception is presented and used to simulate an object detection task in natural scenes. The model predicts that early responses in extrastriate visual areas are modulated by the visual goal.


Aromatase and neuroinflammation in rat focal brain ischemia.
Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d-aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase expression in male focal ischemia.


Personality disorders (PD) and interpersonal violence (IV) during COVID-19 pandemic: a systematic review.
Not only did the ongoing CoronaVIrus Disease-19 (COVID-19) pandemic cause a massive number of casualties, but also there is growing concern that the burden of its psychological aftermaths will only show up years down the road. This systematic review summarises the existing literature reporting the impact of COVID-19 on personality disorders (PDs)-related violence. MEDLINE and APA PsycINFO were independently searched for relevant studies by two authors. Eligible studies had to be identifiable through database searching, published and fully accessible. This systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. An initial pool of 241 studies were found, out of which 69 met the selection criteria and were, therefore, included. The majority reported a worse Mental Health Outcome (MHO) during the pandemic as related to dysfunctional personality and positive personality traits predicting a better outcome. Furthermore, increased levels of interpersonal violence (IV) and self-directed violence were reported. Further research should be conducted on the reciprocal interaction of PDs and IV during the time of pandemic. Nevertheless, the dramatic impact of restrictive measures on PDs has still to be appropriately addressed.


Coronavirus Disease 2019 Management Strategies in Solid Organ Transplant Recipients.
Solid organ transplant recipients are at high risk of severe coronavirus disease-2019 (COVID-19). If left untreated, it results in high rates of hospitalization, intensive care unit admission and death. Early diagnosis of COVID-19 is essential to ensure the early administration of therapeutics. Treatment of mild-to-moderate COVID-19 with remdesivir, ritonavir-boosted nirmatrelvir, or an anti-spike neutralizing monoclonal antibody may prevent progression to severe and critical COVID-19. Among patients with severe and critical COVID-19, treatment with intravenous remdesivir and immunomodulation is recommended. This review article discusses strategies in the management of solid organ transplant recipients with COVID-19.