Human intestinal diamine oxidase (DAO) activity in Crohn's disease: a new marker for disease assessment?
The key-enzyme for the metabolism of diamines in man is diamine oxidase (DAO). Its highest activities are in the intestinal mucosa, localized in the cytoplasm of the mature enterocytes of the small and large bowel. If the gut is affected by inflammation in Crohn's disease macroscopical changes are observed. This prospective study investigated if these mucosal alterations are also reflected in changes of mucosal diamine oxidase activity and/or mucosal histamine content respectively. Twenty patients (12 female, 8 male; age: means = 31, range 18-49 years) undergoing gut resection because of complications in Crohn's disease (Jan.-Dec. 1988) formed the basis of the study. Tissue samples of the resected material from areas inflamed and histologically not involved in the disease were investigated for diamine oxidase activities and histamine content. Diamine oxidase activities in the mucosa obtained from the macroscopically normal proximal (155.6; (76-393) mU/g (means, range)) and distal (132; (58.5-295) mU/g) resection margins were similar to our previous findings. In all patients, however, samples from the diseased mucosa had significantly (ca. 50%) lower diamine oxidase activities (74.5; (5-262) mU/g) compared to the healthy tissue. Similar differences were found in material obtained either from whole intestinal wall or from the mucosa. The determination of diamine oxidase activity constitutes possibly a more unambiguous and earlier parameter for assessing the extent of the inflamed area than histological disease presentations. Using biopsies the necessary extent of resection could be estimated before operation: this may influence operative strategies and help in the definition of the minimum amount of inflamed gut to be removed.


Determination of iron in cardiac and liver tissues by plasma emission spectroscopy.
A simple plasma emission spectroscopic method for the determination of iron in liver and cardiac tissue is described. Using this technique, iron was extracted quantitatively from liver tissue of mass 14.2 to 65.4 mg wet weight, and heart tissue of mass 5.9 to 27.4 mg wet weight. Iron added to liver as aqueous ferric nitrate was recovered in the range 93 to 108%. Reference ranges for liver and myocardial iron on post mortem tissue gave respectively mean values of 0.841 mg/g dry weight (Range 0.310 to 1.600, n = 37) and 0.340 mg/g dry weight (Range 0.290 to 0.470, n = 8). Data on patients with haemochromatosis and transfusion siderosis are also presented.


Inhibition of erythropoiesis by benzene and benzene metabolites.
Mice were injected sc with benzene or one of its metabolites, phenol, catechol, or hydroquinone. The ability of these compound to inhibit erythropoiesis was quantified by measuring the incorporation of 59Fe into developing erythrocytes. Benzene decreased 59Fe incorporation into developing erythrocytes in a dose-dependent manner. Maximum inhibition was observed when benzene was administered 48 hr prior to initiation of the 59Fe uptake test. The three metabolites of benzene also significantly inhibited 59Fe incorporation when they were administered 48 hr prior to initiation of 59Fe uptake assay. The degree of inhibition observed with the metabolites was not as great as that observed with benzene. Coadministration of the microsomal mixed-function oxidase inhibitor, 3-amino-1,2,4-triazole, abolished the erythropoietic toxicity of benzene and phenol but had no effect on the catechol- or hydroquinone-induced toxicity.


Why laparoscopic adhesiolysis should not be the victim of a single randomized clinical trial.
Randomized controlled trials may provide erroneous conclusions when the null hypothesis is not rejected because of insufficient analysis statistical power. The authors dispute the conclusion of a randomized controlled trial that compared chronic pain relief rates following laparoscopic adhesiolysis and diagnostic laparoscopy and recommended abandoning laparoscopic adhesiolysis. In the trial, the observed difference between pain rates (15%) was inferior to that expected (35%). On the basis of this result, we calculated the 90% confidence interval of the true difference, whose limits of -1% and 31% were found to fall outside the predetermined equivalency interval (-10% to 10%). The trial should therefore not have concluded that the 2 surgical procedures were equivalent. By doing so, it is likely that numerous surgeons have abandoned laparoscopic adhesiolysis on the basis of this statement. In any randomized trial, a calculation of statistical power is required each time that the null hypothesis cannot be rejected.


Toric intraocular lens implantation: 100 consecutive cases.
To evaluate the first 100 consecutive cases of toric posterior chamber silicone intraocular lens (IOL) implantation by 2 community-based ophthalmologists. Two private practices in western Virginia, USA. Data on the first 100 consecutive toric IOL implantations in 81 patients were collected in a prospective manner. Cataract surgery was performed using topical anesthesia and phaco-chop, phaco-flip, or divide-and-conquer phacoemulsification. A Staar AA4203TF or AA4203TL IOL with a 2.00 diopter (D) or 3.50 D toric power was implanted using a lens injector. After the viscoelastic material was removed, the IOL was rotated to the desired orientation. The IOL orientation was assessed postoperatively at 1 day, 1 to 2 weeks, and the last visit. The mean follow-up was 23 weeks +/- 17 (SD). The IOLs performed in a predicable fashion. The mean astigmatism correction with IOLs within 15 degrees of the intended axis was 1.62 D with the 2.00 D IOL and 2.86 D with the 3.50 D IOL. Eleven patients had IOLs that were rotated more than 15 degrees away from the intended axes; in 3, the astigmatism was worse than preoperatively. The mean preoperative refractive and keratometric astigmatism was 2.48 D and 2.11 D, respectively. The mean postoperative astigmatism was 0.87 D and 2.05 D, respectively. At the last follow-up, half the patients had residual refractive astigmatism of 0.50 D or less and 45% had an uncorrected visual acuity of 20/30 or better. Of postoperative patients with a 20/30 visual acuity with or without correction, 52% could see this well no correction. The results show that toric IOL implantation can help an estimated 20% of patients with astigmatism achieve good vision and a reduced need for distance spectacles. If IOL rotation occurs, it is usually during the first week and can be remedied by repositioning the IOL at 1 week.


Transcriptional Responses of the Heat Shock Protein 20 (Hsp20) and 40 (Hsp40) Genes to Temperature Stress and Alteration of Life Cycle Stages in the Harmful Alga Scrippsiella trochoidea (Dinophyceae).
The small heat shock protein (sHsp) and Hsp40 are Hsp members that have not been intensively investigated but are functionally important in most organisms. In this study, the potential roles of a Hsp20 (StHsp20) and a Hsp40 (StHsp40) in dinoflagellates during adaptation to temperature fluctuation and alteration of different life stages were explored using the representative harmful algal blooms (HABs)-causative dinoflagellate species, Scrippsiella trochoidea. We isolated the full-length cDNAs of the two genes via rapid amplification of cDNA ends (RACE) and tracked their differential transcriptions via real-time qPCR. The results revealed StHsp20 and StHsp40 exhibited mRNA accumulation patterns that were highly similar in response to heat stress but completely different toward cold stress, which implies that the mechanisms underlying thermal and cold acclimation in dinoflagellates are regulated by different sets of genes. The StHsp20 was probably related to the heat tolerance of the species, and StHsp40 was closely involved in the adaptation to both higher and lower temperature fluctuations. Furthermore, significantly higher mRNA abundance of StHsp40 was detected in newly formed resting cysts, which might be a response to intrinsic stress stemmed from encystment. This finding also implied StHsp40 might be engaged in resting cyst formation of S. trochoidea. Our findings enriched the knowledge about possible cross-talk of different Hsp members in dinoflagellates and provided clues to further explore the molecular underpinnings underlying resting cyst production and broad temperature tolerance of this group of HABs contributors.


Could anionic LDL be a ligand for RAGE and TREM2 in addition to LOX-1 and thus exacerbate lung disease and dementia?
We recently highlighted the potential of protein glycation to generate anionic (electronegative) surfaces. We hypothesised that these anionic proteins are perceived by the innate immune system as arising from infection or damaged cell components, producing an inflammatory response within the lung involving the receptor RAGE. We now review two other pathologies linked to the innate immune response, cardiovascular disease and dementia that involve receptors LOX-1 and TREM2 respectively. Remarkable similarities in properties between RAGE, LOX-1 and TREM2 suggest that electronegative LDL may act as a pathogenic anionic ligand for all three receptors and exacerbate lung inflammation and dementia.


Discrimination of elevated immunoglobulin concentrations in CSF due to inflammatory reaction of the central nervous system and blood-brain-barrier dysfunction.
Inflammatory reactions of the central nervous system (CNS) are diagnosed by the determination of elevated immunoglobulin concentrations in cerebrospinal fluid (CSF) due to local production of immunoglobulins. However, unspecific disturbances of the blood-brain-barrier (BBB) can also cause an increase of CSF immunoglobulin concentration as a result of filtration from blood serum. The methods described here attempt a more precise characterization of immunoglobulins in CSF and to define that portion of CSF immunoglobulin derived from the CNS. Albumin and the immunoglobulin fractions IgG, IgA and IgM are determined in serum and CSF. The ratio of albumin in serum and CSF is taken as an indicator of BBB function. By the determination of quotients an overproportional immunoglobulin elevation in CSF as expression of an inflammatory reaction of the CNS can be detected. Methodological problems and the definition of normal ranges are discussed.


Application of PBPK Modeling and Simulation for Regulatory Decision Making and Its Impact on US Prescribing Information: An Update on the 2018-2019 Submissions to the US FDA's Office of Clinical Pharmacology.
Since 2016, results from physiologically based pharmacokinetic (PBPK) analyses have been routinely found in the clinical pharmacology section of regulatory applications submitted to the US Food and Drug Administration (FDA). In 2018, the Food and Drug Administration's Office of Clinical Pharmacology published a commentary summarizing the application of PBPK modeling in the submissions it received between 2008 and 2017 and its impact on prescribing information. In this commentary, we provide an update on the application of PBPK modeling in submissions received between 2018 and 2019 and highlight a few notable examples.


Insensitivity of factor V and factor Va to diisopropylfluorophosphate and antithrombin III.
Bovine plasma Factor V and Factor Va, the latter prepared by thrombin or venom activator action on Factor V, are not inactivated by diisopropylfluorophosphate or antithrombin III nor do they form identifiable complexes with either of these reagents. On the basis of these data, it is concluded that bovine Factor V and Factor Va are not serine proteases.


Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster.
Network motifs provided a "conceptual tool" for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a "spatiotemporal network motif," a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts. On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns. Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.


[Gelatinous transformation of the bone marrow: A retrospective monocentric case series of 12 patients].
Gelatinous bone marrow transformation is a rare complication of unknown pathogenesis related to several underlying diseases. It is described as a focal loss of hematopoietic cells and a deposition of eosinophilic gelatinous substance rich in hyaluronic acid. We report a retrospective monocentric study followed by a literature review. We have identified 12 patients with gelatinous transformation from 1999 to 2014. Clinical, biological and cytological data were collected. A bone marrow aspirate was performed for mild to severe pancytopenia (50%), less frequently for monocytopenia. Mean haemoglobin was 10.4g/dL, platelets 126.9G/L and leucocytes 3.82G/L. Gelatinous transformation was found in all patients. We have identified three hematologic malignancies, three cancers, three severe infections, two anorexia nervosa and one kidney injury. Ten patients had undernutrition, 9 out of the 12 patients died within a year due to advanced underlying disease and comorbidities. Gelatinous bone marrow transformation is found in various situations of severe undernutrition including anorexia nervosa, advanced cancers or severe sepsis, especially in HIV infection. The deposition of hyaluronic acid probably reduces haematopoiesis. Due to a complex inflammatory process, it alters the hematopoietic microenvironment and the bone marrow stroma. Severe undernutrition and other mechanisms are reviewed in this study. Gelatinous degeneration is still a rare disorder, indicative of an advanced underlying disease; its recognition could help guide investigations.


Detection and characterization of a rat parotid gland protein kinase that catalyzes phosphorylation of matured destrin at Ser-2.
Destrin, an actin-binding protein, is partly phosphorylated at Ser-2 (numbering on the matured form) in the resting rat parotid gland, and beta-adrenergic or cholinergic stimulation of this gland induces its dephosphorylation. In this study, we searched for the protein kinase involved in phosphorylation of destrin. We developed an assay method for the kinase, using an antibody specific to destrin phosphorylated at Ser-2, and detected the kinase in the rat parotid homogenate. This enzyme was predominantly (93%) present in the soluble fraction, and the enzyme in this fraction was characterized. It had an optimum pH at 6.8 and required 3-5 mM Mg2+ for its maximum activity. Ca2+ (1 mM) had no effect whereas Mn2+ (5 mM) inhibited the enzyme activity by 75%. The apparent Km values for destrin and ATP were 92 microg/ml and 170 microM, respectively. GTP was an inefficient phosphate donor, and cAMP had no effect. Heat-denatured destrin was poorly phosphorylated. Two-dimensional PAGE analysis of destrin phosphorylated with the soluble fraction indicated that it was exclusively phosphorylated at Ser-2. None of the protein kinase inhibitors tested here was specific to this enzyme. At 1 mM, ML-7, Y-27632, KN-93, HA-1077, H-7, and H-8 inhibited the activity by 88, 61, 58, 49, 46, and 42%, respectively. Staurosporine (2 microM) and H-89 (50 microM) inhibited the activity by 48 and 33%, respectively. Heparin (30 microg/ml) had no effect. These results suggest that the rat parotid gland contains a novel, constitutively active, soluble protein kinase catalyzing specific phosphorylation of destrin at Ser-2.


Association of public health insurance with cancer-specific mortality risk among patients with nasopharyngeal carcinoma: a prospective cohort study in China.
Health insurance programs are effective in preventing financial hardship in patients with cancer. However, not much is known about how health insurance policies, especially in Southwest China with a high incidence of nasopharyngeal carcinoma (NPC), influence patients' prognosis. Here, we investigated the association of NPC-specific mortality with health insurance types and self-paying rate, and the joint effect of insurance types and self-paying rate. This prospective cohort study was conducted at a regional medical center for cancer in Southwest China and included 1,635 patients with pathologically confirmed NPC from 2017 to 2019. All patients were followed up until May 31, 2022. We determine the cumulative hazard ratio of all-cause and NPC-specific mortality in the groups of various insurance kinds and the self-paying rate using Cox proportional hazard. During a median follow-up period of 3.7 years, 249 deaths were recorded, of which 195 deaths were due to NPC. Higher self-paying rate were associated with a 46.6% reduced risk of NPC-specific mortality compared to patients with insufficient self-paying rate (HR: 0.534, 95% CI: 0.339-0.839, p = 0.007). For patients covered by Urban and Rural Residents Basic Medical Insurance (URRMBI), and for patients covered by Urban Employee Basic Medical Insurance, each 10% increase in the self-paying rate reduced the probability of NPC-specific death by 28.3 and 25%, respectively (UEBMI). Results of this study showed that, despite China's medical security administration improved health insurance coverage, NPC patients need to afford the high out-of-pocket medical costs in order to prolong their survival time.


Shoulder arthroscopy in the throwing athlete: perspectives and prognosis.
The efficacy of arthroscopy of the shoulder has been demonstrated as both a diagnostic and an operative tool. The throwing athlete has benefited greatly from this procedure. Intra-articular pathology resulting from throwing motion overuse can be visualized and treated, with relatively little morbidity and a rapid rehabilitation phase.


Utility of the 4Ts score in excluding heparin-induced thrombocytopenia in lung transplant recipients.
Heparin-induced thrombocytopenia (HIT) is a prothrombotic complication following heparin exposure. Data is limited on the incidence of HIT and validity of 4Ts score in the solid organ transplant population. This retrospective observational cohort included patients who underwent lung transplant between August 2015 and June 2018 and had a clinical suspicion of HIT with heparin-PF4 testing. The 4Ts score was correlated with the heparin-PF4 antibody and serotonin release assay (SRA) results, with positive SRA considered confirmed HIT. Of 146 patients evaluated, the overall incidence of HIT was low (2(1%)). Fifty-one patients had heparin-PF4 testing and were included in the cohort; 5 (10%) had positive heparin-PF4 and 1 (2%) had confirmed HIT. The median 4Ts score was 3 (3-4). Thirty (59%), 17 (33%), and 4 (8%) patients had low, intermediate, and high risk, respectively. The intermediate/high risk group compared to the low risk group had a higher use of alternative non-heparin anticoagulation [13 (62%) vs 7 (23%); p = 0.0086)] and a higher incidence of thrombosis [13 (62%) vs 1 (3%); p < 0.0001]. No patient with a low 4Ts score had confirmed HIT, supporting the utility of low 4Ts score to exclude HIT diagnosis in lung transplant recipients.


Kinetic properties of microsomal glucokinase of rat liver have been investigated. The enzyme is inhibited by ATP and activated or deinhibited by AMP. It displays properties associated with a typical allosteric enzyme which could realize a feedback control of glycolysis.


Recombinant pseudorabies virus carrying a plasmodium gene: herpesvirus as a new live viral vector for inducing T- and B-cell immunity.
In Balb/c mice, the sterile protective immunity induced by immunization with radiation-attenuated Plasmodium yoelii sporozoites is eliminated by in vivo depletion of CD8+ T lymphocytes, suggesting that cytotoxic T lymphocytes (CTL) against malaria antigens expressed on infected hepatocytes are required for mediating this protective immunity. To produce a vaccine that would induce CTL against the P. yoelii circumsporozoite protein (CS), we constructed an attenuated pseudorabies virus (PRV) containing a gene encoding this protein. Balb/c mice that received three doses of 10(7) plaque-forming units (p.f.u.) of this vaccine intravenously at 3 week intervals developed high levels of antibodies to sporozoites (indirect fluorescent antibody titre = 4096) and CTL against a 16 amino acid epitope (SYVPSAEQILEFVKQI, amino acids 281-296) from the P. yoelii CS protein designated PYCTL1. The cytotoxic activity of the CTL was antigen-specific, MHC-restricted, and dependent on CD8+ T cells. Furthermore, these CTL eliminated P. yoelii-infected hepatocytes from in vitro culture, indicating that they recognize this peptide on the surface of infected hepatocytes. However, all nine mice that were challenged with 200 sporozoites developed a blood-stage malaria infection. We attribute this lack of protection to the great difficulty of inducing sterile immunity against this highly infectious parasite P. yoelii. We conclude that recombinant pseudorabies virus (PRV) worked successfully as a live vaccine vector to induce both antibodies and CTL, albeit non-protective in vivo, and the herpesviruses should be considered as subunit vaccines where T- and B-cell immunity is required.


Contributions of empirical research to medical ethics.
Empirical research pertaining to cardiopulmonary resuscitation (CPR), clinician behaviors related to do-not-resuscitate (DNR) orders and substituted judgment suggests potential contributions to medical ethics. Research quantifying the likelihood of surviving CPR points to the need for further philosophical analysis of the limitations of the patient autonomy in decision making, the nature and definition of medical futility, and the relationship between futility and professional standards. Research on DNR orders has identified barriers to the goal of patient involvement in these life and death discussions. The initial data on surrogate decision making also points to the need for a reexamination of the moral basis for substituted judgment, the moral authority of proxy decision making and the second-order status of the best interests standard. These examples of empirical research suggest that an interplay between empirical research, ethical analysis and policy development may represent a new form of interdisciplinary scholarship to improve clinical medicine.


Learning does not just happen: establishing learning principles for tools to translate resilience into practice, based on a participatory approach.
Theories of learning are of clear importance to resilience in healthcare since the ability to successfully adapt and improve patient care is closely linked to the ability to understand what happens and why. Learning from both positive and negative events is crucial. While several tools and approaches for learning from adverse events have been developed, tools for learning from successful events are scarce. Theoretical anchoring, understanding of learning mechanisms, and establishing foundational principles for learning in resilience are pivotal strategies when designing interventions to develop or strengthen resilient performance. The resilient healthcare literature has called for resilience interventions, and new tools to translate resilience into practice have emerged but without necessarily stipulating foundational learning principles. Unless learning principles are anchored in the literature and based on research evidence, successful innovation in the field is unlikely to occur. The aim of this paper is to explore: What are key learning principles for developing learning tools to help translate resilience into practice? This paper reports on a two-phased mixed methods study which took place over a 3-year period. A range of data collection and development activities were conducted including a participatory approach which involved iterative workshops with multiple stakeholders in the Norwegian healthcare system. In total, eight learning principles were generated which can be used to help develop learning tools to translate resilience into practice. The principles are grounded in stakeholder needs and experiences and in the literature. The principles are divided into three groups: collaborative, practical, and content elements. The establishment of eight learning principles that aim to help develop tools to translate resilience into practice. In turn, this may support the adoption of collaborative learning approaches and the establishment of reflexive spaces which acknowledge system complexity across contexts. They demonstrate easy usability and relevance to practice.


Cold adapted variants of influenza A. II. Comparison of the genetic and biological properties of ts mutants and recombinants of the cold adapted A/AA/6/60 strain.
The genetic and biological properties of 13 recombinant influenza A clones derived at 25 degrees C from the A/AA/6/60-cold variant (by crosses with 4 different wild type strains) were compared with a set of 5-FU induced ts-mutants. The 5-FU mutants had previously been placed into 7 complementation-recombination groups; the A/AA/6/60-cold parent (PI-7) and the 12 cold recombinant clones which were ts were shown to share a lesion with only one of these groups. The parental strain and 5 recombinant clones were evaluated for replication in the lungs and nasal turbinates of hamsters. Each virus appeared to be attenuated; genetic stability correlated with the level of viral replication in the hamster lung, i.e., viruses which grew best showed a tendency to revert to the ts+ phenotype. Characterization of the ts+ revertants for the presence of the cold adaptation property revealed that these viruses exhibited a spectrum of cold adaptation properties. Two viruses, PI-7 (the parental cold variant) and the CR6 recombinant (A/Queensland/6/72) did not revert in either the lungs or nasal turbinates of hamsters.


Treatment of acute lunate and perilunate dislocations.
Acute lunate and perilunate dislocations are uncommon but devastating carpal injuries with a guarded prognosis. This article outlines the pathoanatomy, diagnosis, indications for treatment, technique, and expected results of open reduction and internal fixation.


Is it possible to reveal a typical swallowing pattern for specific skeletal malocclusion types using M-mode sonographic imaging of tongue movements?
The present study aims to compare the M‑mode ultrasound findings of different skeletal malocclusions and to evaluate whether sonographic parameters can be used for the diagnosis of malocclusions. Tongue movements of 36 adolescents aged between 10.37 and 17.29 years (mean 14.25 ± 1.78 years) were assessed using simultaneous two-dimensional real-time B‑mode and M‑mode sonography. The swallowing patterns of the subjects were visualized recording the motion of the tongue surface in the ultrasound images utilizing a fixed scan line through the middle of the tongue. M‑mode scans of tongue motion during empty deglutition were recorded. The parameters range, duration, and speed were computed for the entirety of the swallowing process using M‑mode examination. Findings were evaluated and statistically analyzed. No clear intraindividual repeatability in the M‑mode imaging of the subjects' swallowing process could be observed. Considering the setup used in the study, it was not always possible to distinguish individual swallowing stages in the M‑mode images with regard to the chosen reference points. The average duration, range of motion, and speed of swallowing were found to be 2.43 s, 24.06 mm, and 10.34 mm/s, respectively. The findings showed both intra- and intersubject variability during empty swallowing. With the help of the metrics that could be calculated based on the M‑mode images, it was not possible to differentiate the swallowing acts of different skeletal malocclusion types. It remains unclear whether M‑mode imaging can accurately visualize the swallowing pattern. Therefore, further progress in technology and multidisciplinary work is needed in order to establish diagnostic references regarding swallowing.


Identification of a region in the N-terminus of Escherichia coli Lon that affects ATPase, substrate translocation and proteolytic activity.
Lon, also known as protease La, is an AAA+ protease machine that contains the ATPase and proteolytic domain within each enzyme subunit. Three truncated Escherichia coli Lon (ELon) mutants were generated based on a previous limited tryptic digestion result and hydrogen-deuterium exchange mass spectrometry analyses performed in this study. Using methods developed for characterizing wild-type (WT) Lon, we compared the ATPase, ATP-dependent protein degradation and ATP-dependent peptidase activities. With the exception of not degrading a putative structured substrate known as CcrM (cell-cycle-regulated DNA methyltransferase), the mutant lacking the first 239 residues behaved like WT ELon. Comparing the activity data of WT and ELon mutants reveals that the first 239 residues are not needed for minimal enzyme catalysis. The mutants lacking the first 252 residues or residues 232-252 displayed compromised ATPase, protein degradation and ATP-dependent peptide translocation abilities but retained WT-like steady-state peptidase activity. The binding affinities of WT and Lon mutants were evaluated by determining the concentration of λ N (K(λN)) needed to achieve 50% maximal ATPase stimulation. Comparing the K(λN) values reveals that the region encompassing 232-252 of ELon could contribute to λ N binding, but the effect is modest. Taken together, results generated from this study reveal that the region constituting residues 240-252 of ELon is important for ATPase activity, substrate translocation and protein degradation.


HIF1α-dependent hypoxia response in myeloid cells requires IRE1α.
Cellular adaptation to low oxygen tension triggers primitive pathways that ensure proper cell function. Conditions of hypoxia and low glucose are characteristic of injured tissues and hence successive waves of inflammatory cells must be suited to function under low oxygen tension and metabolic stress. While Hypoxia-Inducible Factor (HIF)-1α has been shown to be essential for the inflammatory response of myeloid cells by regulating the metabolic switch to glycolysis, less is known about how HIF1α is triggered in inflammation. Here, we demonstrate that cells of the innate immune system require activity of the inositol-requiring enzyme 1α (IRE1α/XBP1) axis in order to initiate HIF1α-dependent production of cytokines such as IL1β, IL6 and VEGF-A. Knockout of either HIF1α or IRE1α in myeloid cells ameliorates vascular phenotypes in a model of retinal pathological angiogenesis driven by sterile inflammation. Thus, pathways associated with ER stress, in partnership with HIF1α, may co-regulate immune adaptation to low oxygen.


Dementia of adult polyglucosan body disease. Evidence of cortical and subcortical dysfunction.
To characterize the dementia associated with adult polyglucosan body disease (APBD) and to correlate the cognitive deficits with abnormalities found on magnetic resonance imaging (MRI). Quantitative neuropsychological testing and MRI in one man with APBD and a review of the literature. The dementia of APBD affects cortical and subcortical functions. The cognitive deficits correlate with MRI findings of cortical atrophy and white-matter abnormalities. Neuropsychological testing and MRI are helpful in the evaluation of patients with APBD.


Editorial - COVID-19: Exemplifying the importance and challenges of Acute Medicine.
COVID-19 has challenged healthcare providers and systems. It has dominated the international news agenda for the majority of 2020; arguably opinion becoming more fractured and disparate as the pandemic has evolved. The changing tone of discourse is concerning, although perhaps not surprising.


Medulloblastoma: long-term results for patients treated with definitive radiation therapy during the computed tomography era.
We performed a retrospective evaluation of the patterns of failure and outcome for medulloblastoma patients treated with craniospinal irradiation therapy during the computed tomography (CT) era. The records of 100 patients treated at Memorial Sloan-Kettering Cancer Center between 1979 and 1994 were reviewed. CT scans or magnetic resonance imaging were used to guide surgical intervention and evaluate the extent of resection postoperatively. All patients were treated with conventional fractionation (1.8 Gy/day) and the majority received full-dose neuraxis radiation therapy and > 50 Gy to the primary site. With a median follow-up of 100 months, the median, 5-year, and 10-year actuarial overall survival for the entire group were 58 months, 50%, and 25%, respectively. The median, 5- and 10-year actuarial disease-free survivals were 37 months, 41%, and 27%, respectively. Patients with localized disease (no evidence of disease beyond the primary site) had significantly improved overall (p < 0.02) and disease-free (p < 0.02) survivals compared to those with nonlocalized disease. For patients with localized disease, the 5- and 10-year overall survival rates were 59% and 31%, whereas the disease-free survivals were 49% and 31%, respectively. Disease-free and overall survivals at similar intervals for patients with nonlocalized disease were 29% and 30% (5 years), and 29% and 20% (10 years), respectively. Sixty-four of 100 patients failed treatment. Local failure as any component of first failure occurred in 35% of patients or 55% (35 of 64) of all failures and as the only site of first failure in 14% or 22% (14 of 64) of all failures. For patients presenting with localized disease (n = 68), local failure as any component of first failure occurred in 32% (22 of 68) and in 18% (12 of 68) as the only site. A multivariate analysis showed that M stage was the only prognostic factor to influence overall survival. For disease-free survival, M stage and the extent of resection were prognostic factors. Ventriculoperitoneal shunting and the use of chemotherapy were associated with a poor outcome; however, these results were confounded by the positive impact of chemotherapy in decreasing the risk of extraneural metastases and the use of these therapies in the more advanced patients. These long-term follow-up data represent one of the largest series of patients with complete follow-up who were treated with a consistent radiation therapy treatment policy during the CT era. Local failure in patients with localized disease, the persistent risk of late failures, treatment-related toxicity, and the ever-present risk of secondary malignancies demonstrate the limitations of standard therapies. Strategies used to increase the total dose to the primary site should be pursued along with other adjuvant therapies such as intensive chemotherapy.


Mitochondrial complex IV is lost in neurons in the cuprizone mouse model.
Cuprizone administration in mice leads to oligodendrocyte death and demyelination. The effect is thought to reflect copper-chelation that leads to inhibition of complex IV of the mitochondrial respiratory chain. The effects this drug has on neurons are less well known. To investigate the toxic effects of cuprizone on mitochondria in neurons. Male c57Bl/6 mice were fed 0.2% cuprizone for up to 5 weeks. Cuprizone-fed and control mice were examined at week 1, 3, 5 and 4 weeks after cessation of cuprizone exposure. The brain was examined for myelin, complex I, complex IV and for COX/SDH activities. Mitochondrial-DNA was investigated for deletions and copy number variation. We found decreased levels of complex IV in the cerebellar Purkinje neurons of mice exposed to cuprizone. This decrease was not related to a general decrease in mitochondrial volume or mass, as there were no differences in the levels of complex I or TOMM20. Neurons are affected by cuprizone-treatment. Whether this mitochondrial dysfunction acts as a subclinical trigger for demyelination and the long-term axonal degeneration that proceeds after cuprizone treatment stops remains unclear.


Prostatic adenocarcinoma with cutaneous metastases overlying oestrogen-induced gynaecomastia.
Carcinoma of the prostate gland is the second most frequent malignancy in males, accounting for 17% of cancer in men; between a third and one-half of these patients will have distant metastases at onset, but rarely cutaneous. We now report a case of prostatic adenocarcinoma with such metastases involving the right nipple and periareolar skin, overlying an area of hormone-induced gynaecomastia.


Effects of apitherapy against salivary gland disorder after radioactive iodine therapy for differentiated thyroid cancer.
Sialadenitis and salivary gland disorders are complications of radioactive iodine therapy (RAIT) that affect the quality of life of patients with differentiated thyroid cancer (DTC). The current study aimed to provide evidence on the protective effect of apitherapy on salivary gland function during RAIT in patients with DTC. In total, 120 patients with DTC who underwent total thyroidectomy were divided into the apitherapy group (group A, n = 60) and the control group (group B, n = 60). Group A received 2.5 g of acacia honey three times daily after each meal during admission for RAIT. Statistical analyses were performed using the Saxon test (which is used to evaluate saliva volume) and salivary gland scintigraphy (which is applied to assess maximum uptake ratio and washout ratio). Compared with group B, group A presented with a more significantly positive change in the rate of amount of saliva before and after treatment (P < 0.01). Group B presented a significant decrease in the maximum uptake ratio of the bilateral parotid and submandibular glands on salivary gland scintigraphy (P < 0.05) and washout ratio of all salivary glands (P < 0.05). Group A did not present significant differences in the maximum uptake ratio and washout ratio. Apitherapy can have protective effects against salivary gland disorder associated with RAIT in patients with DTC.


Brain-derived neurotrophic factor prevents neuronal death in vivo.
Developing vertebrate neurons are thought to depend for their survival on specific neurotrophic proteins present in their target fields. The limited availability of these proteins does not allow the survival of all neurons initially innervating a target, resulting in the widely observed phenomenon of naturally occurring neuronal death. Although a variety of proteins have been reported to promote the survival of neurons in tissue culture, the demonstration that these proteins increase neuronal numbers and/or decrease neuronal death in vivo has only been possible with nerve growth factor (NGF). The generalization of the concept that neurotrophic proteins regulate neuronal survival during normal development critically depends on the demonstration that the survival of neurons in vivo can be increased by the administration of a neurotrophic protein different from NGF. We report here that this is the case with brain-derived neurotrophic factor, a protein of extremely low abundance purified from the central nervous system.


Unusual treatment response of a severe dystonia to diphenhydramine.
A 27-year-old man was admitted to the emergency department with a fluphenazine decanoate-induced dystonia. He was treated with 125 mg diphenhydramine IV in four doses and 2 mg benztropine IM. A fluctuating response was observed before continued remission of the dystonia. Possible reasons for variable patient responses to diphenhydramine are discussed.


High-resolution dynamic mapping of the C. elegans intestinal brush border.
The intestinal brush border is made of an array of microvilli that increases the membrane surface area for nutrient processing, absorption and host defense. Studies on mammalian cultured epithelial cells have uncovered some of the molecular players and physical constraints required to establish this apical specialized membrane. However, the building and maintenance of a brush border in vivo has not yet been investigated in detail. Here, we combined super-resolution imaging, transmission electron microscopy and genome editing in the developing nematode Caenorhabditis elegans to build a high-resolution and dynamic localization map of known and new brush border markers. Notably, we show that microvilli components are dynamically enriched at the apical membrane during microvilli outgrowth and maturation, but become highly stable once microvilli are built. This new toolbox will be instrumental for understanding the molecular processes of microvilli growth and maintenance in vivo, as well as the effect of genetic perturbations, notably in the context of disorders affecting brush border integrity.


Respiratory Infections and Anti-Infective Medication Use From Phase 3 Dupilumab Respiratory Studies.
Patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrent respiratory tract infections. Dupilumab targets type 2 inflammation, a common underlying pathophysiology of both conditions, with proven efficacy. To examine investigator-reported respiratory infection adverse events and anti-infective medication use with dupilumab versus placebo in patients with moderate-to-severe asthma or severe CRSwNP. We performed a post hoc analysis of the pivotal phase 3 trials LIBERTY ASTHMA QUEST (NCT02414854) and LIBERTY NP SINUS-52 (NCT02898454) in moderate-to-severe asthma and severe CRSwNP, respectively. Investigator-reported respiratory infection events occurred at a significantly lower incidence in patients treated with dupilumab versus placebo, in both asthma (22% lower; P < .0001; 95% CI 0.71-0.85) and CRSwNP (38% lower; P <.0001; 95% CI 0.51-0.75). Reported upper and lower respiratory tract infection events were numerically or significantly lower in dupilumab-treated patients in both conditions, as were the number of patients experiencing investigator-reported infections. Significantly less systemic anti-infective medication use occurred in dupilumab versus placebo in asthma (24% lower; P < .0001; 95% CI 0.70-0.83) and CRSwNP patients (49% lower; P < .0001; 95% CI 0.43-0.61), and significantly fewer dupilumab-treated patients used anti-infective medications. When examined by season and month, the data indicated that investigator-reported respiratory infections and anti-infective medication use were less frequent in dupilumab- versus placebo-treated patients throughout the calendar year. Dupilumab treatment was associated with a reduced incidence of investigator-reported respiratory infections in patients with moderate-to-severe asthma or severe CRSwNP. Further studies are required to determine the mechanism behind this reduction.


Hormesis, biological plasticity, and implications for clinical trial research.
The present paper identifies a critical factor that leads to false negative results (i.e., failing to indicate efficacy when beneficial results did occur) in randomized human drug trials. The paper demonstrates that human performance can only be enhanced by a maximum of 30-60% as described by the hormetic dose response which defines the limits of biological plasticity. However, human epidemiological/clinical trials typically contain such extensive variability that often requires responses greater than 2-3 times control group responses to show statistical significance. Thus, many potentially beneficial agents may be missed because the clinical trial fails to recognize and take into consideration the limits of biological plasticity. The paper proposes that this hormesis-biological plasticity-clinical trial conundrum can be addressed successfully via the use of a weight-of-evidence methodology similar to that used by regulatory agencies such as EPA in environmental assessment of chemical toxicity.


Clinical Evaluation of the Efficacy and Tolerability of Rigenase® and Polyhexanide (Fitostimoline® Plus) vs. Hyaluronic Acid and Silver Sulfadiazine (Connettivina® Bio Plus) for the Treatment of Acute Skin Wounds: A Randomized Trial.
Compare the efficacy and tolerability of Connettivina® Bio Plus (Group A) gauze and cream, and Fitostimoline® Plus (Group B) gauze and cream for the treatment of acute superficial skin lesions. Single-center, parallel, randomized trial. A block randomization method was used. University of Salerno-AOU San Giovanni di Dio e Ruggi d'Aragona. Sixty patients were enrolled. All patients fulfilled the study requirements. One application of the study drugs every 24 h, and a six-week observation period. Efficacy and tolerability of the study drugs. In total, 60 patients (Group A, n = 30; Group B, n = 30) were randomized; mean age was 58.5 ± 15.8 years. All patients were included in the outcome analysis. Total wound healing was achieved in 17 patients undergoing treatment with Connettivina® Bio Plus and 28 patients undergoing treatment with Fitostimoline® Plus. The greater effectiveness of the latter was significant (p = 0.00104). In Group B, a significantly greater degree of effectiveness was observed in reducing the fibrin in the wound bed (p = 0.04746). Complications or unexpected events were not observed. Both Connettivina® Bio Plus and Fitostimoline® Plus are secure and effective for treating acute superficial skin lesions. Fitostimoline® Plus was more effective than Connettivina® Bio Plus in wound healing of acute superficial skin lesions, especially if fibrin had been observed in the wound bed.


Comparison of microarray and RNA-Seq analysis of mRNA expression in dermal mesenchymal stem cells.
We characterized mRNA expression profiles in normal and psoriatic human dermal mesenchymal stem cells (DMSCs) to provide a reference for future investigation of differential gene expression in DMSCs. Microarray and RNA sequencing (RNA-Seq) analyses both identified 23 differentially expressed genes using both platforms. The results showed comparable upregulation or downregulation for 14/23 genes using either platform and a 100 % coincidence rate was found by real-time PCR. For all of the differentially expressed genes that were verified by real-time PCR, the coincidence rate for RNA-Seq and real-time PCR was significantly higher than that for microarray analysis and real-time PCR (83.3 vs. 37.5 %, P < 0.0001). Furthermore, RNA-Seq revealed the presence of over 2300 novel transcription tags. Relative to microarray analysis, RNA-Seq is more accurate in identifying differentially expressed genes in DMSCs.


Congestive heart failure associated with diabetes mellitus.
A case of typical congestive heart failure associated with diabetes mellitus is reported. The case was diagnosed on the basis of biopsy findings such as basal laminar thickness and of angiographically normal coronary arteries. The therapy, including insulin, resulted in normalization of electrocardiographic abnormalities and improvement of myocardial contractility.


[Prognostic value of E-cadherin, CD34 in the patients with hepatocellular carcinoma].
To study the expression of E-cadherin and CD34 in the tissues of hepatocellular carcinoma (HCC), to discuss the relationship between them and the clinical pathology and evaluate the prognosis of HCC patients. The expression of E-cadherin and CD34 in HCC tissues of 41 patients were examined by two-step methods of PV-6000 of immunohistochemistry. Clinical-pathological data, tumor recurrent rate and survival rate after hepatectomy were recorded and analyzed. The positive expression rate was observed in 48.78% for E-cadherin and 100% for CD34. The decreased E-cadherin expression were significantly associated with larger tumor, the high-dangerous group with invasion and poor differentiation of HCC tissues (chi(2) = 4.1881, 4.8118, 6.2695, P < 0.05). In the group with negative-expression of E-cadherin, the percent of tumor recurrence within 2 years after hepatectomy was higher and the rate of 5 years survival was significantly lower than the positive-expressed group. A significant negative-correlation between the expression of CD34 and the patients' age and the invasion of tumor (t = 1.9371, 1.9010, P < 0.05) were found. There was no relationship between the expression of E-cadherin and CD34 in HCC tissues. The patient with a negative-expression of E-cadherin in HCC tissues has a poor prognosis. No relationship between the expression of CD34 and tumor recurrence and patients' survival and no relationship between the expression of E-cadherin and CD34 was found.


Immunoglobulin gene transcription: molecular mechanisms.
Recently, many of the proteins involved in transcriptional regulation of immunoglobulin genes have been identified, purified and their cDNAs cloned. This detailed molecular information has revealed fascinating similarities among different classes of DNA-binding proteins and has dramatically expanded the number of potential mechanisms for achieving precise tissue- and developmental stage-specific immunoglobulin transcription.


Ultrastructure of failing myocardium due to induced chronic mitral insufficiency in dogs.
Left ventricular failure was produced in dogs by inducing mitral insufficiency and the cardiac muscle was examined for ultrastructural changes in thsese failing hearts after 5-10 months of mitral insufficiency. The left ventricular failure was established by haemodynamic measurements, chest X-ray and examination of the heart. In the failing heart, the increased number of mitochondria showed close approximation with the sarcolemmal membrane in the T-tubules as well as in the intercalated discs (ID); this is in contrast to what is seen in normal hearts, where T-tubules were mostly coupled with sarcoplasmic reticulum. It is possible that in the heart failing on account of mitral insufficiency mitochondria may be taking over the function of the sarcoplasmic reticulum. Although ID were jumbled up in the failing heart, the intercellular gap and specialized membrane junctions (gap and tight junctions, desmosomes) were quite comparable to normal, indicating that intercellular communication at ID in this type of heart failure is probably maintained. Nuclear chromatin in the failing heart was condensed and lined the inner nuclear membrane. Microbodies with a single limiting membrane were frequent and so were lipofuscin granules. The latter could be an end product of degenerative mitochondria. Golgi bodies in the failing heart were also present in locations away from the nucleus.


Intra-abdominal lymphangioma: A case report.
Lymphangioma is a rare, benign congenital malformation of the lymphatic system that usually affects the neck and head in children. Intra-abdominal lymphangioma accounts for less than 5 percent of all cases of lymphangioma. The clinical presentation of intra-abdominal lymphangioma can vary from asymptomatic to nausea, vomiting, and abdominal pain. The diagnosis of intra-abdominal lymphangioma is based on imaging modalities and histopathological examination. The definitive treatment is surgical resection. Here we describe the interesting and rare case of a 29-year-old woman with lymphangioma of the retroperitoneum extending to the root of the mesentery. We focus on the diagnosis and management of this rare tumor by the application of radiological modalities and pathological analysis.


Cytogenetic effect of some anti-tuberculosis drugs in vitro.
The comparative cytogenetic effects of some widely used anti-tuberculosis drugs (PAS Na, PRA, RMA) were estimated depending on the in vitro administered concentrations, in human peripheral blood cultures. The structural chromosomal lesions were randomly distributed between the different chromosome groups of the human karyotype; nearly 10 to 30% of affected cells had more than one lesion per metaphase. In the treatements with PAS Na and PRA the analysis of the frequencies of the cell carring chromosomal aberrations and of the chromosomal lesion types indicated a dose-response correlation. The significance of the results obtained in vitro on the chromosome-breaking effects of anti-tuberculosis agents and the genetic peril is pointed out.


Preliminary results of the cross-sectional associations of sedentary behavior and physical activity with serum brain-derived neurotrophic factor in adults with coronary heart disease.
This is the first study to analyze the association of accelerometer-measured patterns of habitual physical activity (PA) and sedentary behavior (SB) with serum BDNF in individuals with coronary heart disease. A total of 30 individuals (M = 69.5 years; 80% men) participated in this pre-post study that aimed to test a multi-behavioral intervention. All participants underwent standardized measurement of anthropometric variables, blood collection, self-administered survey, and accelerometer-based measurement of PA and SB over seven days. Serum BDNF concentrations were measured using enzyme-linked immunosorbent assay kit. We applied separate multiple linear regression analysis to estimate the associations of baseline SB pattern measures, light and moderate-to-vigorous PA with serum BDNF (n = 29). Participants spent 508.7 ± 76.5 min/d in SB, 258.5 ± 71.2 min/d in light PA, and 21.2 ± 15.2 min/d in moderate-to-vigorous PA. Per day, individuals had 15.5 ± 3.2 numbers of 10-to-30 min bouts of SB (average length: 22.2 ± 2.1 min) and 3.4 ± 1.2 numbers of > 30 min bouts of SB (average length: 43.8 ± 2.4 min). Regression analysis revealed no significant associations between any of the accelerometer-based measures and serum BDNF. The findings of this study did not reveal an association of accelerometer-measured PA and SB pattern variables with serum BDNF in individuals with coronary heart disease. In addition, our data revealed a considerable variation of PA and SB which should be considered in future studies.


Elevated blood lead levels in children are associated with lower erythropoietin concentrations.
Eighty-six children (mean age, 34 months) were studied to determine whether elevated blood lead levels in children are associated with lower erythropoietin concentrations. The median erythropoietin concentration was 5.9 mIU/mL (range, 2.3 to 11.5 mIU/mL), and the median blood lead level was 0.87 micromol/L (18 microg/dL; range, 2 to 84 microg/dL). Blood lead concentration was inversely and independently related to erythropoietin concentration.


Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience.
To compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. A total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. Fifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P = .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P = .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than patients who did not. BRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.


Zebrafish cardiac regeneration-looking beyond cardiomyocytes to a complex microenvironment.
The study of heart repair post-myocardial infarction has historically focused on the importance of cardiomyocyte proliferation as the major factor limiting adult mammalian heart regeneration. However, there is mounting evidence that a narrow focus on this one cell type discounts the importance of a complex cascade of cell-cell communication involving a whole host of different cell types. A major difficulty in the study of heart regeneration is the rarity of this process in adult animals, meaning a mammalian template for how this can be achieved is lacking. Here, we review the adult zebrafish as an ideal and unique model in which to study the underlying mechanisms and cell types required to attain complete heart regeneration following cardiac injury. We provide an introduction to the role of the cardiac microenvironment in the complex regenerative process and discuss some of the key advances using this in vivo vertebrate model that have recently increased our understanding of the vital roles of multiple different cell types. Due to the sheer number of exciting studies describing new and unexpected roles for inflammatory cell populations in cardiac regeneration, this review will pay particular attention to these important microenvironment participants.


COVID-19 disease and nutritional choices: How will the pandemic reconfigure our food psychology and habits? A case study of the Italian population.
In Italy, the spread of the novel coronavirus (SARS-Cov-2) required lifestyle changes that have affected food choices and people's health condition. We explore people's perception of the role of food consumption as a preventive measure and how it reconfigures consumption habits. We conducted an online survey of a representative sample of 1004 Italian citizens. Around 40% of the population perceive that strengthening the immune defences through nutrition is not important to reduce the risk of coronavirus disease 2019 (COVID-19) infection. People with lower levels of perceived importance are slightly younger and have a less healthy lifestyle. They are less worried about the emergency. During the last months, they have bought less food supplements and also intend to decrease their purchase in the next 6 months. In COVID-19 pandemic, scholars underline the importance of having a strong immune system. However, the Italians who attribute less importance to food that helps the immune system seem to differ negatively in their psychological attitude towards the emergency and food consumption. Today, Italians are asked to engage in preventive food practices to protect against possible chronic diseases; exploring their perceptions is important to orient them towards this change.


High Satisfaction Rating by Users of Private-for-profit Healthcare Providers-evidence from a Cross-sectional Survey Among Inpatients of a Private Tertiary Level Hospital of North India.
Evaluation of outcomes can help improve the quality of provision of services within a healthcare setting. There is limited report on patient satisfaction in private-sector in India although they provide three-quarters of healthcare services. The study was designed to report the level of satisfaction among inpatients of a private tertiary care hospital in India. A total of 102 participants were recruited and their socio-demographic, health-seeking behavior, and satisfaction rating on various aspects of healthcare were elicited. A five item Likert scale was used to obtain the satisfaction rating. Data analysis was done with the help of Stata version-9. Proportions for the discrete variables and means with Standard Deviation for the continuous variables were obtained. All the participants were urban and from upper-middle or upper socio-economic strata. The participants reported a high level of overall satisfaction (93%) as well as high satisfaction with physicians (95%), the doctor's interpersonal skills (99%), nursing-care (93%), general services (94%), and pharmacy (88.1%). There was a high level of satisfaction reported by the participants at this tertiary level hospital. This might reflect the actual good quality services being provided by the provider or the nonannoying response, which cannot be ruled out.


Dispersion-free extraction of In(III) from HCl solutions using a supported liquid membrane containing the HA324H+Cl- ionic liquid as the carrier.
By reaction of HCl and the tertiary amine HA324, an ionic liquid denoted HA324H+Cl- was generated and used in the transport of indium(III) from HCl solutions. Metal transport experiments were carried out with a supported liquid membrane, and several variables affecting the permeation of indium(III) across the membrane were tested: stirring speed, metal and acid concentrations in the feed solutions and the carrier concentration in the supported organic solution. The metal transport results were also compared with those obtained using different carriers in the solid support. A model that described indium(III) transport across the membrane was proposed, and the corresponding diffusional parameters were estimated.


Novel receptor-mediated gene delivery system comprising plasmid/protamine/sugar-containing polyanion ternary complex.
Poly(ethylene glycol) (PEG) derivative having both carboxylic acid-, and lactose-side chains (Lac-PEG-C) deposited onto the surface of DNA/protamine (PRT) complex, and the self-assembled ternary complex was obtained. The diameter of the complexes was 180-200 nm, and they showed good size stability even in the high ionic strength solutions. Lac-PEG-C coating reduced their surface electric potential, and effectively avoided the albumin-induced aggregation. DNA/PRT/Lac-PEG-C complex did not coagulate the red blood cells, and their cytotoxicity evaluated by WST-1 was very low. Lac-PEG-C added to the plasmid/PRT complex prior to the incubation with HepG2 cells extremely enhanced the gene-expression, and by the plasmid/PRT/Lac-PEG-C complex prepared at 1:1.5:8 in weight, 56-fold higher expression of luciferase than that without Lac-PEG-C was observed. The treatment with asialofetuin or phenylarsine oxide evidently interfered with the gene-expression. The high gene expression by the plasmid/PRT/Lac-PEG-C ternary complex on the hepatocyte would be attributed to the asialoglycoprotein receptor-mediated endocytosis.


Sleep Deficiency in Obstructive Sleep Apnea.
Sleep deficiency in patients with obstructive sleep apnea includes abnormal quality, timing, and duration of sleep, and the presence of other comorbid conditions. These include insomnia, circadian misalignment disorders, and periodic limb movements of sleep. The co-occurrence of these conditions with obstructive sleep apnea likely plays a role in the pathogenesis, clinical presentation, and management of obstructive sleep apnea. Considering these conditions and their treatment in evaluating sleep deficiency in obstructive sleep apnea may help to improve patient outcomes. However, future research is needed to understand the intersection between obstructive sleep apnea and these disorders.


CD44 is the principal cell surface receptor for hyaluronate.
CD44 is a broadly distributed cell surface protein thought to mediate cell attachment to extracelular matrix components or specific cell surface ligands. We have created soluble CD44-immunoglobulin fusion proteins and characterized their reactivity with tissue sections and lymph node high endothelial cells in primary culture. The CD44 target on high endothelial cells is sensitive to enzymes that degrade hyaluronate, and binding of soluble CD44 is blocked by low concentrations of hyaluronate or high concentrations of chondroitin 4- and 6-sulfates. A mouse anti-hamster hyaluonate receptor antibody reacts with COS cells expressing hamster CD44 cDNA. In sections of all tissues examined, including lymph nodes and Peyer's patches, predigestion with hyaluronidase eliminated CD44 binding.


Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity.
Hepatitis E Virus (HEV) ORF1 encodes the nonstructural polyprotein wherein a role of PCP-domain in ORF1 proteolysis and/or RNA replication still remains contested. A series of ORF1 mutants of HEV-SAR55 replicon were constructed and tested for viability in S10-3 cells. Six of PCP-'cysteine' (C457A, C459A, C471A, C472A, C481A and C483A) and three 'histidine' (H443L, H497L and H590L) mutants were lethal. Further, a highly conserved 'glycine-triad' (G815-G816-G817) in downstream X-domain, homologous to rubella virus protease-substrate (G1299-G1300-G1301) was identified where two of X-mutants (G816V and G817V) turned lethal. However, all ORF1 sequential nucleotide-mutants conserving the amino acids were viable, which clearly showed post-translational regulation of HEV replication by PCP- and X-domains. Moreover, while vector-expressed ORF1-fusion polyprotein yielded a ~191 kDa band in vitro, it produced ~78 and ~35 kDa fragments ex vivo. Collectively, the indispensability and functional effects of 'PCP-catalytic' and 'X-substrate' residues on HEV replication strongly supported a viral protease.


A qualitative study on the attitudes and approaches of Australian clinicians in addressing sexuality after acquired brain injury.
Studies indicate that up to 50% of survivors of acquired brain injury (ABI) experience persistent changes in sexuality. However, research on clinicians' perspectives in addressing sexuality issues post-ABI is limited. This study explored the attitudes and approaches, barriers and facilitators, and training preferences of Australian clinicians in addressing sexuality in individuals post-ABI. Purposive sampling was used to recruit 20 Australian multi-disciplinary clinicians from a related survey study. Semi-structured interviews were conducted and qualitatively analysed using thematic analysis. Three broad themes were identified: ABI results in multi-faceted changes in sexuality; there is a fundamental discomfort in talking about sexuality; and, strategies proposed by clinicians may help to improve sexuality support. Participants also provided suggestions for sexuality training, which they believed should start at university. Most clinicians are aware of sexuality issues post-ABI but fail to adequately address sexuality in individuals post-ABI due to personal levels of discomfort, perpetuated by institutional factors. Therefore, participants believe that changes made at individual and institutional levels may increase sexuality support for individuals with ABI. However, further research on the causes and treatment of sexual problems and patient perspectives is required to provide the evidence-based guidelines and training programs that clinicians require.Implications for rehabilitationUp to half of individuals experience changes in sexuality after ABI that restrict quality of life and relationships.The consequences of ABI and their impacts on sexuality are understood by Australian clinicians but remain largely unaddressed due to individual discomfort, perpetuated by institutional factors.This study suggests that professional training targeted towards understanding, assessing and treating sexuality issues post-ABI may help to reduce the discomfort.Adjustments should also be made at individual, policy and procedural levels to ensure that sexuality is addressed within rehabilitation post-ABI.


Distortion product emissions in humans. II. Relations to acoustic immittance and stimulus frequency and spontaneous otoacoustic emissions in normally hearing subjects.
Multifrequency and multicomponent evaluations of aural acoustic immittance, including tympanometry and acoustic reflex testing, were performed on 44 normal ears to examine the influence of middle ear functioning on the generation and detection of distortion product otoacoustic emissions (DPEs). In the same ears, the prevalence and parametric features of spontaneous and stimulus frequency emissions were also assessed so that their relationship to the detection "thresholds" and amplitudes of corresponding DPEs could be determined. The general outcome was that none of the examined features of acoustic immittance provided an explanation for the discrete, low-amplitude DPE regions observed in about one third of normal ears. Moreover, the presence of typical spontaneous and stimulus frequency emissions in these same "irregular" ears indicated that emission generation and reverse cochlear transmission were also operating normally within these regions of reduced DPEs. Consequently, other, as yet undetermined influences appear to contribute to the DPE variability noted in some ears. Finally, the simultaneous presence of stimulus frequency emissions, but not spontaneous emissions, appeared to reduce the detection "thresholds" and increase the amplitudes of low-frequency DPEs.


Diversity of entomopathogenic fungi near leaf-cutting ant nests in a neotropical forest, with particular reference to Metarhizium anisopliae var. anisopliae.
We investigated the prevalence of entomopathogenic fungi associated with leaf-cutting ant colonies in a small area of tropical forest in Panama. There was a high abundance of Metarhizium anisopliae var. anisopliae near the colonies. Beauveria bassiana was also detected in the soil, Aspergillus flavus in dump material, and six Camponotus atriceps ants were found infected with Cordyceps sp. Based on a partial sequence of the IGS region, almost all of the M. anisopliae var. anisopliae isolates fell within one of the three main clades of M. anisopliae var. anisopliae, but with there still being considerable diversity within this clade. The vast majority of leaf-cutting ants collected were not infected by any entomopathogenic fungi. While leaf-cutting ants at this site must, therefore, regularly come into contact with a diversity of entomopathogenic fungi, they do not appear to be normally infected by them.


Acrodysostosis. A case of peripheral dysostosis, nasal hypoplasia, mental retardation and impaired hearing.
Acrodysostosis--a rare congenital malformation syndrome--is described in a 4 1/2 year old boy with peripheral dysostosis, nasal hypoplasia, mental retardation (PNM syndrome) and impaired hearing. The differential diagnosis includes pseudo (PH)--and pseudo-pseudohypoparathyroidism (PPH). The patient described here had severe peripheral dysostosis, typical of PNM as opposed to the above-mentioned conditions with only moderate peripheral dysostosis. Furthermore, there were no soft tissue calcifications and no intracranial calcification as can be seen in PH and PPH. Laboratory findings were normal.


Net Assimilation Rate and Agronomic Efficiency of Nitrogen in Tartago (Ricinus communis L.) (Euphorbiaceae) in Dry Climate.
To know the dynamics of net assimilation rate and the agronomic efficiency of nitrogen in the Tartago crop, seeds of three accessions were collected in Teotitlán de Flores Magón, Oaxaca, Mexico. The treatments consisted of nitrogen fertilization of 0, 20, 40, 60, 80, 100, 120, and 140 kg (N) ha-1, evaluated under a completely randomized design. The experimental unit was constituted by a Tartago plant inside of a polyethylene bag with soil of the zone, and four repetitions were considered. The response variables were dry biomass, number of fruits per plant, agronomic yield, harvest index, nitrogen agronomic efficiency, SPAD units, and net assimilation rate. The results indicate that climatic conditions did not influence the growth and development of the crop. The maximum values for all of response variables were achieved with the application of nitrogen in a range of 60 to 140 kg ha-1. The net assimilation rate was adjusted to a quadratic model. It is concluded that the Tartago responds positively to the application of nitrogen and can be an alternative to be grown in dry climate.


Mandibular etymologies.
Many of us can remember how much our vocabulary grew as undergraduates and indeed has continued to grow as dental professionals. For many of us not trained in Latin and Greek we have often been too busy learning what the word means to understand why it means what it does. This article aims to clarify things a little. It explains where words relating to the mandible come from, why we use them now and also shows how they are related to other similar words in everyday use.


Advantages of the scapular system in mandibular reconstruction.
Fibula free flaps (FFF) are often considered the first choice for mandibular reconstruction, but scapular system free flaps (SFF) have increased in popularity due to versatility, donor site advantages, and patient factors. Retrospective chart review of patients undergoing mandibulectomy with FFF or SFF reconstruction from 2016 to 2021. Hundred and seventy-six patients (FFF n = 145, SFF n = 31) underwent the aforementioned procedures. Mean FFF operative time was 9.47 h versus 9.88 for SFF (p = 0.40). Two-flap reconstructions required 12.65 h versus 10.09 for SFF with soft tissue (p = 0.002). Donor site complications were identified in 65.6% of FFF with skin grafting. These findings suggest that SFF requires similar operative time and results in reduced donor site morbidity as compared to FFF. Supine, concurrent harvesting of SFF allows for single-flap harvest with significantly shorter operative time. SFF could be considered a primary option for mandible reconstruction for complex defects and in select patients.


Site-Specific Antibody Fragment Conjugates for Reversible Staining in Fluorescence Microscopy.
Antibody conjugates have taken a great leap forward as tools in basic and applied molecular life sciences that was enabled by the development of chemoselective reactions for the site-specific modification of proteins. Antibody-oligonucleotide conjugates combine the antibody's target specificity with the reversible, sequence-encoded binding properties of oligonucleotides like DNAs or peptide nucleic acids (PNAs), allowing sequential imaging of large numbers of targets in a single specimen. In this report, we use the Tub-tag® technology in combination with Cu-catalyzed azide-alkyne cycloaddition for the site-specific conjugation of single DNA and PNA strands to an eGFP-binding nanobody. We show binding of the conjugate to recombinant eGFP and subsequent sequence-specific annealing of fluorescently labelled imager strands. Furthermore, we reversibly stain eGFP-tagged proteins in human cells, thus demonstrating the suitability of our conjugation strategy to generate antibody-oligonucleotides for reversible immunofluorescence imaging.


A band-tunable, multichannel amplifier for neural recording with AP/LFP separation and dual-threshold adaptive AP detector.
This article presents a low-power low-noise neural recording system comprising a set of 4-channel amplifiers and a dual-threshold adaptive action potential detector. The front-end amplifier is optimized for power efficiency, noise, and silicon area. A balanced tunable pseudo-resistor is used to acquire local field potential (LFP) and action potential (AP) separately. The post-layout simulation results show that the system achieved input referred noise 4.7 μVrms and noise efficiency factor (NEF) 2.79 with mid-band gain of 51.9 dB and power consumption of 5.22 μW. The bandwidth is highly tunable in the range of 2.38 Hz-300 Hz for high-pass corner and 248 Hz-12.9 kHz for low-pass corner, which can acquire AP and LPF without out-band noise. The proposed dual-threshold adaptive AP detector can capture action potential precisely from background activity, thus data reduction can be realized by only processing these significant waveforms. The results show that the proposed low-power, low-noise biomedical system is suitable for implantable device applications.


Training Radiology Residents, Bloom Style.
Bloom's Taxonomy, an integral component of learning theory since its inception, describes cognitive skill levels in increasing complexity (Remember, Understand, Apply, Analyze, Evaluate, and Create). Considering Bloom's Taxonomy when writing learning objectives and lecture material, teaching residents at the workstation and creating multiple choice questions can increase an educator's effectiveness. The incorporation of higher Bloom levels aids in cultivating critical thinking skills vital to image interpretation and patient care, and becomes increasingly important as the radiologist's role evolves with the continued development of artificial intelligence. Following established tenets of multiple choice question writing, involving trainees in the question writing process, and incorporating audience response systems into lectures are all strategies in which higher Bloom level skills can be accomplished.


12-months prospective Pentraxin-3 and metabolomic evaluation in multiple sclerosis patients treated with glatiramer acetate.
Pentraxin-3 (PTX-3) is involved in acute immunological responses and it is a pro-inflammatory protein and a novel biomarker of inflammatory diseases. It is demonstrated that PTX-3 is higher in cerebrospinal fluid (CSF) of aggressive Multiple Sclerosis (MS). Metabolomics, the identification of small endogenous molecules, offers a molecular profile of MS. Glatiramer acetate (GA) is a widely used treatment for (MS) but its mechanism of action is not completely defined. The aim of our study is to analyze PTX-3 and metabolomic profile in MS patients compared to controls and to investigate the effect of GA on PXT-3 and metabolic molecules during treatment in responder and not responder MS patients. 28 unrelated MS patients and 27 age-and sex-matched controls were recruited. In serum, PTX-3 levels were measured by ELISA and Metabolomic panel was evaluated trough Nuclear Magnetic Resonance (NMR). According to clinical practice patients started GA treatment; PTX-3 and metabolomic identification were performed before and during treatment. Responders to treatment were identified if no evidence of instrumental, clinical relapses and disability progression (NEDA) occurred during follow up. Serum PTX-3 levels were higher in MS patients compared to matched controls (7,85 ± 2,19 vs 6,20 ± 1,63 ng/ml) (p = 0,03); metabolomic evaluation shows higher levels of lactate and lower levels of valine, tyrosine and tryptophan in MS patients compared to controls. During therapy, PTX-3 levels have been reduced statistically significant (p = 0,001) at six months and one year of treatment. After one year, of the twenty patients that completed the study, 55% were considered fully responders to treatment; in these patients the mean reduction of PTX-3 at one year was higher respect to not responders (-3,82 ± 1,24 ng/ml vs -2,32 ± 1,03 ng/ml p = 0,02) and we observed a higher reduction of lactate, tyrosine and hypoxanthine and an increase of hydroxyproline and ADP as well as of three oxidative phosphorylation markers, citrulline, ornithine and tryptophan approaching the metabolic profile of healthy subjects. We demonstrated a metabolomic imbalance with mitochondrial dysfunction detected by higher levels of lactate and lower levels of tryptophan, tyrosine and valine in MS patients compared to healthy controls. The reduction of PTX-3 levels and the restoring of mitochondrial function, reducing oxidative stress by GA, allows to identify responder patients. Further and larger studies are needed to understand the predictive role of PTX-3 and metabolomic pattern in the identification of responder patients to GA.


Involvement of nitric oxide in adenosine release in the developing and adult mouse hippocampus.
The novel type of neurotransmitter/neuromodulator nitric oxide (NO) is linked to activation of the N-methyl-D-aspartate (NMDA) class of glutamate receptors and has been shown to modify transmitter release in the brain. The inhibitory neuromodulator adenosine has been thought to act as an endogenous neuroprotectant against cerebral ischemia and neuronal damage. The effects of NO-generating compounds on the release of preloaded [3H]adenosine from hippocampal slices from developing (7-day-old) and adult (3-month-old) mice were investigated, using a superfusion system, under normal conditions and in vitro ischemia. The release of adenosine was markedly potentiated at both ages by the NO-producing compounds S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and hydroxylamine. The evoked releases were reduced by the NO synthase inhibitors nitroarginine and 7-nitroindazole at both ages. They were also reduced by the inhibitor of soluble guanylyl cyclase 1H-(1,2,4-oxadiazolo(4,3a)quinoxalin-1-one (ODQ) in adults, indicating that the NO/cGMP pathway is involved in this release. Release of adenosine was also evoked when the cGMP levels were increased by superfusing slices with the phosphodiesterase inhibitor zaprinast. The markedly enhanced adenosine release under ischemic conditions was further potentiated by the ionotropic glutamate receptor agonists and NO-generating compounds, whereas zaprinast and ODQ had no effect, rendering unlikely the involvement of cGMP in the ischemic release. Moreover, NO was able to provoke substantial release of adenosine in the presence of NMDA under both normal and ischemic conditions, which could significantly add to the neuroprotective potential of this neuromodulator in both adult and developing hippocampus.


Nanotechnology in Cancer Diagnostics and Therapeutics: A Review.
Cancer is the uncontrolled proliferation of cells that involves accumulation of genetic mutations by different types of mutagens including physical, chemical, and biological. Consequently, normal cell cycles get interrupted. Immunological assays, histopathological tests, polymerase chain reaction, computed tomography, magnetic resonance, and radiation therapy are some conventional techniques for cancer diagnostics. However, these techniques are not only expensive, time-consuming, tedious but also toxic to healthy cells. Therefore, these limitations are overcome by nanodevices that show high sensitivity, selectivity, rapidity, and cost-effectiveness in the detection of cancer biomarkers. Electrochemical biosensors are more efficient in the early diagnosis of cancers that help in patients' effective and timely treatment. Distinct types of nanotools viz. inorganic, organic, and polymeric nanomaterials are used in cancer therapeutics. Nano approaches have shown many advantages: they are site-specific, require meager amounts of drugs, limited toxicity, avoid drug resistance, and are more efficient, sensitive, and reliable. Therefore, future research should focus on developing highly inventive nanotools for the diagnosis and therapeutics of cancers.


Oleosins: A Short Allergy Review.
In patients having a history of anaphylaxis after consumption of peanuts, sunflower seeds, or soy and skin or blood tests negative for the allergen extracts, oleosins could be the culprit. Oleosins are common and largely underestimated allergy inducers of plant origin, causing severe allergy symptoms, including the anaphylactic shock. They are resistant to high temperatures and digestive enzymes. The consumption of heat-treated oleosins has been associated with a higher risk of a severe anaphylactic reaction. Recent studies have shown that oleosins could be a biomarker of the allergy severity to peanuts. Oleosins have a hydrophobic structure and thus, are poorly soluble in aqueous solutions. The aqueous extraction, separation, and purification procedures do not guarantee their solubility. Oleosins dissolve only in the presence of detergents, which limits their use in both in vivo and in vitro allergy tests. Recently, a multiparameter allergy test that detects the allergen-specific immunoglobulin E (sIgE) against oleosins has become available. This capability may help to unravel the presence of oleosin source during the routine diagnostic of allergy, which is conducive to assessing the risk for severe anaphylaxis and may also help to clarify the ambiguous allergy cases.


Relationships between the tubular system in the globules of the coronet cells of the saccus vasculosus and the cerebrospinal fluid in Gasterosteus aculeatus form leiurus (Teleostei).
In the stickleback, Gasterosteus aculeatus, the globules of the coronet cells in the saccus vasculosus contain a tubular system that most probably communicates permanently with the lumen of the saccus. Only very few openings were found in random ultrathin sections. Injecting peroxidase into the cerebrospinal fluid revealed the communication between this tubular system and the cerebrospinal fluid. As early a 1 h after peroxidase injection the tracer was detected in the tubular system. This system increases the potential exchange surface between the coronet cells and the content of the saccular lumen, and may also facilitate the access of components of the cerebrospinal fluid (CSF), even of high molecular weight, into the globules. It remains to be determined whether the intratubular condensations (granules) are, as often believed, of secretory origin or are formed by accumulation of components of the CSF.


The asynchronous influence of facial expressions on bodily expressions.
The ability to extract correct emotional information from facial and bodily expressions is fundamental for the development of social skills. Previous studies have shown that bodily expressions affect the recognition of basic facial expressions dramatically. However, few studies have considered the view that facial expressions may influence the recognition of bodily expressions. Further, previous studies have failed to consider a comprehensive set of emotional categories. The present study sought to examine whether facial expressions would impact the recognition of bodily expressions asynchronously, using four basic emotions. Participants performed an affective priming task, in which the priming stimuli included four facial expressions (happy, sad, fearful, and angry), and the target stimuli were bodily expressions matching the same emotions. The results indicated that the perception of affective facial expressions significantly influenced the accuracy and reaction time for body-based emotion categorization, particularly for bodily expression of happiness. The recognition accuracy of congruent expressions was higher, relative to that of incongruent expressions. The findings show that facial expressions influence the recognition of bodily expressions, despite the asynchrony.


Reconfirmation of the symbiosis on carbon emissions and air pollution: A spatial spillover perspective.
Many studies have confirmed the co-emission characteristics of air pollution and carbon emissions. However, studies on the evolution and synergistic factors of the symbiosis of air pollution and carbon emissions over long time scales from a spatial spillover perspective are rare. Here, we identify the spatial evolution and agglomeration characteristics of carbon emissions and air pollution symbiosis by applying local autocorrelation analysis and geographical concentration and by using the dynamic spatial autoregressive model for multiple synergistic factors at city levels during 2006-2019 in China. The results are: (1) The spatial agglomeration and symbiosis of carbon emission and air pollution are similar and show strong spatial locking, as well as path-dependent properties. (2) The spatial imbalance of carbon emission agglomeration and pollution agglomeration gradually improved over time; the concentration centers are all located in Henan province, shifting northward. (3) The symbiosis between both carbon emission agglomeration and pollution agglomeration has significant "spatial and temporal scale effects", and the economic growth is nonlinear. Additionally, innovation vitality has a negative synergistic driving effect on this relationship. In addition to the results above, rapid industrialization and urbanization are taking place in China. Hence, serious actions against greenhouse gases and air pollutants are imminently needed.


Manual dexterity in school-age children measured by the Grooved Pegboard test: Evaluation of training effect and performance in dual-task.
Manual dexterity is the ability to manipulate objects using the hands and fingers for a specific task. Although manual dexterity is widely investigated in the general and special population at all ages, numerous aspects still remain to be explored in children. The aim of this study was to assess the presence of the training effect of the execution of the Grooved Pegboard test (GPT) and to measure the performance of the GPT in dual-task (DT), i.e., during a motor task and a cognitive task. In this observational, cross-sectional study manual dexterity was assessed in children aged between 6 and 8. The procedure consisted of two phases: (1) the execution of five consecutive trials of the GPT to evaluate the training effect; (2) the execution of one trial of the GPT associated with a motor task (finger tapping test, GPT-FTT), and one trial of the GPT associated with a cognitive task (counting test, GPT-CT) to evaluate the performance in DT. As for the training effect, a significant difference (p < 0.001) between the five trials of the GPT (i.e., GPT1, GPT2, GPT3, GPT4, GPT5) was detected. In particular, we found a significant difference between GPT1 and GPT3 (p < 0.05), GPT1 and GPT4 (p < 0.001), and GPT1 and GPT5 (p < 0.001), as well as between GPT2 and GPT4 (p < 0.001), and GPT2 and GPT5 (p < 0.001).As for the performance in DT, no differences between the best trial of the GPT (i.e., GPT5) and both the GPT-FTT and GPT-CT was found. Our findings suggest that the execution of the GPT in children has a training effect up to the third consecutive trial. Furthermore, the administration of the GPT in DT does not affect GPT performance.


Diversity in magnetic properties of 3D isomorphous networks of Co(II) and Mn(II) constructed by napthalene-1,4-dicarboxylate.
Two novel 3D isomorphous organic-inorganic hybrid frameworks, [M(1,4-napdc)]n ( M = Co(II), and Mn(II), ; 1,4-napdcH2 = napthalene-1,4-dicarboxylic acid) have been hydrothermally synthesized and structurally characterized, and the magnetic results exhibit metamagnetic behaviour (TC = 5.5 K), and a weak antiferromagnetic interaction, which are structurally correlated.


Two new species of Oobius Trjapitzin (Hymenoptera, Encyrtidae) egg parasitoids of Agrilus spp. (Coleoptera, Buprestidae) from the USA, including a key and taxonomic notes on other congeneric Nearctic taxa.
Oobius Trjapitzin (Hymenoptera, Encyrtidae) species are egg parasitoids that are important for the biological control of some Buprestidae and Cerambycidae (Coleoptera). Two species, Oobiusagrili Zhang & Huang and Oobiuslongoi (Siscaro), were introduced into North America for classical biocontrol and have successfully established. Two new native North American species that parasitize eggs of Agrilus spp. (Buprestidae) are described and illustrated from the USA: Oobiusminusculus Triapitsyn & Petrice, sp. n. (Michigan), an egg parasitoid of both Agrilussubcinctus Gory on ash (Fraxinus spp.) and Agrilusegenus Gory on black locust (Robiniapseudoacacia L.) trees, and Oobiuswhiteorum Triapitsyn, sp. n. (Pennsylvania), an egg parasitoid of Agrilusanxius Gory on European white birch (Betulapendula Roth). A taxonomic key and notes on the Nearctic native and introduced Oobius species are also included.


CD8 T-cell-based immunotherapy of cytomegalovirus infection: "proof of concept" provided by the murine model.
Adoptive transfer of antiviral effector or memory CD8 T cells is a therapeutic option for preventing acute cytomegalovirus (CMV) disease after primary or recurrent infection in immunocompromised recipients of hematopoietic stem cell transplantation (HSCT) aimed at curing hematopoietic malignancies. Preclinical research in murine models has demonstrated the power of CD8 T-cell-based preemptive immunotherapy and has encouraged clinical trials that gave promising results. The clinical evidence, however, is based primarily on statistical analyses indicating a reduced incidence of CMV-associated complications. Here, we will briefly review the data obtained from the murine model showing that CD8 T cells derived from CMV-immune donors and administered either as peptide-selected cytolytic T lymphocyte lines or after ex vivo purification by T-cell-receptor-specific cell sorting can indeed prevent CMV-mediated histopathology and multiple organ failure.


Diagnosing Hidradenitis Suppurativa.
Three diagnostic criteria must be met for hidradenitis suppurativa: typical lesions, occurrence in one or more of the predilection areas, and that it is chronic and/or recurrent. Several outcome measures are used, including patient-reported pain and itch scales, Dermatology Life Quality Index, and Skindex. Hidradenitis suppurativa is associated with significant comorbidities that must be addressed in the evaluation of the patients.


Psychiatric disorder associated with vacuum-assisted breast biopsy clip placement: a case report.
Vacuum-assisted breast biopsy is a minimally invasive technique that has been used increasingly in the treatment of mammographically detected, non-palpable breast lesions. Clip placement at the biopsy site is standard practice after vacuum-assisted breast biopsy. We present the case of a 62-year-old woman with suspicious microcalcifications in her left breast. The patient was informed about vacuum-assisted breast biopsy, including clip placement. During the course of taking the patient's history, she communicated excellently, her demeanor was normal, she disclosed no intake of psychiatric medication and had not been diagnosed with any psychiatric disorders. Subsequently, the patient underwent vacuum-assisted breast biopsy (11 G) under local anesthesia. A clip was placed at the biopsy site. The pathological diagnosis was of sclerosing adenosis. At the 6-month mammographic follow-up, the radiologist mentioned the existence of the metallic clip in her breast. Subsequently, the woman presented complaining about "being spied [upon] by an implanted clip in [her] breast" and repeatedly requested the removal of the clip. The patient was referred to the specialized psychiatrist of our breast unit for evaluation. The Mental State Examination found that systematized paranoid ideas of persecutory type dominated her daily routines. At the time, she believed that the implanted clip was one of several pieces of equipment being used to keep her under surveillance, the other equipment being her telephone, cameras and television. Quite surprisingly, she had never had a consultation with a mental health professional. The patient appeared depressed and her insight into her condition was impaired. The prevalent diagnosis was schizotypal disorder, whereas the differential diagnosis comprised delusional disorder of persecutory type, affective disorder with psychotic features or comorbid delusional disorder with major depression. This is the first report of a psychiatric disorder being brought to the fore using a vacuum-assisted breast biopsy clip. Vacuum-assisted breast biopsy, and breast biopsy in general, represent a significant experience, encompassing anxiety and pain; it may thus aggravate psychiatric conditions. Apart from these well-established factors, other aspects, such as the clip, may occasionally become significant. In a modern breast unit, the evaluation of patients should be multidisciplinary. A psychiatrist may be needed for optimal management of anxiety-related issues, as well as for the detection of psychiatric disorders.


The depth measuring videomicroscope (DMV): a non-invasive tool for the assessment of capillary vascular malformations.
The response of capillary vascular malformations (CVMs) to laser treatment is believed to be due to the pattern of capillary ectasia, the depth, diameter, and flow through these capillaries and the amount of competing chromophores within the skin. Videomicroscopy has successfully been used to determine CVM capillary pattern and diameter of vessels. The depth measuring videomicroscope (DMV) allows the depth of capillaries to be measured also. The aim of this study is to examine how capillary depths within a CVM are affected by dye laser treatment using DMV. Thirteen previously untreated patients were examined in a temperature-controlled room. A DMV examination was carried out prior to and 6 weeks following a treatment with pulsed dye laser. A further cohort of 11 resistant CVM patients, who had all received over five treatments, was also examined for comparison. Using a Wilcoxon Signed rank test, the results showed that the remaining vessels within the CVM as measured using DMV were more deeply located and smaller (P < 0.01 and P < 0.02 respectively), following the laser treatment. Also in the resistant patients the vessels were again more deeply placed and smaller. The hypothesis that smaller and more deeply placed CVM vessels respond poorest to laser treatment is supported by these findings. Moreover, the DMV provides a simple non-invasive technique for demonstrating this.