Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus.
Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication.IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against most PDAC cells, some are highly resistant to VSV, and the mechanisms are still unclear. Here we examined if VSV attachment to cells was inhibited in resistant PDAC cells. Our data show very inefficient attachment of VSV to the most resistant human PDAC cell line, HPAF-II. However, VSV attachment to HPAF-II cells was dramatically improved by treating cells with polycations. Moreover, combining VSV with polycations and ruxolitinib (which inhibits antiviral signaling) successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. We envision that this novel triple-combination approach could be used in the future to treat PDAC tumors that are highly resistant to OV therapy.


Quantitative and Atomic-Scale View of CO-Induced Pt Nanoparticle Surface Reconstruction at Saturation Coverage via DFT Calculations Coupled with in Situ TEM and IR.
Atomic-scale insights into how supported metal nanoparticles catalyze chemical reactions are critical for the optimization of chemical conversion processes. It is well-known that different geometric configurations of surface atoms on supported metal nanoparticles have different catalytic reactivity and that the adsorption of reactive species can cause reconstruction of metal surfaces. Thus, characterizing metallic surface structures under reaction conditions at atomic scale is critical for understanding reactivity. Elucidation of such insights on high surface area oxide supported metal nanoparticles has been limited by less than atomic resolution typically achieved by environmental transmission electron microscopy (TEM) when operated under realistic conditions and a lack of correlated experimental measurements providing quantitative information about the distribution of exposed surface atoms under relevant reaction conditions. We overcome these limitations by correlating density functional theory predictions of adsorbate-induced surface reconstruction visually with atom-resolved imaging by in situ TEM and quantitatively with sample-averaged measurements of surface atom configurations by in situ infrared spectroscopy all at identical saturation adsorbate coverage. This is demonstrated for platinum (Pt) nanoparticle surface reconstruction induced by CO adsorption at saturation coverage and elevated (>400 K) temperature, which is relevant for the CO oxidation reaction under cold-start conditions in the catalytic convertor. Through our correlated approach, it is observed that the truncated octahedron shape adopted by bare Pt nanoparticles undergoes a reversible, facet selective reconstruction due to saturation CO coverage, where {100} facets roughen into vicinal stepped high Miller index facets, while {111} facets remain intact.


Calcifying fibrous pseudotumor of the soft palate--a case report.
Calcifying fibrous pseudotumor has recently been described in the soft tissues. It is a rare benign lesion characterized by the presence of abundant hyalinized collagen with psammomatous or dystrophic calcification, and lymphoplasmacytic infiltrate. We report one such rare case in an 18 year old female with a nodular mass in the soft palate treated by complete resection. The mass had all the pathologic features of a calcifying fibrous pseudo-tumor.


Untreated Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): a case series.
Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is a rare inflammatory eye disease that affects the Retinal Pigment Epithelium and outer retina. The purpose of this study was to describe its presentations, as well as its prognosis in a series of untreated patients. Records of patients seen in the department of Ophthalmology at Cochin University Hospital, Paris, between April 2002 and June 2015 were retrospectively studied. Patients were included if they presented with the typical findings of APMPPE characterized by whitish or yellowish bilateral placoid lesions, a typical pattern of early hypofluorescence and late hyperfluorescence on fluorescein angiography. Only untreated patients who had been followed for at least 1 month were included. Out of 22 patients' records with a diagnosis of APMPPE, 10 patients (9 women, 1 man), with a mean age of 24.5 ± 4.2 years, fulfilled the study criteria with a diagnosis of typical untreated APMPPE. Prodromal symptoms were reported in 7/10 patients. Macular lesions were observed in 18/20 eyes. Sub-retinal fluid was seen at presentation in 3 eyes. Initial mean BCVA was 0.56 ± 0.81 LogMAR [- 0.10 to 2.30]. In 9 out of 10 cases, the time interval between manifestations in the first affected eye and the fellow eye was less than 3 days. After 1 month, BCVA had improved to 0.05 ± 0.089 LogMAR [0-0.3], with a decimal BCVA ≥0.8 in 17/20 eyes. In these 10 cases of untreated APMPPE, a favorable outcome was observed.


Epidemiology of Avian Infectious Bronchitis Virus Genotypes in Iran (2010-2014).
Infectious bronchitis virus (IBV) in vaccinated chicken flocks continues to cause enormous economic losses to the poultry industry in Iran. A molecular surveillance of IBV genotypes involved in outbreaks of disease was performed. Specimens of trachea, kidney, and cecal tonsil were collected from 250 suspected flocks (more than 2500 samples) and identified between 2010 and 2014. Partial spike glycoprotein gene sequences revealed seven distinct genotypes, including Mass, 793/B, IS720, Variant 2, QX, IR-I, and IR-II, to be circulating in the chicken farms. The majority of flocks (67.6%) experienced infection with an IBV variant unrelated to the vaccine strains. These variants displayed homologies ranging from 54.1% to 78.5% and from 53% to 86% with H120 and 4/91, respectively. These findings reveal the existence of IBV variants genetically different from the vaccine strains currently in use and explain the outbreaks of disease observed in the field. The current work constitutes the first comprehensive survey of IBV in Iran and emphasizes the need for continuous monitoring and rethinking of current preventative measures.


Risk factors for human immunodeficiency virus (HIV) infection among homosexual and bisexual men in a region at low risk for AIDS: the northeastern part of Italy. AIDS and Related Syndromes Study Group.
Prevalence and determinants of HIV infection were assessed in 127 homosexual and bisexual men in the northeastern part of Italy. The overall prevalence of HIV seropositivity was still rather low: 20% (95% confidence interval -CI- 13-27%). The most important risk factor for acquiring HIV infection turned out to be having has sexual intercourses in high-risk areas. Relative risks (RRs) for those who have travelled and had sex in North Europe and in the U.S., were, respectively, 2.7 (95% CI: 1.0-7.3) and 5.6 (95% CI: 1.2-25.9). A significantly increased risk was also seen for having a steady sexual partner (RR = 3.1, 95% CI: 1.3-7.5). Use of nitrite inhalants, high number of occasional sexual partners and habitual receptive anal intercourses were also associated with elevation of risk, whereas prostitution was not. The present study confirms the patterns of HIV spread among homosexual and bisexual men from high-risk areas to low-risk areas and prompts urgent educational intervention, in order to prevent the epidemics of AIDS among Italian homosexuals from reaching the size documented in other countries.


Refugees' Care Experiences, Self-Reported Health Outcomes and Transition to Mainstream Health Care After One Year at the Refugee Engagement and Community Health (REACH) Clinic.
This study reports how refugees experienced care at an integrated clinic during their first year in Canada and how they transitioned to a community physician. A survey was completed by 75 Government Assisted Refugees followed at the REACH clinic between 2018 and 2020; 16 agreed to an additional interview. Regression modelling explored the relationship between "perceived health status at one year" and several independent variables. Qualitative thematic analysis provided context. Tailored access to care and enhanced communication through interpretation contributed to satisfaction with clinic services. A significant positive relationship was found between their perceived health status and frequency of visits (p < 0.042), and "doctors' advice about how to stay healthy" (p < 0.039). Interview findings highlighted the important role of settlement agencies, timing for a successful transition and physicians' support resources. While refugees benefit from attending integrated clinics, these should also prepare the care transition to community physicians. Targeted government funding and continued medical education could enhance refugees' transition experience.


Bridging two worlds: Māori mental health nursing.
Building an Indigenous mental health workforce is a strategy used to develop culturally responsive and effective mental health services in New Zealand. However, researchers know little about Indigenous (Māori) mental health nursing. We undertook a Māori-centered methodology and grounded theory using focus groups to collect data from 10 Māori mental health nurses. We then analyzed the data using constant comparative analysis and theoretical sampling until saturation of the core category and subcategories emerged. "Bridging two worlds," together with two subcategories, "going beyond" and "practicing differently," explains the process Māori mental health nurses used to resolve the tensions they encountered working in the worlds of mainstream and Māori health services. This research provides insight into the tensions Indigenous and minority nurses experience when attempting to integrate cultural perspectives and practices to meet the needs of their patients.


Impact of Gut Recolonization on Liver Regeneration: Hepatic Matrisome Gene Expression after Partial Hepatectomy in Mice.
The hepatic matrisome is involved in the remodeling phase of liver regeneration. As the gut microbiota has been implicated in liver regeneration, we investigated its role in liver regeneration focusing on gene expression of the hepatic matrisome after partial hepatectomy (PHx) in germ-free (GF) mice, and in GF mice reconstituted with normal gut microbiota (XGF). Liver mass restoration, hepatocyte proliferation, and immune response were assessed following 70% PHx. Hepatic matrisome and collagen gene expression were also analyzed. Reduced liver weight/body weight ratio, mitotic count, and hepatocyte proliferative index at 72 h post PHx in GF mice were preceded by reduced expression of cytokine receptor genes Tnfrsf1a and Il6ra, and Hgf gene at 3 h post PHx. In XGF mice, these indices were significantly higher than in GF mice, and similar to that of control mice, indicating normal liver regeneration. Differentially expressed genes (DEGs) of the matrisome were lower in GF compared to XGF mice at both 3 h and 72 h post PHx. GF mice also demonstrated lower collagen expression, with significantly lower expression of Col1a1, Col1a2, Col5a1, and Col6a2 compared to WT mice at 72 h post PHx. In conclusion, enhanced liver regeneration and matrisome expression in XGF mice suggests that interaction of the gut microbiota and matrisome may play a significant role in the regulation of hepatic remodeling during the regenerative process.


Identification and seasonal distribution of airborne fungi in three horse stables in Italy.
Fungal agents are responsible for a variety of respiratory diseases both in humans and animals. The nature and seasonal variations of fungi have been investigated in many environments with wide ranging results. The aims of the present report were (i) to evaluate the quality and magnitude of exposure to airborne fungi in three differently structured equine stalls (open air, partially and completely enclosed buildings) during a one-year period, using an air sampling technique and (ii) to compare the distribution and frequency of fungal species, with regards to these different environments. Air samples were collected monthly from December 2001 to November 2002 by means of a surface air sampler (SAS) Super-90, (PBI International, Milan, Italy). Penicillium and Aspergillus spp. were cultured from all the stables in all seasons. Mucoraceae were also recovered in all seasons in stalls 1 and 2, while they were not isolated in spring and fall in stall 3. These fungi were detected in 28.4%, 72.9% and 60.5% of the total number of samples, respectively. Other fungal genera such as Alternaria, Cladosporium, Fusarium, Beauveria and Drechslera were also occasionally recovered. Viable fungal concentrations varied greatly, ranging from below the limit of detection to more than 3000 CFU/m3 for stables 1 and 2, and 1750 CFU/m3 for stable 3. The median fungal concentration was approximately 178 CFU/m3. Total fungal concentration appeared to be highest in summer, winter and spring, and lowest in the fall.


Bilateral pneumonia and inappropriate secretion of antidiuretic hormone in a premature infant.
A 6-week-old infant born prematurely had severe hyponatremia and other features of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This disturbance was believed to be secondary to extensive bilateral pneumonia with collapse of the right upper lobe. Although this association has been recognized in adults, this is the first report of its occurrence in an infant. SIADH must be considered in the differential diagnosis of hyponatremia in association with pneumonia in an infant.


Nanocomposites of C3N4 with Layers of MoS2 and Nitrogenated RGO, Obtained by Covalent Cross-Linking: Synthesis, Characterization, and HER Activity.
Generation of hydrogen by photochemical, electrochemical, and other means is a vital area of research today, and a variety of materials have been explored as catalysts for this purpose. C3N4, MoS2, and nitrogenated RGO (NRGO) are some of the important catalytic materials investigated for the hydrogen evolution reaction (HER) reaction, but the observed catalytic activities are somewhat marginal. Prompted by preliminary reports that covalent cross-linking of 2D materials to generate heteroassemblies or nanocomposites may have beneficial effect on the catalytic activity, we have synthesized nanocomposites wherein C3N4 is covalently bonded to MoS2 or NRGO nanosheets. The photochemical HER activity of the C3N4-MoS2 nanocomposite is found to be remarkable with an activity of 12778 μmol h-1 g-1 and a turnover frequency of 2.35 h-1. The physical mixture of C3N4 and MoS2, on the other hand, does not exhibit notable catalytic activity. Encouraged by this result, we have studied electrochemical HER activity of these composites as well. C3N4-MoS2 shows superior activity relative to a physical mixture of MoS2 and C3N4. Density functional theory calculations have been carried out to understand the HER activity of the nanocomposites. Charge-transfer between the components and greater planarity of cross-linked layers are important causes of the superior catalytic activity of the nanocomposites. Covalent linking of such 2D materials appears to be a worthwhile strategy for catalysis and other applications.


Improving Accuracy, Diversity, and Speed with Prime Macrocycle Conformational Sampling.
A novel method for exploring macrocycle conformational space, Prime macrocycle conformational sampling (Prime-MCS), is introduced and evaluated in the context of other available algorithms (Molecular Dynamics, LowModeMD in MOE, and MacroModel Baseline Search). The algorithms were benchmarked on a data set of 208 macrocycles which was curated for diversity from the Cambridge Structural Database, the Protein Data Bank, and the Biologically Interesting Molecule Reference Dictionary. The algorithms were evaluated in terms of accuracy (ability to reproduce the crystal structure), diversity (coverage of conformational space), and computational speed. Prime-MCS most reliably reproduced crystallographic structures for RMSD thresholds >1.0 Å, most often produced the most diverse conformational ensemble, and was most often the fastest algorithm. Detailed analysis and examination of both typical and outlier cases were performed to reveal characteristics, shortcomings, expected performance, and complementarity of the methods.


Collaborative learning in radiologic science education.
Radiologic science is a complex health profession, requiring the competent use of technology as well as the ability to function as part of a team, think critically, exercise independent judgment, solve problems creatively and communicate effectively. This article presents a review of literature in support of the relevance of collaborative learning to radiologic science education. In addition, strategies for effective design, facilitation and authentic assessment of activities are provided for educators wishing to incorporate collaborative techniques into their program curriculum. The connection between the benefits of collaborative learning and necessary workplace skills, particularly in the areas of critical thinking, creative problem solving and communication skills, suggests that collaborative learning techniques may be particularly useful in the education of future radiologic technologists. This article summarizes research identifying the benefits of collaborative learning for adult education and identifying the link between these benefits and the necessary characteristics of medical imaging technologists.


Effectiveness of virtual and augmented reality for improving knowledge and skills in medical students: protocol for a systematic review.
Virtual reality (VR) and augmented reality (AR) technologies are increasingly being used in undergraduate medical education. We aim to evaluate the effectiveness of VR and AR technologies for improving knowledge and skills in medical students. Using Best Evidence in Medical Education (BEME) collaboration guidelines, we will search MEDLINE (via PubMed), Education Resources Information Center, PsycINFO, Web of Knowledge, Embase and the Cochrane Central Register of Controlled Trials for English-language records, from January 1990 to March 2021. Randomised trials that studied the use of VR or AR devices for teaching medical students will be included. Studies that assessed other healthcare professionals, or did not have a comparator group, will be excluded. The primary outcome measures relate to medical students' knowledge and clinical skills. Two reviewers will independently screen studies and assess eligibility based on our prespecified eligibility criteria, and then extract data from each eligible study using a modified BEME coding form. Any disagreements will be resolved by discussion or, if necessary, the involvement of a third reviewer. The BEME Quality Indicators checklist and the Cochrane Risk of Bias Tool will be used to assess the quality of the body of evidence. Where data are of sufficient homogeneity, a meta-analysis using a random-effects model will be conducted. Otherwise, a narrative synthesis approach will be taken and studies will be evaluated based on Kirkpatrick's levels of educational outcomes and the Synthesis Without Meta-analysis guidelines. Ethical approval is not required for this systematic review as no primary data are being collected. We will disseminate the findings of this review through scientific conferences and through publication in a peer-reviewed journal.


Tert-butylamidinate tin(ii) complexes: high activity, single-site initiators for the controlled production of polylactide.
The tin(ii) coordination chemistry of two monoanionic N,N'-bis(2,6-diisopropylphenyl)alkylamidinate ligands is described. Complexation studies with the acetamidinate, [MeC(NAr)(2)](-), (Ar = 2,6-(i)Pr(2)C(6)H(3)) are complicated by the side formation of the bis(amidinate) tin(ii) compound, [MeC(NAr)(2)](2)Sn. By contrast, the bulkier tert-butylamidinate, [(t)BuC(NAr)(2)](-), allows tin(ii) mono-halide, -alkoxide and -amide complexes to be isolated cleanly in high yields. Thus, the reaction of [(t)BuC(NAr)(2)]H with (n)BuLi and subsequent treatment with SnCl(2) generates [(t)BuC(NAr)(2)]SnCl, in ca. 70% yield. Reactions of with LiO(i)Pr, LiNMe(2) and LiNTMS(2) afford [(t)BuC(NAr)(2)]Sn(O(i)Pr), [(t)BuC(NAr)(2)]Sn(NMe(2)), and [(t)BuC(NAr)(2)]Sn(NTMS(2)), respectively. The molecular structures of complexes are reported. Complexes, and have been investigated as initiators for the ring-opening polymerisation of rac-lactide: and display characteristics of well-controlled polymerisation initiators, but high molecular weight polymer is observed with due to inefficient initiation, a consequence of the steric bulk of the NTMS(2) unit. Polymerisations with and are faster than for the corresponding beta-diketiminate tin(ii) complexes, consistent with the more open nature of the tin(ii) coordination sphere.


A stirred bath technique for diffusivity measurements in cell matrices.
A stirred bath technique was developed for determining effective diffusivities in cell matrices. The technique involves cell immobilization in a dilute gel which has negligible effect on solute diffusion. Agar and collagen were tested as immobilizing gels. Agar gel was shown to have minor interactions with the diffusion of various biological molecules, and was used for immobilization of Ehrlich Ascites Tumor (EAT) cells. Diffusivities of glucose and lactic acid were measured in EAT matrices for cell loadings between 20 and 45 vol %. Treatment with glutaraldehyde was effective in quenching the metabolic activity of the cells while preserving their physical properties and diffusive resistance. The measured data agree favorably with predictions based on Maxwell's equation for effective diffusion in a periodic composite material. The stirred bath technique is useful for diffusivity determinations in immobilized matrices or free slurries, and is applicable to both microbial and mammalian cell systems.


Osteosarcoma progression is associated with increased nuclear levels and transcriptional activity of activated β-Catenin.
Osteosarcoma (OS) is an aggressive primary bone malignancy that has peak incidence in children and young adults <25 years of age. Despite current multimodal treatments, no significant change in patient outcome has been observed in two decades. Presently, there is a lack of established, reliable baseline prognostic markers for aggressive OS, other than extent and site of disease involvement. The canonical Wnt/β-catenin pathway controls multiple cellular processes, and is known to be a critical pathway in OS progression. This pathway regulates cellular levels of β-catenin, which is a significant player in the oncogenesis and progression of many cancers. We investigated the relationship between β-catenin, more specifically, the transcriptionally active form of β-catenin, Activated β-Catenin (ABC), and OS progression. Using an in vitro model, we observed that cellular/nuclear ABC levels, but not cellular/nuclear β-catenin levels, increase with the degree of aggressiveness in OS. Our results demonstrate a strong association between nuclear-ABC levels and aggressive OS in vitro. Furthermore, we observed significant correlation between positive nuclear-ABC and patient age and tumor stage. Our results support the potential use of ABC as a predictive marker for risk stratification in OS.


Novel neuropeptide Y receptor antagonists block vasoconstriction in the hamster cheek pouch microcirculation.
We investigated the efficacy of novel neuropeptide Y (NPY) antagonists to inhibit the microcirculatory dynamics of NPY in the hamster cheek pouch microcirculation using intravital microscopy and computer-assisted image analysis. Changes in arteriolar diameter served as an index of vasomotor alterations. Fluorescein isothiocyanate-labeled Dextran 150 served as a tracer for measurements of macromolecular transport. GW 383 and GW 1229, two novel NPY receptor antagonists, were applied topically in separate experiments. Pretreatment with 10(-5), 10(-6) and 10(-7) M GW 383 and with 10(-6) and 10(-8) M GW 1229 attenuated the vasoconstriction induced by 10(-7) M NPY in a dose-dependent manner. Furthermore, pretreatment with 10(-7) and 10(-8) M GW 1229 significantly inhibited the 10(-9) M NPY-induced vasoconstriction. At these doses, the NPY antagonists did not alter microvascular permeability. Our results demonstrate that the novel NPY antagonists inhibit the vasoconstriction induced by NPY in the hamster check pouch microcirculation. We suggest that the inhibition is due to binding of antagonists to Y1-type NPY receptors.


Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy: a preliminary study of ten patients.
After a brain biopsy, the genetic analysis can fail because of insufficient material, extensive tumor necrosis, and formalin fixation under conditions that adversely affected the quality of the DNA or because the assay result was indeterminant. The freezing of fresh tumor tissue at surgery could greatly improve the success of DNA extraction and methyl guanine methyl transferase (MGMT) promoter methylation testing. The concentration of the DNA samples can also be improved from a withdrawal in an area with a high probability of neoplastic cells. The present study reports the results of ten frameless image-guided intracranial needle biopsies from April 2008 until February 2009, among a total of 28 frameless neuronavigation brain biopsy performed from May 2007 to February 2009. The protocol sampling provided withdrawal specimens correlated with neuroimaging characteristics of the lesions. The molecular determination of MGMT promoter was assessed with the nested methylation-specific polymerase chain reaction on fresh or cryopreserved needle bioptic tissue. The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in six patients, including a brain infection. The image-guided trajectory of the biopsy and the intraoperative frozen section increased the diagnostic yield. To the best of the authors' knowledge, this is the first report with the MGMT promoter status analysis on needle bioptic fresh tissue. In the future, the availability of the molecular genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment.


Bioinformatics Analysis of circRNA Expression and Construction of "circRNA-miRNA-mRNA" Competing Endogenous RNAs Networks in Bipolar Disorder Patients.
Bipolar disorder (BD) is a severe mood disorder disease in China, and its underlying pathogenesis remains unknown. Circular RNAs (circRNAs) have been reported to play a key role in mental disorders and can be used as competitive endogenous RNAs (ceRNAs). However, little is known about the correlation of circRNAs with BD. In this study, Deep RNA sequencing was used to identify differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs) between BD patients and a control group. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed RNAs (DE-RNAs). In all 9,593 circRNAs and 20,030 mRNAs were found in the two groups of specimens, among which 50 DE-circRNAs and 244 DE-mRNAs were significantly upregulated, and 44 DE-circRNAs and 294 DE-mRNAs were significantly downregulated. Based on the regulatory mechanism of ceRNAs, circRNAs can directly bind microRNAs (miRNAs) to affect mRNA expression, and the expression trends of circRNAs and mRNAs are consistent. According to this mechanism, we constructed two ceRNA networks by using the RNA sequencing data. The function of these DE-circRNAs was further elucidated by enrichment analysis. In summary, the present study showed that the circRNA expression profile of BD patients is altered, and a ceRNA regulatory network was constructed, which provided a hypothesis about the pathogenesis of BD.


Student views on the introduction of anatomy teaching packages into clinical attachments.
Following the implementation of the GMC document Tomorrow's Doctors in 1993 the amount of time dedicated to anatomy in undergraduate curricula has been reduced. This has resulted in considerable disquiet among physicians and surgeons with regard to the anatomical knowledge of newly qualified doctors, and also amongst students. This study aimed to assess the perceived student need for anatomical teaching packages to support clinical attachments in the later years of the undergraduate medical curriculum. The views of two groups of students were obtained: Group A were at the beginning of their clinical attachments, whereas Group B had completed all clinical attachments and had sat the final examination. The majority of students indicated that there was a need for the development of a teaching package for anatomy (and other basic sciences) in the later stages of the undergraduate medical curriculum. A high proportion stated that the completion of these packages should be in a self-directed manner with a staff member available. There was a difference between both groups in response to the best time to offer the packages, and in the clinical areas which might be prioritized in such a development. We conclude that the vertical integration of anatomy--perhaps through clinically focused teaching packages--would be welcomed by students as part of their clinical attachments.


Validity and reliability of the school function assessment in elementary school students with disabilities.
This study examined validity of the School Function Assessment (SFA) and interrater reliability of occupational therapist and teacher ratings of students' school function. The validity of the SFA was examined using the known-group method in 35 participants in kindergarten through 7th grade attending elementary schools; 15 students with learning disabilities (LD), 11 students with autism, and 9 students with traumatic brain injury (TBI). The SFA criterion scores for the 23 individual scales were clustered into five distinct parts for the validity analyses. Significant differences in SFA scores among the 3 groups of students were found using Kruskal-Wallis analyses (Chi2 ranged from 9.28 to 20.55, p <.01). Two discriminant analyses demonstrated high correct classification of students with autism and LD, but showed less accurate classification of students with TBI, indicating that the SFA scores of students with TBI did not fall into a systematic pattern for classification. For the interrater reliability study, 16 students' ratings by their teacher and occupational therapist were analyzed. Intraclass correlations resulted in moderate relationships between teacher and occupational therapist ratings for the average criterion scores for the three main sections of the SFA: participation,.70; task supports,.68; and activity performance,.73. Results of this study are discussed in terms of validity of score interpretation and the reliability of different team members completing the SFA questionnaire.


Dose-dependent protective effect of sildenafil citrate on testicular injury after torsion/detorsion in rats.
This experiment was designed to investigate the effect of sildenafil citrate on testicular injury after unilateral testicular torsion/detorsion (T/D). Thirty-seven adult male Wistar albino rats were divided into four groups: sham operated group (group 1), T/D+ saline (group 2), T/D+ 0.7 mg sildenafil citrate (group 3) and T/D+ 1.4 mg sildenafil citrate (group 4). Testicular torsion was created by rotating the right testis 720° in a clockwise direction for 2 h in other groups, except for group 1, which was served as sham group. The level of GSH (P < 0.05) in the testis in the group 2 were significantly lower (P < 0.05) and the levels of MDA and NO (P < 0.01 for both) in the testis were significantly higher when compared with those of the group 1. Administration of low dose sildenafil citrate prevented the increases in MDA and NO levels and decreases in GSH values induced by testicular torsion. However, administration of high dose sildenafil citrate did not have any effect on these testicular tissue parameters (P > 0.05). Also, mean values of seminiferous tubules diameters, germinal cell layer thicknesses and mean testicular biopsy score were significantly better in group 3 than groups 2 and 4. These results suggest that T/D injury occurred in testis after unilateral testicular T/D and that administration of low dose sildenafil citrate before detorsion prevents ischemia/reperfusion cellular damage in testicular torsion. Sildenafil citrate probably acts through reduction of reactive oxygen species and support antioxidant enzyme systems.


The AMH genotype (rs10407022 T>G) is associated with circulating AMH levels in boys, but not in girls.
Fetal anti-Müllerian hormone (AMH) is responsible for normal male sexual differentiation, and circulating AMH is used as a marker of testicular tissue in newborns with disorders of sex development. Little is known about the mechanism of action in postnatal life. A recent genome wide association study (GWAS) reported genetic variation of AMH affecting AMH levels in young men. This study investigated the effect of genetic variation of AMH and AMH type II receptor (AMHR2) (AMHrs10407022 T>G and AMHR2rs11170547 C>T) on circulating reproductive hormone levels and pubertal onset in boys and girls. This study is a combined longitudinal and cross-sectional study in healthy Danish boys and girls from the general population. We included 658 boys aged 5.8-19.8 years and 320 girls aged 5.6-16.5 years. The main outcome measures were genotyping of AMH and AMHR2, pubertal staging and serum levels of reproductive hormones. AMHrs10407022T>G was associated with higher serum levels of AMH in prepubertal boys (TT: 575 pmol/L vs TG: 633 pmol/L vs GG: 837 pmol/L, P = 0.002) and adolescents (TT: 44 pmol/L vs TG: 58 pmol/L vs GG: 79 pmol/L, P < 0.001). Adolescent boys carrying the genetic variation also had lower levels of LH (TT: 3.0 IU/L vs TG: 2.8 IU/L vs GG: 1.8 IU/L, P = 0.012). Hormone levels in girls and pubertal onset in either sex did not seem to be profoundly affected by the genotypes. Our findings support recent GWAS results in young adults and expand our understanding of genetic variation affecting AMH levels even in boys prior to the pubertal decline of circulating AMH.


Solvent-free atom transfer radical polymerization for the preparation of poly(poly(ethyleneglycol) monomethacrylate)-grafted Fe3O4 nanoparticles: synthesis, characterization and cellular uptake.
Poly(poly(ethyleneglycol) monomethacrylate) (P(PEGMA))-grafted magnetic nanoparticles (MNPs) were successfully prepared via a solvent-free atom transfer radical polymerization (ATRP) method. The macroinitiators were immobilized on the surface of 6.4+/-0.8 nm Fe(3)O(4) nanoparticles via effective ligand exchange of oleic acid with 3-chloropropionic acid (CPA), which rendered the nanoparticles soluble in the PEGMA monomer. The so-obtained P(PEGMA)-grafted MNPs have a uniform hydrodynamic particle size of 36.0+/-1.2 nm. The successful grafting of P(PEGMA) on the MNP surface was ascertained from FTIR and XPS analyses. The uptake of the MNPs by macrophage cells is reduced by two-orders of magnitude to <2 pg Fe/cell after surface grafting with P(PEGMA). Furthermore, the morphology and viability of the macrophage cells cultured in a medium containing 0.2 mg/mL of P(PEGMA)-grafted MNPs were found similar to those of cells cultured without nanoparticles, indicating an absence of significant cytotoxicity effects. T(2)-weighted magnetic resonance imaging (MRI) of P(PEGMA)-grafted MNPs showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water. The R(1) and R(2) values per millimole Fe, and R(2)/R(1) value of the P(PEGMA)-grafted MNPs were calculated to be 8.8 mm(-1)s(-1), 140 mm(-1)s(-1), and 16, respectively. These results indicate that the P(PEGMA)-grafted MNPs have great potential for application in MRI of specific biotargets.


Detection of prostate cancer with MR spectroscopic imaging: an expanded paradigm incorporating polyamines.
To characterize benign and malignant prostate peripheral zone (PZ) tissue retrospectively by using a commercial magnetic resonance (MR) spectroscopic imaging package and incorporating the choline plus creatine-to-citrate ratio ([Cho + Cr]/Cit) and polyamine (PA) information into a statistically based voxel classification procedure. The institutional review board approved this HIPAA-compliant study and waived the requirement for informed consent. Fifty men (median age, 60 years; range, 44-69 years) with untreated biopsy-proved prostate cancer underwent combined endorectal MR imaging and MR spectroscopic imaging. Commercial software was used to acquire and process MR spectroscopic imaging data. The (Cho + Cr)/Cit and the PA level were tabulated for each voxel. The PA level was scored on a scale of 0 (PA undetectable) to 2 (PA peak as high as or higher than Cho peak). Whole-mount step-section histopathologic analysis constituted the reference standard. Classification and regression tree analysis in a training set generated a decision-making tree (rule) for classifying voxels as malignant or benign, which was validated in a test set. Receiver operating characteristic and generalized estimating equation regression analyses were used to assess accuracy and sensitivity, respectively. The median (Cho + Cr)/Cit was 0.55 (mean +/- standard deviation, 0.59 +/- 0.03) in benign and 0.77 (mean, 1.08 +/- 0.20) in malignant PZ voxels (P = .027). A significantly higher percentage of benign (compared with malignant) voxels had higher PA than choline peaks (P < .001). In the 24-patient training set (584 voxels), the rule yielded 54% sensitivity and 91% specificity for cancer detection; in the 26-patient test set (667 voxels), it yielded 42% sensitivity and 85% specificity. The percentage of cancer in the voxel at histopathologic analysis correlated positively (P < .001) with the sensitivity of the classification and regression tree rule, which was 75% in voxels with more than 90% malignancy. The statistically based classification rule developed indicated that PAs have an important role in the detection of PZ prostate cancer. With commercial software, this method can be applied in clinical settings.


Procaine Inhibits Proliferation and Migration and Promotes Cell Apoptosis in Osteosarcoma Cells by Upregulation of MicroRNA-133b.
Procaine (PCA) is a conventional chemotherapeutic agent for osteosarcoma. Recent studies have proposed that the growth-inhibitory effect of PCA is through regulation of microRNAs (miRNAs). miR-133b has been proven to be a tumor suppressor in osteosarcoma, but whether it is involved in the antitumor effects of PCA on osteosarcoma has not been investigated. In this study, we aimed to explore the effects of PCA on osteosarcoma MG63 cells by regulation of miR-133b, as well as its underlying mechanisms. MG63 cells were treated with different concentrations of PCA, and cell viability, apoptosis, and miR-133b expression were then detected by MTT, flow cytometry, and qRT-PCR, respectively. Cells were then transfected with the miR-133b inhibitor and treated with 2 μM PCA. Thereafter, cell viability, migration, and apoptosis were detected. Analysis of signaling pathways was detected by Western blot. Our results showed that PCA significantly inhibited cell viability and promoted apoptosis and the expression level of miR-133b in a dose-dependent manner (p < 0.05 or p < 0.01). Moreover, we observed that PCA + miR-133b inhibitor dramatically reversed the effects of PCA on cell viability, apoptosis, and migration (p < 0.05 or p < 0.01). In addition, PCA significantly decreased the levels of p/t-AKT (p308 or p473), p/t-ERK, and p/t-S6, whereas PCA + miR-133b inhibitor rescued these effects. Our results suggest that PCA inhibits proliferation and migration but promotes apoptosis in osteosarcoma cells by upregulation of miR-133b. These effects may be achieved by inactivation of the AKT/ERK pathways.


Comparison of Flea (Siphonaptera) Burdens on the Endangered San Joaquin Kit Fox (Vulpes macrotis mutica (Carnivora, Canidae)) Inhabiting Urban and Nonurban Environments in Central Valley, California.
The San Joaquin kit fox (Vulpes macrotis mutica Merriam (Carnivora, Canidae)) is an endangered small carnivore endemic to the San Joaquin Valley of California. Commercial and agricultural land expansion has contributed to the species' decline and invasion of more cosmopolitan species, providing means for potential ecological shifts in disease vector and host species. Fleas are common ectoparasites that can serve as important indicators of cross-species interactions and disease risk. We compared flea load and species composition on kit foxes inhabiting urban and nonurban habitats to determine how urbanization affects flea diversity and potential disease spillover from co-occurring species. We identified Echidnophaga gallinacea (Westwood) (Siphonaptera, Pulicidae) and Pulex spp. (L.) in both urban and nonurban populations, and Ctenocephalides felis (Bouche) (Siphonaptera, Pulicidae) only in the urban population. Flea load scores differed significantly across capture sites and with respect to concomitant sarcoptic mange infestation in the urban population, with milder flea infestations more typical of healthy foxes. All observed flea species are known vectors for pathogens that have been detected in mesocarnivores. Further examination of kit fox fleas and their associated pathogens will help to direct conservation and disease preventive measures for both wildlife and humans in the region.


Epidemiology of bronchial asthma and asthma control assessment in Henan Province, China.
Prevalence of bronchial asthma, asthma treatment assessment, and estimation of the control level among asthma patients in Henan Province, China are reported in this paper. We selected 10 among the 109 cities and districts in Henan province using a multistage stratified cluster random sampling method. A total of 500 households from each city and district were chosen. Approximately 20,000 residents from a total of 5,000 households were randomly selected to answer a questionnaire recommended by the China Asthma Alliance. Asthma patients were asked to answer a detailed questionnaire using the symptom-based guidelines to assess the levels of disease control. The overall prevalence of asthma was 0.73% ± 0.12%. Urban and rural residents had asthma prevalence rates of 1.1% ± 0.23% (88/7,924) and 0.48% ± 0.12% (57/11,792), respectively. Among the asthma patients, only 33.8% (52) received regular medication, 25% (13) used oral glucocorticoids, and 71.1% (37) used oral theophylline. The classified control levels of patients were as follows: 33.1% controlled, 49.7% partially controlled, and 17.2% uncontrolled. A total of 38.5% and 27.5% of regularly and irregularly treated asthma patients reached controlled level, respectively. The two groups significantly differed in asthma control level. Asthma prevalence is low in Henan Province, China. Urban residents have higher prevalence of asthma than rural residents do. Patients with asthma receive insufficient medication, resulting in suboptimal asthma control. Improvement in diagnosis and treatment of asthma patients is urgently needed.


In Situ Continuous Measurement of Salinity in Estuarine and Coastal Sediments by All-Solid Potentiometric Sensors.
Salinity is crucial for understanding the environmental and ecological processes in estuarine and coastal sediments. In situ measurements in sediments are scarce due to the low water content and particulate adsorption. Here, a new potentiometric sensor principle is proposed for the real-time in situ measurement of salinity in sediments. The sensor system is based on paper sampling and two all-solid electrodes, a cation-selective electrode (copper hexacyanoferrate, CuHCF) and an anion-selective electrode (Ag/AgCl). The spontaneous aqueous electrolyte extraction and redox reaction can produce a Nernstian response on both electrodes that is directly related to salinity. This potentiometric sensor allows for salinity acquisition in a wide salinity range (1-50 ppt), with high resolution (<1 ppt), and at a low water content (<30%), and it has been applied for the in situ measurement of salinity and the interpretation of cycling processes of metals in estuarine and coastal sediments. Moreover, the sensor coupled to a wireless monitoring system exhibited remote-sensing capability and successfully captured the salinity dynamic processes of the overlying water and pore water during the tidal period. This sensor with its low cost, versatility, and applicability represents a valuable tool to advance the comprehension of salinity and the salinity-driven dissolved-matter variations in estuarine and coastal sediments.


Essential oils encapsulated in liposomes: a review.
In the recent years there has been an increased interest toward the biological activities of essential oils. However, essential oils are unstable and susceptible to degradation in the presence of oxygen, light and temperature. So, attempts have been made to preserve them through encapsulation in various colloidal systems such as microcapsules, microspheres, nanoemulsions and liposomes. This review focuses specifically on encapsulation of essential oils into liposomes. First, we present the techniques used to prepare liposomes encapsulating essential oils. The effects of essential oils and other factors on liposome characteristics such as size, encapsulation efficiency and thermal behavior of lipid bilayers are then discussed. The composition of lipid vesicles membrane, especially the type of phospholipids, cholesterol content, the molar ratio of essential oils to lipids, the preparation method and the kind of essential oil may affect the liposome size and the encapsulation efficiency. Several essential oils can decrease the size of liposomes, homogenize the liposomal dispersions, increase the fluidity and reduce the oxidation of the lipid bilayer. Moreover, liposomes can protect the fluidity of essential oils and are stable at 4-5 °C for 6 months at least. The applications of liposomes incorporating essential oils are also summarized in this review. Liposomes encapsulating essential oils are promising agents that can be used to increase the anti-microbial activity of the essential oils, to study the effect of essential oils on cell membranes, and to provide alternative therapeutic agents to treat several diseases.


Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study.
The effect of early initiation of auranofin (AF) therapy on outcome measures was studied in a controlled 24-month double blind trial in 138 patients with early rheumatoid arthritis (RA) using an intent to treat approach. Patients were randomized to AF or placebo but in case of insufficient effect or intolerable adverse events, they switched to open disease modifying antirheumatic drug therapy. Patients who started AF fared significantly better in improved joint swelling. Stanford Health Assessment Questionnaire index, Keitel functional test, and mental depression, and furthermore, radiologic progression was significantly retarded. Our results support a disease modifying beneficial effect of AF in early active RA.se


Innovative techniques in bony reconstruction to facilitate hand salvage.
Mutilating injuries of the hand and congenital hand anomalies can present challenging reconstructive scenarios for salvage and restoration of function. During a 5-year period from 1993 to 1997, the plastic and reconstructive surgical unit of East Carolina University Medical Center was presented with a series of unique reconstructive challenges as a result of complex hand injuries that resulted in unexpected opportunities for the salvage of distal components. These traumatic injuries were unique in that, although devastating to the hand, they left the opportunity for salvage of distal vascularized and sensate components of the hand. Other unique challenges arose as a result of patients who did not want to pursue alternative reconstructive options such as toe-to-hand transfers or pollicization. These cases are presented to emphasize alternative algorithms to standard hand reconstruction in complex scenarios. Three patients presented with distal viable (vascularized and sensate) phalangeal components with proximal complex bony defects, 1 patient presented with a complex thumb defect and declined standard therapy, and 1 patient presented with a congenital thumb anomaly and declined standard therapy. All flaps survived and all hands were saved. These patients illustrate the clinical feasibility of osteocutaneous and free osseous grafting to provide strut stabilization in metacarpal defects and to preserve an opposable post after thumb amputation or thumb anomaly.


Long-term benzodiazepine use and cognitive decline in the elderly: the Epidemiology of Vascular Aging Study.
Several cross-sectional studies have found cognitive impairment in subjects taking benzodiazepines for long periods. However, it is not known whether long-term use of benzodiazepines accelerates cognitive decline in the elderly. The authors addressed this issue in a follow-up study of 1,389 people aged 60 to 70 years recruited from the electoral rolls of the city of Nantes (Epidemiology of Vascular Aging study). Data on cognitive functioning (five cognitive tests), depressive symptoms (Center for Epidemiologic Studies-Depression Scale), anxiety symptoms (Spielberger Inventory Scale), use of psychotropics and other drugs, and tobacco and alcohol consumption were collected at baseline, 2-year, and 4-year examinations. People reporting to take benzodiazepines at one, two and three examinations were classified as episodic, recurrent, and chronic users, respectively. Among the 1,176 subjects (85%) who participated in the three examinations, the proportions of episodic, recurrent, and chronic users were 10%, 6%, and 7%, respectively. Chronic users of benzodiazepines had a significantly higher risk of cognitive decline in the global cognitive test (Mini Mental State Examination) and the two attention tests than nonusers (Mini Mental State Examination: odds ratio [OR] [95% confidence interval (CI)] = 1.9 [1.0-3.5]; Digit Symbol Substitution test: OR [95% CI] = 2.7 [1.6-4.7]; Trail Making test, part B: OR [95% CI] = 2.1 [1.2-3.7]). Overall, episodic and recurrent users had lower cognitive scores than nonusers, but differences were not statistically significant. These results were independent of age, sex, education, alcohol and tobacco use, anxiety and depression scores, and use of psychotropic drugs other than benzodiazepines. The findings suggest that long-term use of benzodiazepines is risk factor of increased cognitive decline in the elderly.


A new characterization of the Euclidean sphere.
In this paper, we obtain a new characterization of the Euclidean sphere as a compact Riemannian manifold with constant scalar curvature carrying a nontrivial conformal vector field which is also conformal Ricci vector field.


Regulation of endogenous dopamine release in amphibian retina by gamma-aminobutyric acid and glycine.
Endogenous dopamine release in the retina of the African clawed frog (Xenopus laevis) increases in light and decreases in darkness. The roles of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and glycine in regulating this light/dark difference in dopamine release were explored in the present study. Exogenous GABA, the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, and the GABA-C receptor agonist cis-aminocrotonic acid (CACA) suppressed light-evoked dopamine overflow from eyecups. The effects of GABA-A and -B receptor agonists were selectively reversed by their respective receptor-specific antagonists, whereas the effect of CACA was reversed by the competitive GABA-A receptor antagonist bicuculline. The benzodiazepine diazepam enhanced the effect of muscimol on light-evoked dopamine release. Both GABA-A and -B receptor antagonists stimulated dopamine release in light or darkness. Bicuculline was more potent in light than in darkness. These data suggest that retinal dopaminergic neurons are inhibited by GABA-A and -B receptor activation in both light and darkness but that GABA-mediated inhibitory tone may be greater in darkness than in light. Exogenous glycine inhibited light-stimulated dopamine release in a concentration-dependent and strychnine-sensitive manner. However, strychnine alone did not increase dopamine release in light or darkness, nor did it augment bicuculline-stimulated release in darkness. Additionally, both strychnine and 7-chlorokynurenate, an antagonist of the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate subtype of glutamate receptor, suppressed light-evoked dopamine release. Thus, the role of endogenous glycine in the regulation of dopamine release remains unclear.


[Users of ultrasound machines are often subjected to musculoskeletal could be preventive measures. Better work organization and equipment could be preventive measures].
Stress, musculoskeletal symptoms, and eye strain are common among users of ultrasound machines. The purpose of the study was to identify work situations that induce a psychosocial or physical load in work with ultrasound. 12 sonographers participated. Questionnaire and video-based interviewing methods were used. Effects of changes in work organisation and equipment that were introduced after the first study were followed up after 6 months (9 of the participants in the former study). The study confirmed that musculoskeletal symptoms were common. Work situations inducing physical and/or psychosocial loads were identified. Changes of the equipment and work organisation led to positive effects both in terms of the physical and the psychosocial load. Better work organisation and ergonomically designed equipment are measures that can prevent work-related disorders.


Conformational and stereochemical flexibility in cadmium(II) complexes of aza-thioether macrocycles.
The synthesis and crystal structures of four CdII macrocyclic complexes containing mixed N-, O- and S-donors, [Cd(NO3)2([12]aneN2S2)] (1), [Cd(NO3)2([12]aneNS3)] (2), [Cd(NO3)2([15]aneNO2S2)] (3) and [Cd(NO3)([15]aneN2O2S)]NO3 (4), are presented. The metal ion is coordinated outside of the macrocyclic cavity in the complexes of the smaller macrocycles ([12]aneN2S2 and [12]aneNS3) while the flexibility of the larger macrocycles in and allows very different conformations to be adopted with a 'butterfly' geometry in and a flattened geometry in. No correlation between the number of sulfur donors and Cd-S bond distance in these types of complexes is observed, although the number and binding mode of the nitrato ligands is determined by the conformation and binding mode of the macrocycle. The position of the nitrato ligand also influences, through steric conflicts with the macrocyclic donor atoms, the bond distances in both ligand systems.


[Obstructif sleep apnea-hypopnea syndrome: evolution of an old concept].
This review summarizes the well-known clinical features of the obstructive sleep apnea-hypopnea syndrome (OSAHS) and emphasizes new research on this syndrome. Though described in the seventies, the prevalence OSAHS is known mainly in the US. A dramatic increasing in prevalence has been related to the increase prevalence of obesity, raising a substantial public health problem. Discussion continues on the proper definition of the syndrome and degrees of severity. Multiple factors are involved in the pathogenesis of sleep apnea: anatomic abnormalities, mechanical factors, nervous alterations, muscular imbalance between pharyngeal constrictor and dilator muscles or part of a metabolic syndrome? Indeed, obstructive sleep apnea with and without obesity is increasingly implicated in the initiation and progression of metabolic disorders and of cardiovascular diseases (hypertension, cardiac ischemia and probably congestive heart failure, cardiac arrhythmias and strokes). An extended literature reports the neural, humoral, thrombotic, metabolic and inflammatory mechanisms linking OSAHS to endocrinology and cardiovascular diseases. Daytime sleepiness, cognitive, memory and performance deficits with their risks are also stressed. These consequences require treating this syndrome as soon as possible. Multiple interventions (medical, mechanical-nasal positive airway pressure or oral appliances, and sometimes surgical management) can be used but nasal continuous positive airway pressure is the "gold standard" treatment in severe OSAHS. More often multiple interventions are appropriate in a given patient. Finally, there is growing evidence that genetic factors influence the expression of OSAHS. Numerous genetic studies have investigated the etiology of OSAHS with the goal of improving our understanding of its pathogenesis.


Compatible and Incompatible Mycorrhizal Fungi With Seeds of Dendrobium Species: The Colonization Process and Effects of Coculture on Germination and Seedling Development.
Orchids highly rely on mycorrhizal fungi for seed germination, and compatible fungi could effectively promote germination up to seedlings, while incompatible fungi may stimulate germination but do not support subsequent seedling development. In this study, we compared the fungal colonization process among two compatible and two incompatible fungi during seed germination of Dendrobium officinale. The two compatible fungi, i.e., Tulasnella SSCDO-5 and Sebacinales LQ, originally from different habitats, could persistently colonize seeds and form a large number of pelotons continuously in the basal cells, and both fungi promoted seed germination up to seedling with relative effectiveness. In contrast, the two incompatible fungi, i.e., Tulasnella FDd1 and Tulasnella AgP-1, could not persistently colonize seeds. No pelotons in the FDd1 treatment and only a few pelotons in the AgP-1 treatment were observed; moreover, no seedlings were developed at 120 days after incubation in either incompatible fungal treatment. The pattern of fungal hyphae colonizing seeds was well-matched with the morphological differentiation of seed germination and seedling development. In the fungal cocultural experiments, for both orchids of D. officinale and Dendrobium devonianum, cocultures had slightly negative effects on seed germination, protocorm formation, and seedling formation compared with the monocultures with compatible fungus. These results provide us with a better understanding of orchid mycorrhizal interactions; therefore, for orchid conservation based on symbiotic seed germination, it is recommended that a single, compatible, and ecological/habitat-specific fungus can be utilized for seed germination.


Twelve-Week Treatment With Liraglutide as Add-on to Insulin in Normal-Weight Patients With Poorly Controlled Type 1 Diabetes: A Randomized, Placebo-Controlled, Double-Blind Parallel Study.
This study investigated the efficacy and safety of once-daily liraglutide 1.2 mg versus placebo as add-on to insulin treatment in normal-weight patients with poorly controlled type 1 diabetes. In a randomized (1:1), double-blind, placebo-controlled design, 40 patients with type 1 diabetes (HbA1c ≥8% [64 mmol/mol]) received once-daily liraglutide 1.2 mg or placebo for 12 weeks. Continuous glucose monitoring was performed before and at the end of treatment. The primary end point was change in HbA1c. Secondary end points included change in insulin dose, weight, glycemic excursions, heart rate, and blood pressure. Baseline HbA1c was similar in the liraglutide and placebo group (8.8 ± 0.2 and 8.7 ± 0.1% [72.5 ± 2.2 and 71.8 ± 1.5 mmol/mol]). Change in HbA1c from baseline was -0.6 ± 0.2% (-6.22 ± 1.71 mmol/mol) with liraglutide and -0.5 ± 0.2% (-5.56 ± 1.67 mmol/mol) with placebo (P = 0.62). Variation in glycemic excursions did not change in either group. Change in body weight was -3.13 ± 0.58 and +1.12 ± 0.42 kg (P < 0.0001) with liraglutide and placebo, respectively. The bolus insulin dose decreased in liraglutide-treated patients and did not change with placebo treatment (4.0 ± 1.3 vs. 0.0 ± 1.0 IU, P = 0.02). Heart rate increased within the liraglutide group (P = 0.04) but not compared with placebo, whereas mean systolic blood pressure decreased compared with placebo (between-group difference 3.21 mmHg [95% CI -8.31 to 1.90], P = 0.04). Liraglutide was more frequently associated with gastrointestinal adverse effects. The incidence of hypoglycemia did not differ between groups. Liraglutide significantly reduces body weight and insulin requirements but has no additional effect on HbA1c in normal-weight patients with type 1 diabetes inadequately controlled on insulin alone.


Global metabolomic profiling of acute myocarditis caused by Trypanosoma cruzi infection.
Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.


Allogeneic bone marrow transplantation for leukemia: factors of importance for long-term survival and relapse.
From 1977 until June 1987, 139 patients with leukemia underwent allogeneic bone marrow transplantation at Huddinge Hospital. Among recipients of HLA identical bone marrow the survival plateau for 30 patients with acute myeloid leukemia in first remission was 71% from 3 to 7 years. Children (n = 11) had a survival of 100% compared with 52% (n = 19) in adults (p = 0.01). Among patients with acute lymphoblastic leukemia in first remission (n = 15) the actuarial 5-year survival was 73% compared with 31% for those (n = 25) in second to fourth remissions. The probability of relapse in these two groups was 9% and 45% respectively (p less than 0.05). Patients with chronic myeloid leukemia in first chronic phase (n = 27) had a survival plateau from 1 to 6 years of 65%. In Cox's multivariate regression analysis, improved survival was associated with grade 0-I acute graft-versus-host disease (GVHD) (p less than 0.0001), HLA-matched siblings (p less than 0.001), recipient age less than 17 years (p = 0.02), first remission and first chronic phase (p = 0.03), cytomegalovirus (CMV) seronegative recipients (p = 0.04) and absence of symptomatic CMV infection (p = 0.04). A decreased risk of relapse was seen in patients with first remission or first chronic phase (p less than 0.001) and in patients with asymptomatic CMV infection (p = 0.03). In multivariate analysis the p values were 0.002 and 0.09 for these two groups respectively. In these patients acute GVHD was the major obstacle to successful outcome.


Choice of surveillance after hepatectomy for colorectal metastases.
By review of a reported series, is outcome related to surveillance after hepatectomy? We reviewed English-language literature indexed on MEDLINE from January 1, 1990, through December 31, 2002. Indexing terms were combinations of hepatectomy, colorectal metastases, and recurrence with prognostic, repeat, follow-up, or surveillance. Studies containing any of the following data fields were included: recurrence after hepatectomy, rates of repeat hepatectomy, 5-year survival (overall or disease free) after hepatectomy (initial or repeat), posthepatectomy surveillance protocol, and detection of recurrence by surveillance modality. Data were taken directly from a small number of articles and pooled across studies for analysis. We highlighted difficulties in assessing data quality and validity as a caveat to the interpretation of the results. The rate of recurrence after hepatectomy was 58%, and the rate of hepatic recurrence was 30%. Repeat hepatectomy was performed in 9.6% of cases. Five-year survivals after initial and repeat hepatectomy were 29% and 38%, respectively. Many studies did not report their surveillance protocols. For those that did, computed tomography or ultrasonography with carcinoembryonic antigen measurement most commonly formed the basis of surveillance. No data related surveillance techniques to the outcomes of recurrence detection, repeat hepatectomy, or survival. This review confirmed the value of repeat hepatectomy for recurrent disease, but uncovered no direct evidence supporting any surveillance modalities. Further studies are clearly needed, and approaches to these are discussed.


Effect of limestone particle size and calcium to non-phytate phosphorus ratio on true ileal calcium digestibility of limestone for broiler chickens.
The purpose of this study was to determine the effect of limestone particle size and calcium (Ca) to non-phytate phosphorus (P) ratio on the true ileal Ca digestibility of limestone for broiler chickens. A limestone sample was passed through a set of sieves and separated into fine (<0.5 mm) and coarse (1-2 mm) particles. The analysed Ca concentration of both particle sizes was similar (420 g/kg). Six experimental diets were developed using each particle size with Ca:non-phytate P ratios of 1.5:1, 2.0:1 and 2.5:1, with ratios being adjusted by manipulating the dietary Ca concentrations. A Ca-free diet was also developed to determine the basal ileal endogenous Ca losses. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to 6 replicate cages (8 birds per cage) and fed from d 21 to 24 post hatch. Apparent ileal digestibility of Ca was calculated using the indicator method and corrected for basal endogenous losses to determine the true Ca digestibility. The basal ileal endogenous Ca losses were determined to be 127 mg/kg of dry matter intake. Increasing Ca:non-phytate P ratios reduced the true Ca digestibility of limestone. The true Ca digestibility coefficients of limestone with Ca:non-phytate P ratios of 1.5, 2.0 and 2.5 were 0.65, 0.57 and 0.49, respectively. Particle size of limestone had a marked effect on the Ca digestibility, with the digestibility being higher in coarse particles (0.71 vs. 0.43).


The non-conserved region of MRP is involved in the virulence of Streptococcus suis serotype 2.
Muramidase-released protein (MRP) of Streptococcus suis serotype 2 (SS2) is an important epidemic virulence marker with an unclear role in bacterial infection. To investigate the biologic functions of MRP, 3 mutants named Δmrp, Δmrp domain 1 (Δmrp-d1), and Δmrp domain 2 (Δmrp-d2) were constructed to assess the phenotypic changes between the parental strain and the mutant strains. The results indicated that MRP domain 1 (MRP-D1, the non-conserved region of MRP from a virulent strain, a.a. 242-596) played a critical role in adherence of SS2 to host cells, compared with MRP domain 1* (MRP-D1*, the non-conserved region of MRP from a low virulent strain, a.a. 239-598) or MRP domain 2 (MRP-D2, the conserved region of MRP, a.a. 848-1222). We found that MRP-D1 but not MRP-D2, could bind specifically to fibronectin (FN), factor H (FH), fibrinogen (FG), and immunoglobulin G (IgG). Additionally, we confirmed that mrp-d1 mutation significantly inhibited bacteremia and brain invasion in a mouse infection model. The mrp-d1 mutation also attenuated the intracellular survival of SS2 in RAW246.7 macrophages, shortened the growth ability in pig blood and decreased the virulence of SS2 in BALB/c mice. Furthermore, antiserum against MRP-D1 was found to dramatically impede SS2 survival in pig blood. Finally, immunization with recombinant MRP-D1 efficiently enhanced murine viability after SS2 challenge, indicating its potential use in vaccination strategies. Collectively, these results indicated that MRP-D1 is involved in SS2 virulence and eloquently demonstrate the function of MRP in pathogenesis of infection.


Small airway disease is associated with elastic recoil changes in excised human lungs.
We studied 54 excised human lungs, 15 with no emphysema and 39 with varying degrees of emphysema, to examine the relationship of small airway disease and elastic recoil. We found a negative correlation between the total small airway pathology score and the mean internal bronchiolar diameter (r = -0.309, p = less than 0.03), as well as with other measurements of small airway size. The internal bronchiolar diameter correlated well with both the elastic recoil expressed as a percentage of predicted values at 70% of total lung capacity (r = 0.533, p less than 0.001) and elastic recoil expressed as an exponential constant k (r = -0.370, p less than 0.01). Fibrosis of the small airways was associated with a reduced internal bronchiolar diameter (r = 0.460, p less than 0.001), as well as the percentage of predicted elastic recoil at 70% of total lung capacity (r = -0.382, p less than 0.01) and elastic recoil expressed as an exponential constant k (r = 0.348, p less than 0.02). We have concluded that changes in elastic recoil seen in these lungs and fibrosis of small airways may be related by a common inflammatory process.


Molecular basis of the inhibition of beta s-chain-dependent polymerization by mouse alpha-chain. Semisynthesis of chimeras of human and mouse alpha-chains.
The transgenic mouse models expressing beta s-globin genes do not fully exhibit the sickling phenotype, primarily as a result of the inhibition of beta s-chain-dependent polymerization by the mouse alpha-chains. The mouse alpha-chain differs from the human alpha-chain at 19 sequence locations. Of these, only alpha 78 and alpha 116 are the known hemoglobin (Hb) S polymer contact sites. To define whether the inhibition of polymerization by the mouse alpha-chain is solely a consequence of the differences at these two sites or additional sites of sequence differences are also involved, we have constructed chimeric alpha-chains by employing the alpha-globin semisynthetic reaction (Sahni, G., Cho, Y. J., Iyer, K. S., Khan, S. A., Seetharam, R., and Acharya, A. S. (1989) Biochemistry 28, 5456-5461). Mouse alpha 1-30 was spliced with human alpha 31-141 using endoproteinase Glu-C to generate a chimeric alpha-globin (alpha MH) containing eight of the 19 sequence differences of mouse alpha-globin. Similarly, human alpha 1-30 was spliced with mouse alpha 31-141 to generate another chimeric alpha-globin (alpha HM) containing 11 sequence differences. The respective chimeric globins were purified, reconstituted with heme and beta s-chain into tetrameric hemoglobin, and the tetramers were purified by ion-exchange chromatography. The inhibitory potential of the chimeric alpha MH-chain on the polymerization is 10-fold lower than that of the mouse alpha-chain. The absence of the alpha 31-141 region of the mouse alpha-chain relieves only a portion of the inhibition. The inhibitory potential of alpha MH contributed by the mouse alpha 1-30 segment is significant although none of the sequence differences in this segment are located at any of the implicated polymer contact sites. The chimeric alpha HM-chain also inhibits the polymerization, but the extent of inhibition is again lower (4-fold) than that of the full-length mouse alpha-chain. The results demonstrate that the inhibitory potential of mouse alpha-chains involves the sequence differences from both the alpha 1-30 and alpha 31-141 regions. Besides, since the sum of the inhibitory potential of either of these chimeric alpha-chains is lower than that of the intact mouse alpha-chains, we speculate that conformational changes that require the copresence of sequence differences in both portions of the mouse alpha-chain also contribute to the inhibitory propensity of the mouse alpha-chain.


Applying artificial intelligence using routine clinical data for preoperative diagnosis and prognosis evaluation of gastric cancer.
The present study employed artificial intelligence (AI) machine learning technology to evaluate the prognosis of gastric cancer using blood collection data, commonly used in clinical practice and subsequently performed a stratification distinct from conventional tumor-node-metastasis (TNM) classification. Experiments were conducted using four machine learning methods, namely, logistic regression (LR), random forest (RF), gradient boosting (GB) and deep neural network (DNN), to classify good or poor post-5-year prognosis based on clinicopathological data and post-5-year relapse occurrence. For each machine learning method, the importance was sorted in descending order (from the most to the least); the top features were used for clustering using the k-medoids method. The prediction accuracy and area under the curve (AUC) for 5-year survival were as follows: LR, 76.8% and 0.702; RF, 72.5% and 0.721; GB, 75.3% and 0.73; DNN, 76.9% and 0.682, respectively. The prediction accuracy and AUC for 5-year recurrence-free survival were as follows: LR, 85.5% and 0.692; RF, 79.0% and 0.721; GB, 80.5% and 0.718; DNN, 83.2% and 0.670. Clustering patients into three groups resulted in a stratification distinct from the TNM classification. In conclusion, AI machine learning using routine clinical data can help evaluate the prognosis of gastric cancer, with prognosis differing according to AI-identified clusters.


Determinants of vascular structure and function in at-risk children born to mothers managed for pre-eclampsia (FINNCARE study).
Pre-eclampsia (PE) is related to elevated blood pressure (BP) in children. The study aims to investigate if elevated BP is reflected in child arterial health and how anthropometrics, body composition, and gestational and perinatal factors influenced this. In this prospective cohort study, we assessed the arteries of 182 children exposed (46 had an early onset, with a diagnosis before 34 gestational weeks, and 136 had a late onset) and 85 children unexposed (non-PE) to PE at 8-12 years from delivery using ultra-high-frequency ultrasound in addition to ambulatory and central BPs, body composition and anthropometrics, and tonometry-derived pulse wave velocity (PWV). No differences were found in intima-media thickness (IMT), adventitia thickness (AT), lumen diameter (LD), local carotid artery stiffness, distensibility, or wall stress between PE-exposed and non-PE-exposed children. All children's brachial, radial, and femoral artery IMTs were associated with 24-h systolic BP (SBP) and pulse pressure, carotid-femoral PWV, and anthropometric measures. The 24-h SBP and anthropometrics, notably lean body mass, were independent predictors of peripheral artery IMTs (brachial R2 = 0.217, radial R2 = 0.208, femoral R2 = 0.214; p < 0.001). Head circumference predicted carotid artery IMT and LD (β = 0.163, p = 0.009; β = 0.417, p < 0.001, respectively), but carotid artery IMT was not associated with BP. No independent associations were found for peripheral artery ATs. Local carotid artery stiffness, distensibility, and wall stress were independently associated with adiposity. No significant associations were found between gestational or perinatal factors and child vascular health parameters. The peripheral artery IMT of PE-exposed children is identical to that of non-PE-exposed children, but associated with BP. Adiposity is related to local carotid artery stiffness. These adverse associations in arterial health may reflect the early progression of cardiovascular disease in PE-exposed children.


Birth Order and First Sexual Experience: Do Siblings Influence Sexual Debut in Adolescents?
Birth order may foster specific roles for individuals within the family and set in train a dynamic that influences the development of specific behaviors. In this paper, we explored the relationship between birth order, sex, timing of sexual initiation, and its consequences for risky sexual behavior and sexual health. We conducted a path analysis to simultaneously estimate direct and indirect effects using data from the National Survey of Sexual Attitudes and Lifestyles (NATSAL-3). Whereas women born as only-children were more likely to sexually debut at later ages, middle-child boys were significantly more prone to initiate sexual intercourse earlier compared with first-borns. As expected, early sexual initiation was associated with riskier behaviors and sexual health outcomes. These associations were partially moderated by siblings role as confidants about sexuality. Our findings have implications for preventive programs aimed at promoting healthy sexual debuts and behaviors over the life span.


Paramagnetic 19F chemical shift probes that respond selectively to calcium or citrate levels and signal ester hydrolysis.
Paramagnetic magnetic resonance chemical shift probes containing a proximal CF(3) group have been characterised. Different systems have been created that report reversible changes in calcium ion concentrations in the millimolar regime, signal the presence of citrate selectively in competitive aqueous media and allow the monitoring of remote ester/amide hydrolysis in relayed, irreversible transformations. Chemical shift non-equivalence is amplified by the presence of the proximate lanthanide ion, with a mean separation between the CF(3) group and the metal ion of 6.4 Å found for a thulium complex, in an X-ray structure of the metal complex aqua adduct. The enhanced rate of longitudinal relaxation of the (19)F nucleus allows faster data acquisition.


[Reconstruction of a cervical esophagus segment with an artificial prosthesis by use of a polyurethane stent covered with collagen-chitosan sponge in dogs].
To repair esophageal defects with an artificial prosthesis composed of biodegradable materials and nonbiodegradable materials, which is gradually replaced by host tissue. The artificial esophagus was a two-layer tube consisting of a chitosan-collagen sponge and an inner polyurethane stent with a diameter of 20 mm and a length of 50 mm. We used the artificial esophagus to replace 5 cm esophageal defects in group I (five dogs) and in group II (ten dogs), and nutritional support was given after operation. The inner polyurethane stent was removed after 2 weeks in group I and after 4 weeks in group II endoscopically and epithelization of the regenerated esophagus was observed by histologic examination and transmission electron microscope. In group I, the polyurethane stent was removed after 2 weeks, and partial regeneration of esophageal epithelial was observed; and constriction of the regenerated esophagus progressed and the dogs became unable to swallow after 4 weeks. In group II, the polyurethane stent was removed after 4 weeks, highly regenerated esophageal tissue successfully replaced the defect and complete epithelization of the regenerated esophagus was observed. After 12 weeks, complete regeneration of esophageal mucosa structures, including mucosal smooth muscle and mucosal glands and partial regeneration of esophageal muscle tissue were observed. Esophageal high-order structures can be regenerated and provided a temporary stent and support by polyurethane stent and an adequate three-dimensional structure for 4 weeks by collagen-chitosan sponge.


[Transabdominal and transrectal ultrasound assessment of intravesical prostatic protrusion].
Benign prostatic hyperplasia (BPH) is one of the most common urological diseases among men. Despite the noticeable positive effects of pharmacotherapy on the quality of urination in BPH, the presence of an intravesical obstruction (IVO) leads to discontinuation of conservative treatment in favor of surgical interventions. One of the features of prostate enlargement is the degree of its intravesical growth (intravascular prostatic protrusion, IPP). According to some studies, IPP value of 10 mm or more is indicative of IVO in virtually all men. To compare transabdominal and transrectal ultrasound measurement of IPP in men with BPH. The study comprised 108 men aged 69+/-10 years (43 to 93 years) with lower urinary tract symptoms and BPH. Patients underwent a standard urological examination. The shape of the prostate, prostate volume and the measurements of the IPP were assessed using transabdominal and transrectal ultrasound. The IPP measurements obtained using transabdominal and transrectal ultrasound were 9.8+/-5.7 mm (1.1 to 28 mm) and 9.3+/-5.3 mm (0.5 to 26 mm), respectively. The IPP measurements evaluated by transabdominal and transrectal ultrasound were found comparable regardless of the prostate volume. Similar results in assessing PPI by both ultrasound modalities allow them to be used equally effectively.


Association of clinical manifestations of secondary lymphedema and lymph node dissection sites in the lower extremities of patients with melanoma.
Lymphedema is a chronic, debilitating disease that often requires life-long management. Predicting clinical manifestations and prognosis is crucial in clinical practice because the treatment of lymphedema should be individualized for best clinical outcome. The aim of this study is to explore the location and severity of lymphedema secondary to inguinal and/or iliac lymph node dissection (LND) in patients with melanoma. Patients with melanoma who received LND at a single tertiary medical center between 1 January 2010 and 31 September 2022 were retrospectively reviewed. Patient who received inguinal LND only were designate as the inguinal group while those who received both ilioinguinal LND were included in the ilioinguinal group. Volumetric measurement was used to objectify the severity and location of lymphedema. Clinical data was acquired for 12-15 months of follow-up. Among 81 patients, 43 (53%) had developed lymphedema in the lower extremities at an average of 33 days after the surgery. Initially, patients manifested with medial thigh lymphedema in the inguinal group while patients were presented with whole leg lymphedema in the ilioinguinal group. Lower leg volume of the ilioinguinal group was significantly higher than the inguinal group. After more than 12 months of lymphedema treatment, upper leg volume was higher in the ilioinguinal group than the inguinal group (12.7% vs 5.4%, p < 0.05). Lymphedema developed in early post-op period. The ilioinguinal group presented with a larger volume of lymphedema in the distal area of the legs. Even after sufficient treatment, predominant lymphedema remained in the proximal leg for the ilioinguinal group. Patients with both inguinal and iliac LND were associated with more severe lymphedema. Based on the dissection sites, the clinical manifestations and prognosis of leg lymphedema can vary widely. Thus, clinicians should consider the dissection site when approaching melanoma patients with lymphedema.


Spread of vector-borne diseases and neglect of Leishmaniasis, Europe.
The risk for reintroduction of some exotic vector-borne diseases in Europe has become a hot topic, while the reality of others is neglected at the public health policy level. Leishmaniasis is endemic in all southern countries of Europe, with approximately 700 autochthonous human cases reported each year (3,950 if Turkey is included). Asymptomatic cases have been estimated at 30-100/1 symptomatic case, and leishmaniasis has up to 25% seroprevalence in domestic dogs. Even though leishmaniasis is essentially associated with Leishmania infantum and visceral leishmaniasis, new species, such as L. donovani and L. tropica, might colonize European sand fly vectors. Drug-resistant L. infantum strains might be exported outside Europe through dogs. Despite this possibility, no coordinated surveillance of the disease exists at the European level. In this review of leishmaniasis importance in Europe, we would like to bridge the gap between research and surveillance and control.


Role of alpha-lipoic acid in ameliorating Cyclosporine A-induced pancreatic injury in albino rats: A structural, ultrastructural, and morphometric study.
The aim of this study was to investigate the effectiveness of alpha-lipoic acid (α-LA) against cyclosporine A (CsA)-induced pancreatic toxicity in rats. Thirty-two male albino rats were divided into four equal groups. Group I treated orally (per os, p.o.) with vehicles and served as control; Group II received α-LA (100 mg/kg b.w. /day, p.o.) for 21 days; Group III received CsA (25 mg/kg b.w./day, p.o.) for 21 days; and Group IV received α-LA 1 hr before oral treatment by CsA for 21 days. Histological examination of the pancreas of CsA-treated rats showed marked changes represented by wide interlobular septae that contained congested blood vessels, cytoplasmic vacuolation of some acinar cells, and distortion of the other cells. Most of the islets of Langerhans showed vacuolation, degenerative changes, and loss of uniform cellular distribution. Some of the islets appeared shrunken with few cells. In the CsA group, the immunohistochemical and morphometric study demonstrated a decrease in the number of insulin-secreting β-cells and also a reduction in islet diameters, with statistically significant difference (p < 0.001 and p = 0.004), respectively, compared with the control group. Ultrastructure of the exocrine and endocrine pancreatic cells of the CsA-treated group confirmed the light microscopic observation and showed dilated rough endoplasmic reticulum, decreased zymogen and secretory granules, damaged mitochondria, and abnormal nuclei. However, α-LA administration simultaneously with CsA resulted in some sort of regression of the previously mentioned effects. α-LA attenuated CsA-induced structural and ultrastructural changes in pancreatic cells, which were nearly reverted to their normal structure.


The value of surgical admissions for malignant uterine cancer. A comparative analysis of robotic, laparoscopic, and laparotomy surgery in a university hospital.
Robotic surgery for malignant uterine cancer raises issue of economic sustainability for providers. The objective of this study was to assess the value of surgical admissions for malignant uterine cancer in a University Hospital through an analysis of their costs and outcomes by comparing three different surgical approaches (laparotomy, laparoscopic, and robotic surgery). Hospitalizations between 1 January 2019 and 31 October 2021 for malignant uterine cancer surgery were selected and stratified. For each surgical approach, mean values (with 95% confidence intervals, CI) were calculated for cost items. Moreover, 30-day readmission frequency was calculated for the three approaches compared to each other. ANOVA and Student's t-test and relative risk (RR) were used for statistical analysis. A break-even analysis was carried out by evaluating the volume of robotic and non-robotic surgical admissions. A total of 1,336 hospitalizations were included in the study, 366 with robotic, 591 with laparoscopic, and 379 with laparotomy surgery. Robotic surgery, compared to laparoscopic and laparotomy ones, showed a statistically significant difference (p < 0.001) in the economic margin, which was largely negative (-1069.18 €; 95%CI:-1240.44--897.92 €) mainly due to devices cost, and a lower percentage of 30-day readmissions (1.4%; 95%CI: 0.2-2.6%), with a statistically significant difference only vs. laparotomy (p = 0.029). Laparoscopic compared to laparotomy surgery showed a significantly (p < 0,001) more profitable economic margin (1692.21 €; 95%CI: 1531.75 €-1852.66 €) without a significant difference for 30-day readmissions. Break-even analysis showed that, on average, for each malignant uterine cancer elective surgery performed laparoscopically, 1.58 elective robotic surgeries are sustainable for the hospital (95% CI: 1.23-2.06). Break-even analysis could be a useful tool to support hospital management in planning and governance of malignant uterine cancer surgery. Systematic application of this tool will allow defining over time right distribution of robotic, laparoscopic, and laparotomy surgeries' volumes to perform to ensure both quality and economic-financial balance and therefore value of uterine oncological surgery. Concerning research, this study paves the way for a multicentric study, the extension of outcomes of malignant uterine surgery to be considered and assessed, and the future inclusion of other therapeutic interventions in the analysis.


The use of cholecalciferol in patients with hip fracture.
Major osteoporotic fractures are steadily increasing due to population aging. Programs of secondary prevention against refracture are essential to decrease morbidity and mortality and the cost for individuals and the society. Vitamin D supplementation and optimization of calcium intake are of a pivotal importance to start specific osteoporosis treatment and for its safety and efficacy. Cholecalciferol is the most widely employed drug for vitamin D supplementation. Aim of this study was to assess the trends in the use of vitamin D supplements containing cholecalciferol in the population of hip fracture patients older than 65 years, resident in the region of Tuscany (Italy) in the years 2011-2015 and to describe vitamin D status in a subgroup of this individuals directly referred to a bone clinic for further evaluation after hip osteoporotic fracture. Data were retrieved from the electronic anonymous regional administrative database administered by the Region of Tuscany (Italy) in the years 2011-2015 within the T.A.R.Ge.T. project (Trattamento Appropriato delle Rifratture Geriatriche in Toscana, i.e., "Appropriate treatment of geriatric refractures in Tuscany"), a program endorsed by the region itself. Data pertaining to cholecalciferol prescriptions and hospital discharge codes were retrieved and appropriately crossed to get data on the use of cholecalciferol supplements in patients before and after a hip fracture. A retrospective analysis was carried out in a subgroup of subjects (n 254) appropriately referred to the local fracture liaison service after the major osteoporotic fracture and vitamin D status in terms of serum 25(OH) vitamin D levels was assessed. The majority of subjects experiencing a hip fracture (98.2% and 88.3% in 2011 and 2015, respectively) did not receive vitamin D supplements at the time of the fracture event. Although a trend in increase in prescriptions for cholecalciferol supplements could be observed in the years of the study, the percentage of treated individuals remained low even after the fracture, since only 30-35% of subjects receives cholecalciferol supplements at one year after the fracture. Cholecalciferol remained the most prescribed drug in this population, while a substantial decrease of cholecalciferol in association with calcium salts was observed. The use of high doses of cholecalciferol has decreased in this population, while diminished the use of the drops has been accompanied by an increase in prescriptions of single monthly dose supplements. The correction of vitamin D inadequacy is preliminary to any treatment for osteoporosis and together with calcium may reduce fracture risk by itself. The prescription of vitamin D supplements is low in patients before and after a hip fracture in a Mediterranean region and despite the overall increase in vitamin use and abuse in the general population. Proper educational programs and active fracture liaison services are needed in order to bridge this gap.


Changes in the DNA content of adrenal medulla nuclei of rats intermittently exposed to cold.
In the adrenal medulla of rats exposed intermittently to cold (+4 degrees C) for 100 and 300 hours, a considerable decrease (24 to 40 per cent) of the DNA content per nucleus was observed, followed by restoration to normal or above normal values within 10 days after the withdrawal of the stimulus. The findings were obtained with a scanning integrating histophotometer, and confirmed by microinterferometric investigations (on the basis of the measurement of total dry mass of nuclei isolated in aqueous medium before and after treatment with DNase) and by microchemical determinations, combined with the count of the nuclei in the homogenates. The observed decrease of DNA content cannot be attributed to errors of the methods used, nor to consequences of cellular degeneration. The available evidence seems to indicate a real decrease rather than a change in the state of a part of DNA in the nucleus in vivo whereby it becomes extractable by aqueous solutions. The restoration cannot be due to mitotic processes, which were actually never detected even with the use of colchicine, since the adrenal medulla cells in the adult rat are known to be irreversible, postmitotic cells. A correlation between the functional activity of the adrenal medulla cells and the content or state of DNA in their nuclei is demonstrated.


Control of influenza in the hospital.
Nosocomial transmission of influenza has been reported infrequently; however, patients in general hospitals are often among the most susceptible to the complications of influenza infection. Hospital-acquired influenza may occur more often than is reported, but it may be recognized because of lack of diagnostic facilities or the time required for virus isolation and identification. Based on the mode of transmission in the hospital, the established reservoirs of influenza virus, and duration of virus shedding, isolating patients with influenza may occasionally be useful but restricting visitors is probably not required. Vaccinating hospital personnel with influenza vaccine and, if influenza A is prevalent, giving amantadine hydrochloride to high-risk patients or personnel should both be considered.


Physical fitness in children with hemophilia.
Eleven boys, 8.3 to 15.5 (mean 11.6) years old, with hemophilia, were studied by bicycle ergometry to determine their physical fitness. Parameters analyzed and compared to data for normal children included total work, mean power minutes of exercise, heart rate (HR), and blood pressure (BP), as well as catecholamine levels. The hemophilic child performs significantly less total work (67%), mean power (49%), minutes of exercise, (30%), and HR (8%). There were no differences in BP. Norepinephrine rose from a resting level of 204.5 to 652pg /ml after exercise, and epinephrine rose from 20.5 to 76.6pg/ml, levels comparable to those achieved by normal children during exercise. Children with hemophilia demonstrate poor exercise performance, which we believe is due to a lack of physical conditioning. Recommendations are made for individual exercise prescriptions to improve the fitness of these children.


Should all living donors be treated equally?
Recently, Matas et al. described a protocol to accept as potential donors altruistic strangers who offer to donate a kidney to any patient on the waiting list. The selection of donors would be the same as the process they use for living, emotionally related donors, except that the full work-up would have to be done at their institution and would include a detailed psychosocial evaluation. In this article, we present a case that raised the question of whether the medical standards for nonemotionally related donors should be the same as the standards for emotionally related donors. We argue that we must distinguish between the altruistic donation by a stranger and the voluntary donation by an emotionally related individual. We argue that voluntary donations have a degree of moral obligation based on intimacy and that intimacy allows, but does not require, that these donors take on slightly additional risk.