Declining trends of premature mortality from ischemic heart disease and regional differences in Italy from 2011 to 2017.
Data regarding the premature mortality (<65 years of age) due to ischemic heart disease (IHD) in Italy are scant. We sought to analyze the incidence of premature death due to IHD in Italy and its time trend between years 2011 and 2017. We used the free publicly available EUROSTAT death certificate database to examine premature age-adjusted IHD mortality rates (per 100.000) and relative average annual percentage change (AAPC) in Italy from 2011 to 2017 using ICD-codes I20-I25. Over the study period, the proportional IHD-related mortality rates decline from 8.09% to 7.1% in the entire population (p for trend 0.012), showing a significant reduction in women (from 4.06% to 3.40%, p for trend: 0.02) but not in men (from 10.3% to 9.3%, p for trend 0.062). The age-adjusted IHD mortality rate decreased with an AAPC of -4.1 per year [(95% CI, -5.1 to -3.0), p < 0.001], resulting more pronounced in women [AAPC: -4.4 per year (95% CI: -6.4 to -2.3,), p = 0.001)] than in men [AAPC: -3.7 per year (95% CI: -5.4 to -2.0, p = 0.003)]. Age-adjusted IHD premature death rates above the 90th percentile were distributed in Italian southern regions and islands of Italy while premature death rates below the 10th percentile were clustered in the western and northeastern regions of the country. In Italy, premature IHD-related mortality remains an important contributor to overall mortality. Age-adjusted mortality declined in the last decade, especially in the northern regions and among women. Moreover, a marked region-level variations were observed.


The evolution of human influenza A viruses from 1999 to 2006: a complete genome study.
Knowledge about the complete genome constellation of seasonal influenza A viruses from different countries is valuable for monitoring and understanding of the evolution and migration of strains. Few complete genome sequences of influenza A viruses from Europe are publicly available at the present time and there have been few longitudinal genome studies of human influenza A viruses. We have studied the evolution of circulating human H3N2, H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human influenza A viruses and characterised 24 complete genomes. H3N2 was the prevalent strain in Denmark during the study period, but H1N1 dominated the 2000-2001 season. H1N2 viruses were first observed in Denmark in 2002-2003. After years of little genetic change in the H1N1 viruses the 2005-2006 season presented H1N1 of greater variability than before. This indicates that H1N1 viruses are evolving and that H1N1 soon is likely to be the prevalent strain again. Generally, the influenza A haemagglutinin (HA) of H3N2 viruses formed seasonal phylogenetic clusters. Different lineages co-circulating within the same season were also observed. The evolution has been stochastic, influenced by small "jumps" in genetic distance rather than constant drift, especially with the introduction of the Fujian-like viruses in 2002-2003. Also evolutionary stasis-periods were observed which might indicate well fit viruses. The evolution of H3N2 viruses have also been influenced by gene reassortments between lineages from different seasons. None of the influenza genes were influenced by strong positive selection pressure. The antigenic site B in H3N2 HA was the preferred site for genetic change during the study period probably because the site A has been masked by glycosylations. Substitutions at CTL-epitopes in the genes coding for the neuraminidase (NA), polymerase acidic protein (PA), matrix protein 1 (M1), non-structural protein 1 (NS1) and especially the nucleoprotein (NP) were observed. The N-linked glycosylation pattern varied during the study period and the H3N2 isolates from 2004 to 2006 were highly glycosylated with ten predicted sequons in HA, the highest amount of glycosylations observed in this study period. The present study is the first to our knowledge to characterise the evolution of complete genomes of influenza A H3N2, H1N1 and H1N2 isolates from Europe over a time period of seven years from 1999 to 2006. More precise knowledge about the circulating strains may have implications for predicting the following season strains and thereby better matching the vaccine composition.


Small RNA-mediated regulation of the tet(M) resistance gene expression in Enterococcus faecium.
We investigated the role of a novel small RNA expressed in Enterococcus faecium (named Ern0030). We revealed that ern0030 was encoded within the 5'untranslated region of tet(M), a gene conferring tetracycline resistance through ribosomal protection. By RACE mapping, we accurately determined the boundaries of ern0030, which corresponded to Ptet. This upstream sequence of tet(M), Ptet, was previously described within transcriptional attenuation mechanism. Here, Northern blot analyses revealed three transcripts of different lengths (ca. 230, 150 and 100 nucleotides) expressed from Ptet. Phenotypically, the total deletion of ern0030 conferred a decrease in tetracycline MICs that was consistent with gene expression data showing no significant tet(M) induction under tetracycline SIC in ern0030-deleted mutant as opposed to a 10-fold increase of tet(M) expression in the wild-type strain. We investigated the transcriptional attenuation mechanism by toeprint assay. Whereas the expected tet(M) ribosome-binding site (RBS) was detected, the RBS of the putative leader peptide was not highlighted by toeprint assay, suggesting the transcriptional attenuation was unlikely. Here, we demonstrate that Ern0030 has a role in regulation of tet(M) expression and propose a novel model of tet(M) regulation alternative or complementary to transcriptional attenuation.


Sustainable dialdehyde polysaccharides as versatile building blocks for fabricating functional materials: An overview.
Dialdehyde polysaccharide (DAP), containing multiple aldehyde groups, can react with materials having amino groups via Schiff base crosslinking. Besides, it can also react with materials having carbonyl/hydroxyl groups via aldol reactions. Based on these intriguing properties, DAPs can be employed as versatile building blocks to fabricate functional materials used in biomedical field, wastewater treatment, leather manufacture, and electrochemistry field. This review aims to provide an overview of the recent advances in fabricating biomaterials, adsorbents, leather tanning agents, and electrochemical materials based on DAPs. The basic fabricating strategy and principle of these materials and their performances are overall summarized, along with a discussion of associated scalability challenges, technological strategies to overcome them, and the prospect for commercial translations of this versatile material. Blending the versatility of DAP with material science and technological advances can provide a powerful tool to develop more DAP-based functional materials in a scalable way.


Can a glucagon stimulation test characterized by lower GH cut-off value be used for the diagnosis of growth hormone deficiency in adults?
The aim of this study was to assess diagnostic values of insulin tolerance test (ITT), glucagon stimulation test (GST), and insulin like growth factor-I (IGF-I) level, to find optimal GH cut-off values for GST, and to evaluate efficiencies of patient age, gender, body-mass index (BMI), and additional pituitary hormone deficiencies (PHDs) in the diagnosis of growth hormone deficiency (GHD). This retrospective study involved 216 patients with a pituitary disease and 26 healthy controls. Age, gender, BMI, medical histories, and hormonal data including baseline and stimulated hormone values were evaluated. Three cut-off values for peak GH responses to stimulation tests were evaluated: (a) 3.00 µg/L on ITT, (b) 3.00 µg/L on GST, and (c) 1.07 µg/L on GST. According to the ITT, GST with 3.00 µg/L cut-off, and GST with 1.07 µg/L cut-off, GHD was present in 86.1, 74.5, and 54.2 % patients, respectively. Patient age, BMI, and number of PHDs, but not gender, were found to be correlated with IGF-I and peak GH concentrations. All patients with an IGF-I concentration ≤95 ng/ml or ≥3 PHD had GHD. None of the patients with adequate GH response to the GST with 1.07 µg/L cut-off, but blunted responses to ITT and GST with 3.00 µg/L cut-off, had ≥3 PHDs. 12 out of 26 (46.2 %) healthy subjects failed the GST with 3.00 µg/L cut-off, but not with 1.07 µg/L cut-off. Patient age, IGF-I, BMI, and number of PHDs are efficient factors associated with the diagnosis of GHD. A 4 h GST with a diagnostic GH threshold of 1.07 µg/L seems to be a good diagnostic method for GHD.


Brainstorming: weighted voting prediction of inhibitors for protein targets.
The "Brainstorming" approach presented in this paper is a weighted voting method that can improve the quality of predictions generated by several machine learning (ML) methods. First, an ensemble of heterogeneous ML algorithms is trained on available experimental data, then all solutions are gathered and a consensus is built between them. The final prediction is performed using a voting procedure, whereby the vote of each method is weighted according to a quality coefficient calculated using multivariable linear regression (MLR). The MLR optimization procedure is very fast, therefore no additional computational cost is introduced by using this jury approach. Here, brainstorming is applied to selecting actives from large collections of compounds relating to five diverse biological targets of medicinal interest, namely HIV-reverse transcriptase, cyclooxygenase-2, dihydrofolate reductase, estrogen receptor, and thrombin. The MDL Drug Data Report (MDDR) database was used for selecting known inhibitors for these protein targets, and experimental data was then used to train a set of machine learning methods. The benchmark dataset (available at http://bio.icm.edu.pl/∼darman/chemoinfo/benchmark.tar.gz ) can be used for further testing of various clustering and machine learning methods when predicting the biological activity of compounds. Depending on the protein target, the overall recall value is raised by at least 20% in comparison to any single machine learning method (including ensemble methods like random forest) and unweighted simple majority voting procedures.


Oblique lateral interbody fusion combined percutaneous pedicle screw fixation in the surgical treatment of single-segment lumbar tuberculosis: A single-center retrospective comparative study.
To evaluate the clinical efficacy of oblique lateral interbody fusion combined posterior percutaneous pedicle screw fixation in the treatment of single segment lumbar tuberculosis. Patients who underwent surgical treatment for single segment lumbar tuberculosis from 2015 to 2018 in our department were retrospectively included in this study. The included patients were divided into two groups, namely oblique lateral interbody fusion combined percutaneous pedicle screw fixation (OLIF) group and traditional posterior transforaminal or transpedicular approach debridement and pedicle screws fixation (PTA) group, according to the surgical methods. Outcomes including operative time, operative blood loss, hospital stay, visual analogue scale (VAS) score, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), Cobb angle correction and loss, bone fusion time, ASIA grade and complications were all recorded and compared. A total of 60 patients were included in this study, involving 23 patients in the OLIF group and 37 patients in the PTA group. The OLIF group had less operative time, blood loss and shorter hospital stay compared with the PTA group (P < 0.05). Both the two groups achieved significant improvements in ESR, CRP and ASIA grade at the last follow-up (P < 0.05), but no significant differences were found between them (P>0.05). There were no significant differences in Cobb angle correction and loss between the two groups (P > 0.05), but the bone graft fusion time of the OLIF group was significantly shorter than the PTA group (P < 0.05). The two groups achieved similar improvement in VAS score and ODI at 12 months postoperative and the last follow-up, however, OLIF group had a lower VAS score and ODI at 1 month, 3 months and 6 months postoperative (P < 0.05). No significant difference was found in complications between the two groups (P > 0.05) and all patients were cured after active treatment. Both OLIF and PTA can achieve satisfactory clinical efficacy in the surgical treatment of single segment lumbar TB, but OLIF has the advantages of less surgical trauma, faster postoperative recovery and shorter bone fusion time.


Response surface of daily thyroid hormone rhythms in young chickens exposed to constant ambient temperature.
Response surface models were developed by multiple regression techniques to describe daily rhythms of plasma thyroid hormones in young chickens during acclimation to a wide range of ambient temperatures (Ta). Seventy-two Leghorn cockerels were raised in six environmental chambers under a 12L:12D light/dark cycle. Beginning at 21 days of age, two replicate chambers provided Ta treatments of 10, 24, or 38 degrees. During Day 6 of acclimation, blood samples were obtained at 0800, 1200, 1600, 2000, 2400, and 0400 hr for thyroid hormone analyses. Plasma triiodothyronine (T3) levels showed a convex response to the experimental region (10 to 38 degrees, and 0800 to 0400 hr under a 12L:12D light/dark cycle), whereas the plasma thyroxine (T4) response surface was concave. In particular, heat exposure (38 degrees) depressed (P less than .01) plasma T3 levels (2.8 ng/ml) below those of birds held at 24 degrees (4.5 ng/ml), whereas elevated (p less than 0.05) T3 concentrations were found in the 10 degrees treatment (5.0 ng/ml). Plasma T3 levels rose gradually during photophase and slowly declined during scotophase. Plasma T4 concentrations followed an opposite pattern with the daily zenith in scotophase and the nadir during photophase. Plasma T4 levels were sharply elevated in birds maintained at 38 degrees, particularly during scotophase. Although Ta did not change the daily amplitude or circadian frequency of the plasma T3 rhythm, an increased frequency or ultradian rhythm of plasma T4 was observed in cold-acclimated birds. The counter-responses of T3 and T4 to heat exposure and phase of the light/dark cycle were best seen in the molar ratio of plasma T3/T4 levels. The average daily T3/T4 molar ratio for heat-exposed birds was 0.16 while the average T3/T4 ratio was higher (P less than 0.01) for the 10 degrees (0.46) and 24 degrees (0.41) treatments. The opposing responses of plasma T3 and T4 levels to a wide range of Ta and phase of the light/dark cycle support a major role for circulating T3 in metabolic adjustments that chickens make to changes in the photothermal environment.


Prevalence and antibiotic susceptibility of coagulase-negative Staphylococcus species from bovine subclinical mastitis in dairy herds in the central region of Argentina.
Coagulase-negative staphylococci (CNS) are a common cause of bovine subclinical mastitis (SCM). The prevalence of CNS species causing SCM identified by genotyping varies among countries. Overall, the antimicrobial resistance in this group of organisms is increasing worldwide; however, little information exists about a CNS species resistant to antibiotics. The aim of the present study was to genotypically characterize CNS at species level and to determine the prevalence and antibiotic resistance profiles of CNS species isolated from bovine SCM in 51 dairy herds located in the central region of the province of Cordoba, Argentina. In this study, we identified 219 CNS isolates at species level by PCR-restriction fragment length polymorphism of the groEL gene. Staphylococcus chromogenes (46.6%) and Staphylococcus haemolyticus (32%) were the most prevalent species. A minimum of three different CNS species were present in 41.2% of the herds. S. chromogenes was isolated from most of the herds (86.3%), whereas S. haemolyticus was isolated from 66.7% of them. The broth microdilution method was used to test in vitro antimicrobial susceptibility. Resistance to a single compound or two related compounds was expressed in 43.8% of the isolates. S. chromogenes and S. haemolyticus showed a very high proportion of isolates resistant to penicillin. Resistance to two or more non-related antimicrobials was found in 30.6% of all CNS. S. haemolyticus exhibited a higher frequency of resistance to two or more non-related antimicrobials than S. chromogenes.


Aqueous Seeding in Retinoblastoma: Classification and Clinicopathologic Correlation.
To correlate the clinical types of aqueous seeds with histopathologic characteristics in primarily enucleated eyes with retinoblastoma (RB). Retrospective study. Twenty-five patients with RB. Clinicopathologic correlation of aqueous seeds in 25 eyes that underwent primary enucleation and showed evidence of aqueous seeds. Histopathologic characteristics of aqueous seeds. All 25 enucleated eyes were classified as group E RB based on the International Classification of Intraocular Retinoblastoma. Clinically, type 1 aqueous seeds were noted in 9 (36%) eyes, type 2 in 8 (32%), and type 3 in 8 (32%). Based on histopathology, type 1 seeds were defined as individual tumor cells admixed with macrophages and nonviable tumor cells. Type 2 seeds were defined as spheres and classified into 2 subtypes: (1) spheres without central necrosis containing solid clusters of tumor cells and (2) spheres with central necrosis containing a central core of necrotic cells surrounded by viable tumor cells. Type 3 seeds were defined as tumor cells admixed with macrophages and red blood cells sedimented at an angle. Aqueous seeding involved both anterior (n = 25; 100%) and posterior (n = 18; 72%) chambers. Significant infiltration of RB into the intraocular tissue (Schlemm canal, trabecular meshwork, ciliary body, choroid, optic nerve, and sclera) was noted in 23 cases (92%). Compared with eyes with type 1 and 2 seeds, eyes with type 3 seeds were more commonly associated with ciliary body infiltration (41% vs. 88%, respectively; P = 0.04). Over a mean follow-up period of 57 months (median, 49 months; range, <1-175 months), metastasis and death were noted in 3 patients (12%). Similar to vitreous seeds in RB, aqueous seeds have 3 distinct histopathologic types. Posterior chamber seeds were noted in 72% of cases presenting with anterior chamber (AC) seeds, indicating the need for the treatment of both the chambers whenever conservative treatment is attempted in suitable cases. Most (92%) cases with primary aqueous seeding are associated with other high-risk histopathology features, suggesting a cautious approach to conservative management in these cases.


Exposure therapy for emetophobia: a case study with three-year follow-up.
Emetophobia, also referred to as a specific phobia of vomiting, is a largely under-researched and poorly understood disorder with prevalence estimates of ranging between 1.7 and 3.1% for men and 6 and 7% for women (Hunter & Antony, 2009; Philips, 1985). The current case study, therefore, sought to methodically apply exposure-based behavioral treatment to the treatment of a 26 year-old, Hispanic, female suffering from emetophobia. Although not as powerful as a randomized design, this description may still add to the existing emetophobia literature through the illustration of adaptation of published behavioral treatments for other specific phobias. The case presented was successful in terms of outcome, and includes a three-year follow up wherein treatment gains were measurably maintained.


Effects of a foot bath containing green tea polyphenols on interdigital tinea pedis.
It has been shown that green tea polyphenols (GTP) can directly kill Trichophyton in vitro; however, there are no published clinical studies that show anti-fungal activity of GTP. To identify the effects of GTP on interdigital tinea pedis in elderly patients. Ninety-four patients with interdigital tinea pedis were enrolled and were either given a lukewarm water foot bath containing GTP or placebo treatment. Effects of GTP were assessed based on changes in the size of the affected area, the rate of recurrence, microscopy findings, and overall assessment of skin changes. After 12 weeks of treatment with either GTP or placebo, a significant reduction in the size of the affected area was observed (p<0.001). There were no significant differences between the GTP or placebo groups in the size of the affected area (p=0.638), the recurrence rate (p=0.172), or the microscopy findings (p=1.000). However, the overall assessment demonstrated significant improvements (p=0.010) in the GTP group. These results show that GTP was effective in improving the symptoms of tinea pedis in comparison to only lukewarm water. Our results suggest that GTP could have anti-fungal activity.


Robotic versus laparoscopic right hemicolectomy: a retrospective cohort study of the Binational Colorectal Cancer Database.
Robotic right hemicolectomy (RRC) may have technical advantages over the conventional laparoscopic right colectomy (LRC) due to higher degrees of rotation, articulation, and tri-dimensional imaging. There is growing literature describing advantages of RRC compared to LRC; however, there is a lack of evidence about safety, oncologic quality of surgery and cost. This study aimed to analyse complication rates, length of stay and nodal harvest in patients undergoing minimally invasive right hemicolectomy for colon cancer from a prospective Australasian colorectal cancer database. This was a retrospective cohort study using nearest neighbour matching. The Binational Colorectal Cancer Audit (BCCA) provided the data for analysis. The primary outcome was length of stay. Secondary outcomes were harvested lymph node count, anastomotic leak, postoperative haemorrhage, abdominal abscess, postoperative ileus, wound infections and non-surgical complications. 4977 patients who underwent robotic (n = 146) or laparoscopic (n = 4831) right hemicolectomy for right-sided colon cancer were included. For RRC, LOS was shorter (5 vs 6.9 days, p = 0.01) and nodal harvest was higher (22 vs 19, p = 0.04). For RRC, surgical complications (5.9% vs 14.2%, p < 0.004) and non-surgical complications (4.6% vs 11.7%, p = 0.007) were lower though there was no difference in return to theatre or inpatient death. Robotic right hemicolectomy is associated shorter LOS and marginally higher lymph node count, though this may reflect anastomotic technique rather than surgical platform. Longer term studies are required to establish differences in overall survival, incisional hernia rates and cost effectiveness.


Stability of antibodies to Bordetella antigens in German adults.
To estimate the rate of asymptomatic exposure to Bordetella pertussis antigens in the German adult population and to evaluate the stability of antibodies to these antigens, antibody levels against Bordetella antigens and their variability over time were measured in German adult blood donors. One hundred forty-six regular blood donors (41 females, 105 males) were tested repeatedly for antibodies of isotypes IgG and IgA to pertussis toxin, filamentous hemagglutinin (FHA) and pertactin over a period of 2-5 years. Overall, 86% and 56% had IgG or IgA antibodies to pertussis toxin, respectively, 100% and 92% had IgG or IgA antibodies to FHA, respectively, and 83% and 93% had IgG or IgA antibodies to pertactin, respectively. One significant titer increase of both IgG anti-FHA and IgG anti-pertactin, one of IgG anti-FHA, and two of IgA anti-FHA as well as one significant decrease of IgG anti-pertussis toxin were observed during an observation period of 480.5 person-years. Antibody concentrations in men and women were not different. The data show that the level of antibodies to pertussis toxin, FHA, and pertactin remains stable over several years. Furthermore, depending on the definition of serological evidence, the rate of significant increases or decreases suggesting unrecognized exposure to Bordetella antigens was estimated to be between <0.2 and 1.0 per 100 person-years in the population studied.


Hypomanic-like experiences and spontaneous emotional mental imagery.
Bipolar spectrum disorders (BPSD) are associated with frequent and emotional mental imagery, theorized to play a role in mood instability. However, we lack methods for measuring tendency to experience emotional mental imagery in daily life. The current study developed such a measure and evaluated the hypothesis that a high tendency to experience emotional imagery in daily life would be associated with higher levels of hypomanic-like experiences. We conducted two rounds of studies to develop and refine a measure of spontaneous emotional imagery (E-SUIS) using factor analysis. We conducted a third study to test the relationship between E-SUIS score and hypomanic-like experiences. Participants (total N = 554, age 18-25) comprised an unselected community sample. First, factor analysis indicated a unidimensional factor structure and excellent reliability (α=0.87) of our novel measure of spontaneous emotional mental imagery. Second, higher scores on a hypomanic-like experiences scale related to higher use of both spontaneous emotional imagery and spontaneous non-emotional imagery. Spontaneous emotional mental imagery significantly improved the prediction of hypomanic-like experiences over non-emotional mental imagery. Only two mental imagery measures were included. To determine discriminant validity of the E-SUIS requires additional imagery measures or interviews. Levels of hypomanic-like experiences were related to the tendency to use emotional imagery in daily life. Additionally, spontaneous use of emotional imagery appears to be a better predictor of hypomanic-like experiences in the general population compared to spontaneous use of non-emotional imagery.


The nasolabial musculocutaneous flap: clinical and anatomical correlations.
The location of the facial artery beneath the facial mimetic muscles of the nasolabial groove allows surgical development of a true musculocutaneous flap. This report of 20 surgical flaps and six cadaveric dissections highlights the nasolabial musculocutaneous flap with its direct muscle perforating arteries which nourish the overlying skin. The absence of any flap's ischemic failure emphasizes the durability of the flap for various midface and oral reconstructive situations. Inferiorly-based flaps are preferable on the basis of discussed anatomical findings. The musculocutaneous flap is especially suited for circumferential interruption of cutaneous blood supply as in the "V-to-Y" and island pedicle flaps.


Transcatheter aortic valve implantation (TAVI): valve design and evolution.
The efficacy of transcatheter aortic valve implantation (TAVI) in high surgical risk and inoperable patients with severe aortic stenosis (AS) is rapidly gaining credibility with an ever-expanding body of supporting evidence. The potential of TAVI to be a treatment option for a significant cohort of patients with aortic stenosis has fuelled a drive for the optimum device and resulted in exponential advances in the technology with a focus on adverse event minimization and procedural simplification. Consequently, a plethora of new transcatheter valve choices are now available for clinical study or in the pipeline. The evaluation of past, current and emerging devices allows for an appreciation of the design considerations involved in this process and an insight to the future direction of the technology.


AlphaB-crystallin-reactive T cells from knockout mice are not encephalitogenic.
Alpha B-crystallin (alphaB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for alphaB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained alphaB-knockout (alphaB-KO) mice in H-2b background that lack immune tolerance to alphaB protein, and thus are capable of developing alphaB-specific T cells that could be tested for encephalitogenic activity after transfer into alphaB-expressing wild type (WT) mice. We found that T cell lines from spleens of alphaB protein-immunized alphaB-KO mice proliferated strongly to alphaB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such alphaB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, alphaB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of alphaB message in the CNS at the time of transfer. These results suggest that alphaB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of alphaB.


Complex O-acetylation in non-typeable Haemophilus influenzae lipopolysaccharide: evidence for a novel site of O-acetylation.
The structure of the lipopolysaccharide (LPS) of non-typeable Haemophilus influenzae strain 723 has been elucidated using NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) on O-deacylated LPS and core oligosaccharide material (OS), as well as ESI-MSn on permethylated dephosphorylated OS. It was found that the LPS contains the common structural element of H. influenzae, l-alpha-D-Hepp-(1-->2)-[PEtn-->6]-l-alpha-D-Hepp-(1-->3)-[beta-D-Glcp-(1-->4)]-l-alpha-D-Hepp-(1-->5)-[PPEtn-->4]-alpha-Kdo-(2-->6)-Lipid A, in which the beta-D-Glcp residue (GlcI) is substituted by phosphocholine at O-6 and the distal heptose residue (HepIII) by PEtn at O-3, respectively. In a subpopulation of glycoforms O-2 of HepIII was substituted by beta-D-Galp-(1-->4)-beta-D-Glcp-(1--> or beta-D-Glcp-(1-->. Considerable heterogeneity of the LPS was due to the extent of substitution by O-acetyl groups (Ac) and ester-linked glycine of the core oligosaccharide. The location for glycine was found to be at Kdo. Prominent acetylation sites were found to be at GlcI, HepIII, and the proximal heptose (HepI) residue of the triheptosyl moiety. Moreover, GlcI was acetylated at O-3 and/or O-4 and HepI was acetylated at O-2 as evidenced by capillary electrophoresis ESI-MSn in combination with NMR analyses. This is the first study to show that an acetyl group can substitute HepI of the inner-core region of H. influenzae LPS.


Prognostic Signals From Moderate Valve Disease in Big Data: An Artefact of Digital Imaging and Communications in Medicine Structured Reporting?
Recent studies have identified an association between moderate aortic stenosis (AS) and outcome. We assessed whether Digital Imaging and Communications in Medicine (DICOM) structured reporting (SR), which captures and inserts echocardiographic measurements and text data directly into radiological reports, may lead to misclassifying patients with severe AS as moderate. Moderate or severe AS cases were filtered from an echocardiography data set based on aortic valve area (AVA) < 1.5 cm2, indexed AVA (AVAi) ≤ 0.85 cm2/m2, mean pressure gradient ≥ 25 mm Hg, dimensionless severity index (DSI) ≤ 0.5, or peak velocity > 3 m/sec. Data validation was conducted by verification of each parameter. All echocardiographic parameters and definitions of AS were compared pre- and postvalidation by taking differences in measurements. Misclassification rates were assessed by determining the percentage of cases that changed AS severity classification and impact on outcomes. Patients were followed over 4.3 ± 1.5 years. Of 2,595 validated echocardiograms with AS, up to 36% of the echocardiographic parameters for AS criteria had a >10% difference between DICOM-SR and manual validation, the highest with mean pressure gradient (36%) and the lowest with DSI (6.5%). The validation process changed the reported degree of AS in up to 20.6% of echocardiograms with resultant changes in AS severity and its association with mortality or heart failure-related hospitalizations. In contrast to multiple quantitative metrics in DICOM-SR after manual validation, clinicians' evaluation of AS severity was unable to distinguish composite outcomes over 3 years between moderate and severe AS. The risk of composite outcomes was significantly increased when severe AS was evidenced by at least 1 echocardiographic parameter of severe AS (hazard ratio = 1.24; 95% CI, 1.12-1.37; P < .001). The greatest hazard was based on DSI only (hazard ratio = 1.26; 95% CI, 1.10-1.44; P < .001), which was higher after manual validation compared to DICOM-SR. Averaging of repeated echo measures including invalid values contributed the most to erroneous data. Nonpeak data in DICOM-SR led to incorrect categorization of a high proportion of patients based on AS severity definitions. Standardization of data fields and curation to ensure that only peak values are imported from DICOM-SR data are essential.


[Population structure of the Baikalian amphipod Gmelinoides fasciatus (Stebbing)].
Using the data on 71 individual sequences of the gene for the mitochondrial cytochrome-c-oxidase subunit one, molecular and phylogenetic characterization of the Baikalian amphipod, Gmelinoides fasciatus (Crustacea, Amphipoda), was performed. Interspecific polymorphism was demonstrated. Four main amphipod populations, Southeastern, Southwestern, Northern, and Central, were distinguished. A low level of genetic diversity typical of Southwestern population was revealed. For its explanation, the bottleneck hypothesis was proposed.


Study of local atomic order in amorphous materials in a computerized transmission electron microscope.
Experimental results obtained by electron diffraction (ED) and extended electron energy loss fine structure (EXELFS) techniques to study the local atomic order in amorphous materials such as carbon, silicon, and its oxides are described. Potential applications of ED and EXELFS techniques and their limitations are also discussed.


Conservative management of a complication of neonatal teeth: a case report.
A case report of neonatal teeth in a 4 month old male infant with ulceration on ventral surface of the tongue and its conservative management, is presented.


Molluscicidal activity against Oncomelania hupensis of Ginkgo biloba.
In search for molluscicidal active components, petroleum ether, ethyl acetate, ethanol, and water extracts from Ginkgo sarcotesta were evaluated against the snail Oncomelania hupensis. The bioassay-oriented showed that the activity concentrates in the petroleum ether extract (LD(50) 7.81 ppm). Ginkgolic acids, isolated from the petroleum ether extract, exhibited strong molluscicidal activity (LD(50) 1.49 ppm), gingkgolic acid C15:1 having the strongest molluscicidal activity.


Longitudinal Heart Failure Medication Use and Adherence Following Left Ventricular Assist Device Implantation in Privately Insured Patients.
There are few data describing the longitudinal use of and adherence to heart failure medications following left ventricular assist device (LVAD) implantation. Using a large US commercial insurance database, patients who received an LVAD (International Classification of Diseases, 9th Revision, Clinical Modification code 37.66) and survived to hospital discharge without heart transplantation between January 1, 2006, and March 31, 2015, were identified. Heart failure medication use from 3 months before 1-year post-LVAD was examined using linked pharmacy claims. Differences in the proportion of patients taking heart failure medications post LVAD compared with pre LVAD were examined using McNemar test. Predictors of post-LVAD medication use and poor medication adherence (proportion of days covered <0.8) were identified via logistic regression. Among 362 patients (mean age, 57.4 years; 75.1% men), compared with pre LVAD, the proportion of patients taking anticoagulants and antiarrhythmics following LVAD increased; mineralocorticoid receptor antagonists, thiazide diuretics, and digoxin decreased; and β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and loop diuretics did not change. Pre-LVAD medication use was associated with post-LVAD use across all medication classes. The proportion of patients with poor medication adherence was 28.8%, 39.0%, and 36.0% for β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and anticoagulants, respectively. Many patients with poor adherence completely discontinued use of the medication. Neurohormonal antagonist use after LVAD was inconsistent, perhaps reflecting uncertainty of therapeutic benefit in this population. Medication adherence post-LVAD was poor in many patients. Further work is needed to delineate the reasons for nonadherence after LVAD.


Antigenic variation among group A streptococcal M proteins. Nucleotide sequence of the serotype 5 M protein gene and its relationship with genes encoding types 6 and 24 M proteins.
The 1479-base pair (bp) nucleotide sequence of the serotype 5 M protein gene (smp5) from Streptococcus pyogenes contains three distinct types of tandemly repeated sequences, designated A, B, and C. Repeat A (21 bp x 6, in the 5'-half of smp5), shares no homology with the types 6 or 24 M protein genes (Hollingshead, S. K., Fischetti, V. A., and Scott, J. R. (1986) J. Biol. Chem. 261, 1677-1686; Mouw, A. R., Beachey, E. H., and Burdett, V. (1988) J. Bacteriol., in press). Repeat B (75 bp x 3.6, in the center of smp5) is also present in the M6, but not in the M24 gene. Repeat C (105 bp x 2.7, just distal to the B repeats) shares homology with repeats in both the M6 and M24 genes. All three genes share extensive homology in their 3'-halves and in 5' sequences encoding the N-terminal signal peptides, but between these two regions there are highly variable sequences that are responsible for antigenic diversity. These relationships suggest that both intergenic and intragenic recombination has occurred during the evolution of distinct M protein serotypes. All three M proteins contain conserved hydrophobic and proline-rich sequences at their C-terminal ends, suggestive of a membrane anchor and a peptidoglycan spanning region.


Pelvic lymph node displacement in high-risk prostate cancer patients treated with image guided intensity modulated radiation therapy with 2 independent target volumes.
To evaluate the displacement of the pelvic lymph node (PLN) target when using cone beam computed tomography (CBCT) for localization of the prostate in patients treated with simultaneous integrated boost. High-risk prostate cancer patients treated with image guided intensity modulated radiation therapy with simultaneous integrated boost receiving 60 Gy in 20 fractions to the prostate and proximal seminal vesicles (PTV60) and 44 Gy in the same 20 fractions to the PLN (PTV44) were studied. Two hundred weekly CBCTs of 50 patients were retrospectively reviewed to assess the displacement of the iliac vessels compared with the simulation computed tomography. For each CBCT, possible displacements were analyzed at 3 levels of PTV44: a superior, middle, and inferior slice, making a total of 600 slices reviewed. Geographical miss (GM) was defined when any part of the iliac vessels on the CBCT was outside of the PTV44 contour. GM was found in 7 of the 600 CBCT slices, all in different patients. All GMs were of ≤5 mm. Four GMs occurred on the middle slice and 3 on the superior slice. In 3 cases, the GM was related to shifts ≥7 mm applied to the prostate. Our review suggests that for high-risk prostate cancer, the chance of not appropriately covering the PLN target after adjusting the prostate is low. GM was uncommon and in the order of only a few millimeters when it occurred.


Characteristics of indoor air pollution and estimation of respiratory dosage under varied fuel-type and kitchen-type in the rural areas of Telangana state in India.
Indoor Air Pollution (IAP) is one of the top environmental risks in developing countries including India, with more than a million deaths annually, predominantly through Particulate Matter (PM) exposure. The current study deals with the measurement of PM concentrations in rural households under varied fuel and kitchen-types, evaluation of the indoor air pollution (IAP) characteristics and estimation of respiratory dosage for the different subjects (women, young children and the elderly). Monitoring of particulate matter (PM) was carried out during summer, monsoon and winter season with biomass, LPG and combine of biomass and LPG being used as fuel for cooking. Furthermore, different types of indoor kitchens (with partition and without partition) and outdoor kitchens (separate enclose kitchen and open kitchen) were also considered as kitchen type along with fuel are two crucial factors contributing to IAP. Deposition fractions were calculated using Multiple Particle Path Dosimetry (MPPD) to study the deposition patterns in different parts of the human respiratory tract (HRT) - head, tracheobronchial and pulmonary for women, young children and the elderly people. Dosage of particulate matter was calculated by inputting the recorded PM measurements, a comparison made for biomass-LPG and dosage intensification due to the kitchen-type presented. While the biomass households exhibited high levels of dosage (1181.4 to 5891.7 μg) against the LPG households (89.9 to 811.2 μg), the indoor kitchen types exhibited a maximum intensification of 10.6 times than outdoor kitchens with the same fuel. This study not only establishes the IAP characteristics but also quantifies the role of fuel-type and kitchen-type in IAP. The study also indicates various measures that could be deployed to reduce dosage and thus minimize the health risks.


Breast cancer screening in England and the United States: a comparison of provision and utilisation.
Comparing breast cancer screening across countries within the context of some of the benefits and harms offers the opportunity to improve effectiveness through mutual learning. This paper describes the provision of breast cancer screening in England and the United States. The various recommendations for accessing breast cancer screening in the two countries are set out and the organisation of services including quality assurance, incentives and performance mechanisms considered. In the United States, younger women are routinely screened; they are less likely to benefit and more likely to be harmed. The utilisation of breast cancer screening amongst eligible women is broadly comparable in the two countries. However, there are differences in technical performance; the reasons for these including radiological reading procedures and cultural factors are explored. Despite a well-functioning screening programme, breast cancer mortality and survival in England are poor relative to other countries. Emphasis for American improvement should be on reducing false-positive recall rates, while the English NHS could supplement existing efforts to understand and improve comparatively poor survival and mortality.


Visual estimation versus quantitative assessment of left ventricular ejection fraction: a comparison by cardiovascular magnetic resonance imaging.
The aim of this study was to compare the visual and quantitative assessment for left ventricular ejection fraction (LVEF) in normal subjects and patients with impaired LV function. One hundred subjects (40 normal subjects, 40 patients with ischemic cardiomyopathy, and 20 patients with nonischemic cardiomyopathy) were investigated using a 1.5-T cardiovascular magnetic resonance imager. Images were acquired by a fast gradient-echo sequence with steady-state free precession using the standard short-axis method. Left ventricular EF was calculated from the sums of the outlined areas using the Simpson rule. Interobserver variability between the calculated and the visual EF was assessed. Analyses were performed randomly and blinded by 2 independent observers. Left ventricular EF was significantly underestimated by the visual read in all 3 groups (mean difference: normal subjects -2.6% +/- 2.6%, ischemic cardiomyopathy -1.7% +/- 2.1%, and nonischemic cardiomyopathy -1.2% +/- 2.1%; P < or = .02). The difference was larger in normal subjects than in patients with cardiomyopathy (P = .04). The interobserver variability was smaller for the quantitative assessment than for the visual estimation. Left ventricular EF is underestimated by visual estimation compared with the quantitative assessment. The visual approach for EF assessment may be used for rapid assessment of left ventricular function in clinical practice where accuracy is of less concern. For most accurate analysis, the quantitative standard short axis approach is required.


Biochemical and histopathologic comparison between blood and saline storage of canine veins.
Patency of vein grafts may be influenced by the medium in which they are stored temporarily. We compared saline solution vs blood on prostanoid production and maintenance of endothelium in canine veins after 1 hour of storage at 23 degrees C with 0.2 mg/ml of papaverine. Spontaneous and arachidonate-stimulated prostaglandin levels were measured by radioimmunoassay. Endothelial integrity was analyzed by light and electron microscopy. Prostaglandin production in blood vs that in saline solution was 1821 +/- 1264 and 1259 +/- 719 pg/cm2/min at control and 6705 +/- 3702 vs 6264 +/- 3409 pg/cm2/min, respectively, after stimulation. There were no statistically significant differences between the groups at any time point. Thromboxane levels were also indistinguishable between groups. Microscopy revealed 70% endothelial loss in blood vs 95% for saline solution. We conclude that endothelial preservation is enhanced by blood storage, that the medial layer produces substantial amounts of prostacyclin, and that additional storage solutions need to be investigated.


VWF attributes--impact on thrombus formation.
At sites of vascular injury, free-flowing platelets attach to the vessel wall to initiate thrombus formation in areas of high haemodynamic shear stress, a process that is critical for both haemostasis and thrombosis. This reaction is mediated by the binding of the platelet glycoprotein (GP) Iba to the A1 domain of immobilized von Willebrand factor (VWF), resulting in a complex series of events that includes platelet adhesion, activation and aggregation. Under elevated rates of shear stress these events support the formation of platelet-derived tethers and microparticles (MPs), which contain adhesive receptors and glycoproteins, and can bind to immobilized and soluble VWF, thereby facilitating thrombus formation. Understanding of the unique functional attributes of VWF has helped elucidate the interaction between VWF and platelets and its subsequent impact on thrombus formation. This interaction is multifaceted and modulated by different environmental conditions. A novel mechanism for initiating thrombus formation under high haemodynamic forces has recently been demonstrated. Results from direct real-time visualization of blood flow studies demonstrate activation-independent platelet aggregation, which occurs exclusively through binding of soluble VWF to platelet GPIb at very high shear stress, and may thus contribute to acute thrombotic occlusion. This article reviews the attributes of VWF and their impact on thrombus formation.


Comparative studies on the detection of mycotoxins in barley using enzyme immunoassays.
Barley samples (n = 128) from Central Canada (Manitoba) of the 1993 and 1994 crop years were analysed using enzyme immunoassays for the detection of the mycotoxins deoxy-nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, and zearalenone. For this study enzyme immunoassays, which were developed at the Lehrstuhl für Hygiene und Technologie der Milch as well as a commercial testkit (Ridascreen® DON, specific for deoxynivalenol and its acetylated derivatives) were used. In addition, some samples were analysed by using a combination of HPLC and enzyme immunoassay (immunochromatography). Results obtained by the enzyme immunoassays for these samples were compared with other analytical data on mycotoxin contamination (analysed by GC/MS) and with the mycological conditions, respectively.


Surgery in recurrent malignant melanoma.
Seventy-nine consecutive patients with resectable, recurrent malignant melanoma were treated with surgical excision, followed by adjuvant chemotherapy. Of 7 Stage IIIA patients, 6 remain alive; 5 are disease-free at 27 months. Of 33 patients with advanced stage IIIB disease with fixed tumor masses, including 16 cases that involved two nodal groups, 10 patients (30%) remain disease-free at 30 months. Of 12 Stage IIIAB patients, one remains disease-free at 26 months. Of 27 Stage IV patients, 7 (25%) remain disease-free at 36 months. Characteristic of those patients who remain disease-free is the initial presence of 3 or less discrete metastatic lesions, and a long prior disease-free interval. Surgical removal of metastatic lesions of malignant melanoma, in combination with chemotherapy, offers improved palliation in patients with a small number of metastatic lesions and a long previous disease-free interval.


Malakoplakia of prostate gland.
Malakoplakia of the prostate gland has rarely been reported. Its presentation often mimics carcinoma of the prostate. We report a case in a sixty-three-year-old patient who had a previous history of other granulomatous disease.


In situ modification of activated carbons developed from a native invasive wood on removal of trace toxic metals from wastewater.
Activated carbons were developed by phosphoric acid activation of sawdust from Prosopis ruscifolia wood, an indigenous invasive species of degraded lands, at moderate conditions (acid/precursor ratio=2, 450 degrees C, 0.5h). For in situ modification of their characteristics, either a self-generated atmosphere or flowing air was used. The activated carbons developed in the self-generated atmosphere showed higher BET surface area (2281m2/g) and total pore volume (1.7cm3/g) than those obtained under flowing air (1638m2/g and 1.3cm3/g). Conversely, the latter possessed a higher total amount of surface acidic/polar oxygen groups (2.2meq/g) than the former (1.5meq/g). To evaluate their metal sorption capability, adsorption isotherms of Cu(II) ion from model solutions were determined and properly described by the Langmuir model. Maximum sorption capacity (Xm) for the air-derived carbons (Xm=0.44mmol/g) almost duplicated the value for those obtained in the self-generated atmosphere (Xm=0.24mmol/g), pointing to a predominant effect of the surface functionalities on metal sequestering behaviour. The air-derived carbons also demonstrated a superior effectiveness in removing Cd(II) ions as determined from additional assays in equilibrium conditions. Accordingly, effective phosphoric acid-activated carbons from Prosopis wood for toxic metals removal from wastewater may be developed by in situ modification of their characteristics operating under flowing air.


Comparison of gait between walking up and down an incline with a walking device in older adults.
To identify the gait differences between cane and rolling walker (RW) use on incline and how these walking devices were received and used, 26 qualified older adults walked randomly on downward and upward with a cane and a RW respectively. With the RW use, downward walking show a faster velocity, higher cadence, less stance time, bigger steps and strides than upward walking (p≤.05); but no differences were seen with cane use. When comparing walking between a RW and a cane, those using a cane had faster velocity, larger step and stride lengths (P≤.01) but only during the upward condition. Incline surface plays a critical role in gait differences when walking with walking device. Geriatric professionals need to know the changes in gait that result from the type of device being used and need to incorporate this knowledge in the education provided to older adults for proper use of a walking device.


Hepatic angiomyolipoma: radiologic and histopathologic correlation.
We present two cases of hepatic angiomyolipoma. Histologic analysis showed that mature adipose tissue occupied 79.0% of the area on the largest cut surface in the first case and 40.2% in the second case. We suggest that the difference in the ratio of adipose tissue volume to its distribution is reflected on diagnostic images.


Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.


Deuterium echo-planar spectroscopic imaging (EPSI) in the human liver in vivo at 7 T.
To demonstrate the feasibility of deuterium echo-planar spectroscopic imaging (EPSI) to accelerate 3D deuterium metabolic imaging in the human liver at 7 T. A deuterium EPSI sequence, featuring a Hamming-weighted k-space acquisition pattern for the phase-encoding directions, was implemented. Three-dimensional deuterium EPSI and conventional MRSI were performed on a water/acetone phantom and in vivo in the human liver at natural abundance. Moreover, in vivo deuterium EPSI measurements were acquired after oral administration of deuterated glucose. The effect of acquisition time on SNR was evaluated by retrospectively reducing the number of averages. The SNR of natural abundance deuterated water signal in deuterium EPSI was 6.5% and 5.9% lower than that of MRSI in the phantom and in vivo experiments, respectively. In return, the acquisition time of in vivo EPSI data could be reduced retrospectively to 2 min, beyond the minimal acquisition time of conventional MRSI (of 20 min in this case), while still leaving sufficient SNR. Three-dimensional deuterium EPSI, after administration of deuterated glucose, enabled monitoring of hepatic glucose dynamics with full liver coverage, a spatial resolution of 20 mm isotropic, and a temporal resolution of 9 min 50 s, which could retrospectively be shortened to 2 min. In this work, we demonstrate the feasibility of accelerated 3D deuterium metabolic imaging of the human liver using deuterium EPSI. The acceleration obtained with EPSI can be used to increase temporal and/or spatial resolution, which will be valuable to study tissue metabolism of deuterated compounds over time.


[Expression of gastrin and gastrin releasing peptide in patient's with gastric cancer by using tissue chip technique].
To study the expression of gastrin(GAS) and gastrin releasing peptide(GRP) in patients with gastric cancer and investigate the clinical significance. The expression of GAS and GRP in sixty patients with gastric cancer was detected by using tissue chip technique and immunohistochemical methods. The positive rates of GAS and GRP were 30.0% and 11.7% respectively in 60 cases with gastric cancer. The positive rates of GAS and GRP were higher in moderately and poorly differentiated cancers than those in well differentiated cancer (P< 0.05). The positive rates of GAS and GRP were significantly higher in mucinous adenocarcinoma and signet-ring cell carcinoma than those in other types of gastric cancer (P< 0.05). The positive expression of GAS and GRP in gastric cancer was correlated with lymph node metastasis (P< 0.05). Tissue chip technique is a feasible,rapid,economic and accurate approach for screening clinical tissue specimens on a large scale.


Alterations in Oral Microbiota in HIV Are Related to Decreased Pulmonary Function.
Rationale: Mechanisms of HIV-associated chronic obstructive pulmonary disease (COPD) are poorly understood. The oral microbiome shapes the lung microbiome, and gut dysbiosis can affect lung diseases; however, relationships of the oral and gut microbiome to COPD in HIV have not been explored.Objectives: To examine alterations in the oral and gut microbiome associated with pulmonary disease in persons with HIV (PWH).Methods: Seventy-five PWH and 93 HIV-uninfected men from the MACS (Multicenter AIDS Cohort Study) performed pulmonary function testing. Sequencing of bacterial 16S ribosomal RNA in saliva and stool was performed. We used nonmetric multidimensional scaling, permutational multivariate ANOVA, and linear discriminant analysis to analyze communities by HIV and lung function.Measurements and Main Results: Oral microbiome composition differed by HIV and smoking status. Alterations of oral microbial communities were observed in PWH with abnormal lung function with increases in relative abundance of Veillonella, Streptococcus, and Lactobacillus. There were no significant associations between the oral microbiome and lung function in HIV-uninfected individuals. No associations with HIV status or lung function were seen with the gut microbiome.Conclusions: Alterations of oral microbiota in PWH were related to impaired pulmonary function and to systemic inflammation. These results suggest that the oral microbiome may serve as a biomarker of lung function in HIV and that its disruption may contribute to COPD pathogenesis.


Hybrids of RNA viruses and viroid-like elements replicate in fungi.
Earth's life may have originated as self-replicating RNA, and it has been argued that RNA viruses and viroid-like elements are remnants of such pre-cellular RNA world. RNA viruses are defined by linear RNA genomes encoding an RNA-dependent RNA polymerase (RdRp), whereas viroid-like elements consist of small, single-stranded, circular RNA genomes that, in some cases, encode paired self-cleaving ribozymes. Here we show that the number of candidate viroid-like elements occurring in geographically and ecologically diverse niches is much higher than previously thought. We report that, amongst these circular genomes, fungal ambiviruses are viroid-like elements that undergo rolling circle replication and encode their own viral RdRp. Thus, ambiviruses are distinct infectious RNAs showing hybrid features of viroid-like RNAs and viruses. We also detected similar circular RNAs, containing active ribozymes and encoding RdRps, related to mitochondrial-like fungal viruses, highlighting fungi as an evolutionary hub for RNA viruses and viroid-like elements. Our findings point to a deep co-evolutionary history between RNA viruses and subviral elements and offer new perspectives in the origin and evolution of primordial infectious agents, and RNA life.


Motivation to modify lifestyle risk behaviors in women treated for breast cancer.
To determine motivators of health behaviors (relevant to risk for chronic disease and cancer recurrence) after a cancer diagnosis. Eighty-six women who had been treated for breast cancer (mean age, 54.8 years; median time since diagnosis, 23.5 months) participated in this cross-sectional study (1997-1998). Respondents completed a questionnaire assessing overweight or obesity status, dietary fat intake, energy expenditure, motivational readiness for exercise and weight loss, and variables associated with readiness for exercise adoption and weight loss. Forty-six women (54%) were overweight or obese, and 47 women (55%) reported dietary fat intake of 30% or higher. Sixty-one women (72%) were in action/ maintenance stages for exercise adoption. A majority believed that diet and exercise can change the course of cancer. Overweight and obese women in the sample were more likely to be in early stages of motivational readiness for weight loss, and they reported significantly lower exercise self-efficacy and lower eating self-efficacy than their nonoverweight peers. However, they endorsed more benefits associated with weight loss than the nonoverweight subgroup. Thirty-three women (39%) reported both a low-fat diet and exercising at recommended levels. Only a minority of respondents reported consuming a diet low in fat and exercising at recommended levels, which suggests a need to improve both diet and exercise behaviors among women treated for breast cancer. Overweight and obese women reported low self-efficacy for exercise and eating, suggesting that interventions should focus on increasing self-efficacy for behavior change.


Gleno-humeral joint in the chimpanzee: comparative anatomical analysis for use in endoprosthetic replacement.
The gleno-humeral joint of the adult chimpanzee is morphologically compared to the human shoulder to assess the feasibility of this animal for use in experimental prosthetic replacement. The anatomical structure appears similar enough to man to warrant investigation of this animal as a vehicle for experimental implant design in the shoulder. Several anatomical structural differences were noted which necessitated modification of the fixturing segments of a "Floating Socket" total gleno-humeral endoprosthesis.


Selenoprotein N is an endoplasmic reticulum calcium sensor that links luminal calcium levels to a redox activity.
The endoplasmic reticulum (ER) is the reservoir for calcium in cells. Luminal calcium levels are determined by calcium-sensing proteins that trigger calcium dynamics in response to calcium fluctuations. Here we report that Selenoprotein N (SEPN1) is a type II transmembrane protein that senses ER calcium fluctuations by binding this ion through a luminal EF-hand domain. In vitro and in vivo experiments show that via this domain, SEPN1 responds to diminished luminal calcium levels, dynamically changing its oligomeric state and enhancing its redox-dependent interaction with cellular partners, including the ER calcium pump sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). Importantly, single amino acid substitutions in the EF-hand domain of SEPN1 identified as clinical variations are shown to impair its calcium-binding and calcium-dependent structural changes, suggesting a key role of the EF-hand domain in SEPN1 function. In conclusion, SEPN1 is a ER calcium sensor that responds to luminal calcium depletion, changing its oligomeric state and acting as a reductase to refill ER calcium stores.


Temporal and spatial pattern of common tern (Sterna hirundo) foraging in the Wadden Sea.
In 1989, 313 foraging flights of common terns in the Wadden Sea were radio-tracked. The feeding trips lasted on average 115 min covering about 30 km per flight. Completely tracked flights had a mean radius of 6.3 km. The terns preferred distinct foraging areas in the Wadden Sea. These were visited at site-specific phases of the tidal cycle resulting in a temporal and spatial pattern of foraging, caused by the site-specific and tide-related fluctuations of food availability.


Deletion of p21/Cdkn1a confers protective effect against prostate tumorigenesis in transgenic adenocarcinoma of the mouse prostate model.
Cyclin-dependent kinase inhibitors (CDKIs) p21(Cip1/Waf1) (p21) and p27(Kip1) (p27) play a determining role in cell cycle progression by regulating CDK activity; however, p21 role in prostate cancer (PCa) is controversial. Whereas p21 upregulation by anticancer agents causes cell cycle arrest in various PCa cell lines, elevated p21 levels have been associated with higher Gleason score, poor survival and increased PCa recurrence. These conflicting findings suggest that more studies are needed to examine p21 role in PCa. Herein, employing genetic approach, transgenic mice harboring p21/Cdkn1a homozygous deletion (p21(-/-)) were crossed with the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice to characterize in vivo consequences of p21 deletion on prostate tumorigenesis. Lower urogenital tract weight of p21(-/-)/TRAMP mice was significantly lower than those of p21(+/-)/TRAMP and TRAMP mice. Histopathology further supported these observations, showing less aggressiveness in prostates of p21(-/-)/TRAMP. Furthermore, a significantly higher incidence of low-grade prostatic intraepithelial lesions (PIN) with a concomitant reduction in adenocarcinoma incidence was observed in p21(-/-)/TRAMP mice compared with TRAMP mice. In addition, whereas TRAMP mice showed the presence of poorly differentiated adenocarcinoma lesions, no such lesions were observed in p21/TRAMP transgenic mice. Specifically, there was a significant reduction in the severity of lesions in both p21(-/-)/TRAMP and p21(+/-)/TRAMP mice compared with TRAMP mice. Together, our data showed that p21 deletion reduces prostate tumorigenesis by slowing-down progression of PIN (pre-malignant) to adenocarcinoma (malignant), suggesting that intact p21 expression is associated with PCa aggressiveness, while its decreased levels may in fact confer protection against prostate tumorigenesis.


Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C.
The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.


Mitochondrial Metabolism in Hibernation: Regulation and Implications.
Hibernators rapidly and reversibly suppress mitochondrial respiration and whole animal metabolism. Posttranslational modifications likely regulate these mitochondrial changes, which may help conserve energy in winter. These modifications are affected by reactive oxygen species (ROS), so suppressing mitochondrial ROS production may also be important for hibernators, just as it is important for surviving ischemia-reperfusion injury.


[Results obtained using various types of suture material in laparotomy and the treatment of umbilical hernia in horses (author's transl)].
Comparative studies were done on healing of the wound following laparotomy through the ventral wall of the abdomen (paramedian incision or in the linea alba) in seventy horses and following surgical treatment of umbilical hernia in eighty-five (young) horses, in which perlon, (chromic) catgut, stainless steel wire and polyglycollic acid were used as suture material. Though with some reserve, as the study was concerned with the comparison of findings in clinical cases in which a number of conditions may vary, it is concluded that steel wire and polyglycollic acid are preferable to perlon and (chromic) catgut in suturing the abdominal wall and hernial ring in horses.


In vitro study of a novel multi-substituted hydroxyapatite nanopowder synthesized by an ultra-fast, efficient and green microwave-assisted method.
In order to improve the biological activity of hydroxyapatite (HA), a multi-substituted HA (SHA) nanopowder with the chemical composition of Ca9.5Mg0.25Sr0.25(PO4)5.5(SiO4)0.5(OH)1.2F0.8 was synthesized using the microwave-assisted method. X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) revealed that all ions were substituted in the HA crystal lattice. The HA and SHA nanoparticles had a semi-spherical morphology with the average size of 90 and 80 nm, respectively. In-vitro bioactivity assessments showed that after the 28-day immersion of the samples in the simulated body fluid, the morphology of the precipitated apatites on the surface of the HA sample still consisted of spherical particles with a cauliflower-like structure. However, in the SHA sample, the morphology of the precipitated apatites was changed to a nanorod-like one similar to the bone-like apatite, which may be attributed the presence of Sr in the precipitated apatites. The results showed that the release of the substituted ions not only had no adverse effect on the cell viability and cell attachment, but also enhanced the alkaline phosphatase activity of MG63 osteoblast like cells in the SHA group, as compared to the HA and control groups. The results indicated that the simultaneous substitution of Si, Mg, Sr, and F in HA nanoparticles could effectively promote bioactivity, cell proliferation and differentiation. This novel HA composition could be, therefore, well used for implant coating, bone tissue engineering and other orthopedic applications.


Purpurogallin: in vivo evidence of a novel and effective cardioprotector.
We observed that purpurogallin (PPG) which is a flavonoid markedly protects the rabbit against myocardial ischemia-reperfusion injury. In rabbits undergoing 1-h ligation of the anterior ventricular coronary artery, a bolus infusion of PPG was introduced into the post-ischemic heart immediately before 3-h reperfusion. Against negligible necrosis in 6 sham-operated controls, and 41.7 (SD 11.3)% necrosis in the area at risk for the placebo control group (n = 14 animals), the PPG-treated groups (n = 6, 6, 14) had a necrosis of 26.8 (6.4)%, 10.8 (3.5)%, and 11.7 (5.2)% at doses of 2.5, 5, and 10 mumol/kg, respectively (each with p < 0.01 vs control value). By comparison, infusion of Trolox (a vitamin E analogue) at 5 mumol/kg produced a higher necrosis of 17.7 +/- 7.2% (n = 6, p < 0.05 vs value obtained from 5 mumol/kg PPG-treated group) in the same model. Note that myocardial necrosis was estimated by tetrazolium-based histochemistry and confirmed by light and transmission electron microscopies. These data support our contention that PPG is an effective cardioprotector, whose mechanism of action will be reported separately.


Migration of superior vena cava stent.
There has been a recent increase in the use of endovascular prostheses resulting in complex surgical and interventional complications not previously recognised. We report a case of Superior vena cava stenosis treated with a wallstent which migrated to the right atrium, necessitating a combined radiological and surgical approach to retrieve it.


Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event.
Posttraumatic stress disorder (PTSD) is a psychiatric condition that is directly precipitated by an event that threatens a person's life or physical integrity and that invokes a response of fear, helplessness, or horror. In recent years it has become clear that only a proportion of those exposed to fear-producing events develop or sustain PTSD. Thus, it seems that an important challenge is to elucidate aberrations in the normal fear response that might precipitate trauma-related psychiatric disorder. This paper summarizes the findings from recent studies that examined the acute and longer term biological response to traumatic stress in people appearing to the emergency room immediately following trauma exposure. In the aggregate, these studies have demonstrated increased heart rate and lower cortisol levels at the time of the traumatic event in those who have PTSD at a follow-up time compared to those who do not. In contrast, certain features associated with PTSD, such as intrusive symptoms and exaggerated startle responses, are only manifest weeks after the trauma. The findings suggest that the development of PTSD may be facilitated by an atypical biological response in the immediate aftermath of a traumatic event, which in turn leads to a maladaptive psychological state.


Monitoring of Levamisole Concentration in Serum of Traffic Participants after Cocaine Consumption.
This study highlights the problem of levamisole-adulterated cocaine in context of active traffic participation. For the purposes of levamisole concentration monitoring in human serum, an analytical method based on LC-MS/MS and solid-phase extraction was applied. A Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm column and a mobile phase consisting of A (H2 O/methanol = 95/5, v/v) and B (H2 O/methanol = 3/97, v/v), both with 10 mM ammonium acetate and with 0.1% acetic acid (pH = 3.2), were used. The validation experiments demonstrated that the method applied was appropriate for levamisole quantification in human serum. For 23% of levamisole-positive samples, the concentrations exceeded 20 ng/mL. Therefore, the interaction of this drug with cocaine has to be considered as important for active traffic participation. As a consequence, monitoring of levamisole concentration in human serum is recommended, as long as it is used as cocaine adulterant.


Monkeypox Virus: A Comprehensive Overview of Viral Pathology, Immune Response, and Antiviral Strategies.
The years 2022-2023 witnessed a monkeypox virus (mpox) outbreak in some countries worldwide, where it exists in an endemic form. However, the number of infectious cases is continuously on the rise, and there has been an unexpected, drastic increase in cases that result from sustained transmission in non-endemic regions of the world. Under this scenario, it is pertinent for the world to be aware of healthcare threats to mpox infection. This review aimed to compile advanced data regarding the different aspects of mpox disease. A comprehensive strategy for the compilation of recent data was adopted to add data regarding mpox, biology, viral pathology, immune response, and brief details on the antiviral strategies under trial; the search was limited to 2016-2023. The aim is to make the scientific community aware of diverse aspects of mpox. Consequently, detailed insights have been drawn with regard to the nature, epidemiology, etiology, and biological nature of mpox. Additionally, its host interaction and viral infectious cycle and immune interventions have been briefly elaborated. This comprehensively drawn literature review delivers brief insights into the biological nature, immune responses, and clinical developments in the form of therapeutics against mpox. This study will help scientists understand the biological nature and responses in hosts, which will further help clinicians with therapeutic handling, diagnosis, and treatment options. This study will provide updated information on mpox's pathology, immune responses, and antiviral strategies. Moreover, it will also help the public to become educated on the healthcare-associated threat and take timely mitigation measures against expected mpox outbreaks in the future.


Wound healing effect of flavonoid rich fraction and luteolin isolated from Martynia annua Linn. on streptozotocin induced diabetic rats.
To evaluate wound healing potential of flavonoid fractions of Martynia annua (M. annua) Linn. leaves in diabetic rats on the basis of folkloric information and preliminary study. The flavonoid compound luteolin and apigenin were isolated from dried leaves of plant by column chromatography. The two concentrations (0.2% and 0.5% w/w) of luteolin and flavonoid fraction were selected for topically applied as ointment on diabetic wound. The Povidone Iodine Ointment USP was used as a reference. On 18th days, protein content, hydroxyproline and antioxidants (SOD, CAT and GSH) level in granuloma tissues were determined. The results showed that, percent wound contraction were observed significantly (P<0.01) greater in MAF fraction and 0.5% w/w of luteolin treatment groups. Presence of matured collagen fibres and fibroblasts with better angiogenesis were observed in histopathological studies. In conclusion, our findings suggest that flavonoid fraction (MAF) and luteolin (0.5% w/w) may have potential benefit in enhancing wound healing in diabetic condition, possibly due to free-radical scavenging activity of plant.


The protective effects of lactoferrin against murine norovirus infection through inhibition of both viral attachment and replication.
The purpose of this study was to evaluate the effects of bovine lactoferrin against norovirus infection using mouse norovirus (MNV) and Raw264.7 cell in vitro. When Raw264.7 cells were infected with MNV in the presence or absence of lactoferrin, the cytotoxic damage to the infected Raw264.7 cells significantly and dose-dependently decreased and completely inhibited in the presence of 15 or 20 μg/well of lactoferrin as compared with the absence of lactoferrin. Correspondingly, the MNV titers in the culture medium and intracellularly were significantly decreased in infected Raw264.7 cells treated with lactoferrin compared to control infected Raw264.7 cells. The mechanisms responsible for the protective effects of lactoferrin against MNV infection were attributed to both its inhibition of the initial MNV attachment to cells and the subsequent interference with MNV replication. Moreover, it was revealed that lactoferrin could rapidly induce the expression of anti-viral cytokine mRNA, such as IFN-α and IFN-β which involved in inhibition of MNV replication in infected Raw264.7 cells, in the early phase of infection. It was concluded that lactoferrin exerts protective effects against MNV infection through inhibition of both viral attachment and replication. The present results provide evidence that lactoferrin may be useful as a preventive and/or therapeutic anti-norovirus agent.


New understanding of the pathogenesis and treatment of stroke-related sarcopenia.
Sarcopenia is a syndrome characterized by progressive systemic muscle loss and decreased function. The loss of systemic muscle mass and decreased function after stroke can't be explained by brain injury alone, and it is considered to be a kind of secondary sarcopenia, which is called stroke-related sarcopenia. More and more evidence shows that stroke-related sarcopenia can promote the occurrence and development of sarcopenia through a variety of pathogenesis, such as immobilization, impaired feeding, sympathetic activation, inflammation and denervation. Post-stroke disability brings difficulties to the screening and diagnosis of sarcopenia. Simple and easy rehabilitation scores and clinical tests can be used for the determination of body function under specific conditions of stroke, as well as for the screening stroke-related sarcopenia. At present, there is still no particularly effective way to stop its progress,however, the combination of rehabilitation exercise, nutrition supply and drugs may delay or even prevent the development of stroke-related sarcopenia. This article reviews the latest progress in the pathogenesis, screening, evaluation and treatment of stroke-related sarcopenia to provide reference for clinical treatment and rehabilitation of stroke.


Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells.
Ndrg2 is a member of the N-myc downstream-regulated genes. Thus far, two different isoforms of rat Ndrg2 protein, Ndrg2S and Ndrg2L, have been identified. Recently, we have identified rat Ndrg2 as a novel target molecule of antidepressants and ECT. The functional role of Ndrg2 in the central nervous system, however, remains unclear. In the present study, we examined the expression of endogenous Ndrg2, cellular localization of transfected Ndrg2 protein, and morphological changes resulting from overexpression of Ndrg2 in NGF-differentiated PC12 cells. Neurites began to sprout 1-2 days after exposure to NGF; subsequent neurite growth continued for 5 days. During this time, we evaluated Ndrg2 mRNA expression by real-time quantitative PCR and found that expression significantly increased in a time-dependent manner. Interestingly, V5-conjugated Ndrg2S and Ndrg2L proteins expressed in NGF-differentiated PC12 specifically localized to cell surface membranes and growth cones. Moreover, Ndrg2S and Ndrg2L overexpression promoted neurite elongation in NGF-differentiated PC12 cells. In conclusion, our findings offer novel insights into the physiological roles of Ndrg2 in the central nervous system.


Vasoactive intestinal peptide in the normal and inflamed feline gallbladder.
Intravenous infusion of vasoactive intestinal peptide (VIP) causes gallbladder mucosal fluid secretion by an action on epithelial cell receptors in the cat. Gallbladder fluid secretion is observed also in experimental cholecystitis and this secretion is abolished when the intramural gallbladder nerves are blocked. In the present study, immunoreactive VIP was detected in the gallbladder contents (29 +/- 5 (S.E.M.) pM) in the obstructed lumen of the gallbladder in cats with experimental cholecystitis and gallbladder mucosal fluid secretion, but not in the normal feline gallbladder. During luminal perfusion of the gallbladder in vivo, the calculated secretion of VIP into the gallbladder lumen in animals with experimental cholecystitis was significantly higher (0.31 +/- 0.08 (S.E.M.), pmol/h) than in controls (0.11 +/- 0.02 (S.E.M.), pmol/h) while plasma levels of VIP were similar. Recovery of exogenously administered VIP was similar in normal and inflamed gallbladders. The present results support the hypothesis that intramural VIP-releasing nerve fibers may be activated in cholecystitis.


Unlocking grapevine in vitro regeneration: Issues and perspectives for genetic improvement and functional genomic studies.
In vitro plant regeneration is a pivotal process in genetic engineering to obtain large numbers of transgenic, cisgenic and gene edited plants in the frame of functional gene or genetic improvement studies. However, several issues emerge as regeneration is not universally possible across the plant kingdom and many variables must be considered. In grapevine (Vitis spp.), as in other woody and fruit tree species, the regeneration process is impaired by a recalcitrance that depends on numerous factors such as genotype and explant-dependent responses. This is one of the major obstacles in developing gene editing approaches and functional genome studies in grapevine and it is therefore crucial to understand how to achieve efficient regeneration across different genotypes. Further issues that emerge in regeneration need to be addressed, such as somaclonal mutations which do not allow the regeneration of individuals identical to the original mother plant, an essential factor for commercial use of the improved grapevines obtained through the New Breeding Techniques. Over the years, the evolution of protocols to achieve plant regeneration has relied mainly on optimizing protocols for genotypes of interest whilst nowadays with new genomic data available there is an emerging opportunity to have a clearer picture of its molecular regulation. The goal of this review is to discuss the latest information available about different aspects of grapevine in vitro regeneration, to address the main factors that can impair the efficiency of the plant regeneration process and cause post-regeneration problems and to propose strategies for investigating and solving them.


Sex-specific regulation of immune responses by PPARs.
The prevalence of autoimmune, infectious and metabolic diseases is different for men and women owing to the respective ability of their immune systems to respond to self and foreign antigens. Although several factors, including hormones and the X-chromosome, have been suggested to contribute to such sex-specific immune responses, the underlying factors remain poorly defined. Recent studies using peroxisome proliferator-activated receptor (PPAR) ligands and knockout mice have identified sex-dimorphic expression of PPARs, and have shown that the inhibitory functions of PPAR in T cells are substantially affected by the sex hormones. In this review, we consider the sex-specific differences in PPARs and summarize the diverse PPAR-mediated, sex-specific properties of effector T-cell responses, such as T-cell activation, survival and differentiation, as well as their involvement in T-cell-related autoimmune diseases, including colitis, graft-versus-host disease and experimental autoimmune encephalomyelitis. Understanding PPAR-mediated sex differences in immune responses will provide more precise insights into the roles of PPARs in effector T cells.


The Challenges of Using MRI During Radiotherapy.
In this article we aim to introduce the main considerations in integrating magnetic resonance imaging (MRI) into the radiotherapy workflow. We will cover the use of MRI for improved delineation, considerations regarding MRI-only workflows, and the potential of functional imaging techniques. The challenges of implementing each of these will be discussed to ensure safe usage in radiotherapy.


Oligo(U) sequences present in sea urchin maternal RNA decrease following fertilization.
Oligo(U) tracts were identified and measured in RNA from sea urchin eggs and embryos using a quantitative assay based on the amount of [3H]poly(A) protected from RNase T2 in duplexes with the oligo(U). The oligo(U) amounted to 0.0035% of egg RNA (0.063 X 10(-12) g/egg) and decreased to 0.0015% (0.027 X 10(-12) g/embryo) by 2 hr after fertilization. The oligo(U) tracts had a maximum size of 15-30 nucleotides and were associated with two size classes of RNA. In eggs about half were in 100 to 200 nucleotide RNA and half in mRNA-sized molecules. After fertilization, the oligo(U) in the population of large-mRNA-sized molecules was greatly reduced.


Oxidative stress in patients undergoing high-dose chemotherapy plus peripheral blood stem cell transplantation.
Chemotherapy and radiation therapy are associated with increased formation of reactive oxygen species and depletion of critical plasma and tissue antioxidants. In patients undergoing high-dose chemotherapy, the plasma antioxidant concentration has been shown to decrease. However, these studies in which the oxidative stress status were investigated have a small number of patients and they are heterogeneous. In this study, the changes in certain trace elements together with oxidative stress parameters were investigated in 36 patients who had undergone autologous stem cell transplantation because of solid and hematological malignancies. Blood samples of the patients were examined before the high-dose chemotherapy (baseline), before stem cell transplantation (day -1), and after stem cell transplantation on day 1, 3, and 6. Erythrocyte zinc, silver, and iron levels were measured by atomic absorption spectrophotometry; malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured by UV-vis spectrophotometry. After high-dose chemotherapy, significant increases in the levels of MDA, GSH-Px, and SOD were observed. On the other hand, Cu levels remained the same while the levels of erythrocyte Zn and Fe were increased. Significant correlation was observed among MDA, GSH-Px, and SOD (p<0.05). High-dose chemotherapy gives rise to an increase in the oxidative stress and the reactive oxygen species. Standard parenteral nutrition protocols were found to be insufficient to lower this stress.


[Imaging tumor vascularization of hepatocellular carcinoma with ultrasound angiography].
With the introduction, in 1994, of Ultrasound Angio (UA), a technical innovation in sonographic colour coded blood-flow detection has become available using angle-independent amplitude signal plotting leading to an enhanced sensitivity in blood flow detection. In a first application study we attempted to verify an improved blood-flow detection in hepatocellular carcinomas (HCC) compared to conventional colour coded duplex sonography. In all patients with HCC we found a highly improved detection of internal vascularity. In one patient, we could even detect blood flow in the tumour which was not visible with several other conventional highly sensitive colour duplex equipment.


Outcomes of preterm infants following the introduction of room air resuscitation.
After 2006 most neonatal intensive care units (NICUs) in Canada stopped initiating newborn resuscitation with 100% oxygen. In this retrospective cohort study, we compared neonatal outcomes in infants born at ≤ 27 weeks gestation that received <100% oxygen (OXtitrate group, typically 21-40% oxygen) during delivery room resuscitation to infants that received 100% oxygen (OX100 group). Data from 17 NICUs included 2326 infants, 1244 in the OXtitrate group and 1082 in the OX100 group. The adjusted odds ratio (AOR) for the primary outcome of severe neurologic injury or death was higher in the OXtitrate group compared with the OX100 group (AOR 1.36; 95% CI 1.11, 1.66). A similar increase was also noted when comparing infants initially resuscitated with room air to the OX100 group (AOR 1.33; 95% CI 1.04, 1.69). Infants in the OXtitrate group were less likely to have received either medical or surgical treatment for a patent ductus arteriosus (AOR 0.53; 95% CI 0.37, 0.74). In Canadian NICUs, we observed a higher risk of severe neurologic injury or death among preterm infants of ≤ 27 weeks gestation following a change in practice to initiating resuscitation with either room air or an intermediate oxygen concentration.


Use of ventricular assist device as bridge to simultaneous heart and kidney transplantation in patients with cardiac and renal failure.
Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.


A retrospective comparative analysis of factors affecting the decision and outcome of initial intravenous immunoglobulin alone or intravenous immunoglobulin plus methylprednisolone use in children with the multisystem inflammatory syndrome.
For children with the multisystem inflammatory syndrome(MIS-C), intravenous immunoglobulins (IVIG) with or without methylprednisolone are the most effective treatment. In this study, IVIG combined with methylprednisolone was compared to IVIG used alone in children with MIS-C. This retrospective cohort study was carried out between April 1, 2020, and November 1, 2021. This study covered all children with MIS-C. According to whether they received IVIG alone or IVIG with methylprednisolone as an initial treatment for MIS-C, the patients were split into two groups. The IVIG dosage for the patients in group I was 2 gr/kg, whereas the IVIG dosage for the patients in group II was 2 gr/kg + 2 mg/kg/day of methylprednisolone. These two groups were contrasted in terms of the frequency of fever, length of hospital stay, and admission to the pediatric intensive care unit. The study comprised 91 patients who were diagnosed with MIS-C and were under the age of 18. 42 (46.2%) of these patients were in the IVIG alone group (group I), and 49 (53.8%) were in the IVIG + methylprednisolone group (group II). Patients in group II had a severe MIS-C ratio of 36.7%, which was substantially greater than the rate of severe MIS-C patients in group I (9.5%) (p 0.01). When compared to group I (9.5%), the rate of hypotension was considerably higher in group II (30.6%) (p = 0.014). Additionally, patients in group II had considerably higher mean serum levels of C-reactive protein. The incidence of fever recurrence was 26.5% in group II and 33.3% in group I, however the difference was not statistically significant (p > 0.05). The choice of treatment for patients with MIS-C should be based on an individual evaluation. In MIS-C children with hypotension and/or with an indication for a pediatric intensive care unit, a combination of IVIG and methylprednisolone may be administered. For the treatment modalities of children with MIS-C, however, randomized double-blind studies are necessary.


Liver Transplantation for Budd-Chiari Syndrome With Large Solitary Focal Nodular Hyperplasia of the Liver in a Patient With Essential Thrombocythemia: Case Report. [Corrected].
Budd-Chiari syndrome is a rare condition caused by interrupted hepatic venous outflow in the hepatic veins, inferior vena cava, or right atrium. Reports from the literature have delineated on focal nodular hyperplasia (FNH)-like lesions in association with Budd-Chiari Syndrome. To our knowledge, there are no reports about true FNH lesions in patients with Budd-Chiari Syndrome. Focal nodular hyperplasia develops in disorders with aberrant circulation and vasculature. We report a case of Budd-Chiari syndrome in association with large solitary FNH in a 22-year-old man who was referred to our institution with sudden intermittent right upper quadrant abdominal pain, vomiting, diarrhea with pale stool, decreased appetite, dark urine, and abdominal distention for 15 days. Laboratory investigations revealed anemia, thrombocytosis, and abnormal liver function tests and coagulation profile. Imaging revealed hepatic vein thrombosis, confirming Budd-Chiari syndrome, and a 6.2 × 6.1 × 6.8 cm lesion in segment 8 of the liver. Primary cause of Budd-Chiari syndrome was essential thrombocythemia according to bone marrow biopsy and molecular testing results. The patient was treated medically and underwent transjugular intrahepatic portosystemic shunt insertion. The lesion in segment 8 continued to enlarge. Cadaveric liver transplantation was carried out. On gross and histologic examination of the explanted liver, the lesion was found to be a true FNH.


The association between endometriosis and risk of endometrial cancer and breast cancer: a meta-analysis.
Endometriosis (EMS) is confirmed pathophysiologically to be an estrogen-dependent disease, similar to endometrial hyperplasia/cancer and breast cancer. Epidemiological and biological data on endometriosis might explain links between endometriosis and these cancers. We sought to identify the differences in the risk of endometrial cancer and breast cancer between women with and women without endometriosis. We searched PubMed, EMBASE, the Cochrane Library, and four Chinese databases (CNKI, VIP, WanFang, CBM) to identify relevant studies published online between January 2011 and March 2021. In our meta-analysis, we used the Newcastle-Ottawa Scale (NOS) to evaluate the design and quality of all studies, and we calculated the pooled risk ratio (RR) using the random model. The Q test and I2 were used to evaluate the degree of heterogeneity of eligible studies. We used funnel plots and Begg's and Egger's tests to assess publication bias. Of the 1369 articles, we finally included 14 cohort studies and seven case-control studies. Data from large cohort and case-control studies indicate that women with endometriosis had an increased risk of both endometrial cancer [RR, 1.662; 95% CI, (1.148-2.407)] and breast cancer [RR, 1.082; 95% CI, (1.001-1.169)]. Endometriosis can increase the risk of endometrial cancer and breast cancer, and women with endometriosis are recommended to receive routine screening in long-term management.