Video Captioning with Object-Aware Spatio-Temporal Correlation and Aggregation.
Video captioning is a significant challenging task in computer vision and natural language processing, aiming to automatically describe video content by natural language sentences. Comprehensive understanding of video is the key for accurate video captioning, which needs to not only capture the global content and salient objects in video, but also understand the spatio-temporal relations of objects, including their temporal trajectories and spatial relationships. Thus, it is important for video captioning to capture the objects' relationships both within and across frames. Therefore, in this paper, we propose an object-aware spatio-temporal graph (OSTG) approach for video captioning. It constructs spatio-temporal graphs to depict objects with their relations, where the temporal graphs represent objects' inter-frame dynamics, and the spatial graphs represent objects' intra-frame interactive relationships. The main novelties and advantages are: (1) Bidirectional temporal alignment: Bidirectional temporal graph is constructed along and reversely along the temporal order to perform bidirectional temporal alignment for objects across different frames, which provides complementary clues to capture the inter-frame temporal trajectories for each salient object. (2) Graph based spatial relation learning: Spatial relation graph is constructed among objects in each frame by considering their relative spatial locations and semantic correlations, which is exploited to learn relation features that encode intra-frame relationships for salient objects. (3) Object-aware feature aggregation: Trainable VLAD (vector of locally aggregated descriptors) models are deployed to perform object-aware feature aggregation on objects' local features, which learn discriminative aggregated representations for better video captioning. A hierarchical attention mechanism is also developed to distinguish contributions of different object instances. Experiments on two widely-used datasets, MSR-VTT and MSVD, demonstrate our proposed approach achieves state-of-the-art performances in terms of BLEU@4, METEOR and CIDEr metrics.


Biologics registers in RA: methodological aspects, current role and future applications.
The beginning of the 21st century saw a biopharmaceutical revolution in the treatment of inflammatory rheumatic diseases, particularly rheumatoid arthritis. The fast-evolving use of biologic therapies highlighted the need to develop registers at national and international levels with the aim of collecting long-term data on patient outcomes. Over the past 15 years, many biologics registers have contributed a wealth of data and provided robust and reliable evidence on the use, effectiveness and safety of these therapies. The unavoidable challenges posed by the continuous introduction of new therapies, particularly with regard to understanding their long-term safety, highlights the importance of learning from experience with established biologic therapies. In this Perspectives article, the role of biologics registers in bridging the evidence gap between efficacy in clinical trials and real-world effectiveness is discussed, with a focus on methodological aspects of registers, their unique features and challenges and their role going forward.


Gorlin syndrome presenting as prenatal chylothorax in a girl.
Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome, is a rare autosomal dominant condition with an estimated prevalence of 1:57 000. GS is associated with congenital malformations and predisposition to neoplasms. The main features observed in patients with GS are basal cell carcinomas, odontogenic keratocysts, skeletal anomalies including scoliosis and bifid ribs, palmar and plantar epidermal cysts, facial dysmorphism, and cerebral falx calcification. More than 100 other clinical manifestations have also been described in the literature including ovarian fibroma, enlarged cerebral ventricles, and lymphatic as well as chylous mesenteric cysts. The Patched (PTCH) gene is responsible for GS when mutated. Here, we report on a prenatal diagnosis of GS in a girl with a chylothorax, a previously unreported feature in GS. We discuss the clinical features observed in this family and we comment on the molecular studies that allowed us to describe a previously unreported Patched gene mutation.


Robotic Resection of Hilar Cholangiocarcinoma.
Hilar cholangiocarcinoma is the most common malignant neoplasm of the biliary tract. Surgical resection is the only curative modality of treatment. The aim of this video is to present a robotic left hepatectomy extended to caudate lobe, combined with bile duct resection, lymphadenectomy, and Roux-en-Y biliary reconstruction. A 76-year-old female presented with progressive jaundice due to hilar cholangiocarcinoma. She underwent chemoradiation and after 5 months of treatment was referred for second opinion; imaging reevaluation showed objective response and no arterial invasion. Multidisciplinary team decided for radical treatment, which consisted in robotic left hepatectomy, caudate lobe resection, resection of bile duct, lymphadenectomy, and hepaticojejunostomy. Operative time was 8 h. Estimated blood loss was 740 mL (received 2 U). The patient's recovery was complicated by drainage clogging resulting in fever and perihepatic fluid collection, successfully treated by change of drainage. Pathology confirmed cholangiocarcinoma with free surgical margins (T1aN0). The patient is well, with no signs of disease 5 months after the procedure. Robotic resection of hilar cholangiocarcinoma is feasible and safe. The robotic approach has some technical advantages over laparoscopic approach. This video may help oncological surgeons to perform this complex procedure.


The evolution of alpha-fetoprotein and albumin. I. A comparison of the primary amino acid sequences of mammalian alpha-fetoprotein and albumin.
The amino acid sequence of mouse alpha-fetoprotein has been deduced from the nucleotide sequence of its mRNA and three chimeric plasmids containing overlapping segments of its cDNA. A comparison of the amino acid sequence with that of either human and bovine albumin reveals in each case a 32% conservation of primary sequence. In addition, using the regularly spaced positions of cystine bridges, a 2-dimensional structure was generated, which revealed the presence of 3 closely related domains within alpha-fetoprotein. The structures of these domains are identical with the triplicated domains previously observed in several mammalian albumins. These homologies lend strong circumstantial evidence to the proposal that these two proteins arose in evolution as the consequence of a duplication in a common tripartite ancestral gene.


The Fluidity of the Bacterial Outer Membrane Is Species Specific: Bacterial Lifestyles and the Emergence of a Fluid Outer Membrane.
The outer membrane (OM) is an essential barrier that guards Gram-negative bacteria from diverse environmental insults. Besides functioning as a chemical gatekeeper, the OM also contributes towards the strength and stiffness of cells and allows them to sustain mechanical stress. Largely influenced by studies of Escherichia coli, the OM is viewed as a rigid barrier where OM proteins and lipopolysaccharides display restricted mobility. Here the discussion is extended to other bacterial species, with a focus on Myxococcus xanthus. In contrast to the rigid OM paradigm, myxobacteria possess a relatively fluid OM. It is concluded that the fluidity of the OM varies across environmental species, which is likely linked to their evolution and adaptation to specific ecological niches. Importantly, a fluid OM can endow bacteria with distinct functions for cell-cell and cell-environment interactions.


[Cu(C8H16N4O2)0.5[N(CN)2]]n, a novel ladder-like coordination polymer.
A new polymeric copper complex, viz. catena-poly[[[mu-N,N'-bis(3-aminopropyl)oxamidato-kappa6N,N',O:N",N"',O']dicopper(II)]-di-mu-dicyanamido-1:1'kappa2N1:N5;2:2'kappa2N1:N5], [Cu2(C8H16N4O2)(C2N3)2]n or [Cu(oxpn)0.5[N(CN)2]]n [where H2oxpn is N,N'-bis(3-aminopropyl)oxamide], has been synthesized by the reaction of Cu(oxpn), [Cu(ClO4)2].6H2O and NaN3. In the crystal structure, the Cu atom is five-coordinate and has a square-pyrimidal (SP) configuration. In the polymer, dicyanamide (dca-) groups link CuII cations in a mu-1,5-bridging mode, generating novel ladders in which each step is composed of dimeric [Cu2(oxpn)]2+ cations. Abundant hydrogen bonds connect the polymer ladders into a two-dimensional network structure.


Characterization of Renal Injury and Inflammation in an Experimental Model of Intravascular Hemolysis.
Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology and clinical features. A frequent adverse effect related to massive hemolysis is the renal injury and inflammation. Nevertheless, it is still unclear whether heme--a danger-associated molecular pattern--and ligand for TLR4 or upstream hemolysis-derived products are responsible for these effects. Well-characterized animal models of hemolysis with kidney impairment are needed to investigate how hemolysis drives kidney injury and to test novel therapeutic strategies. Here, we characterized the pathological processes leading to acute kidney injury and inflammation during massive intravascular hemolysis, using a mouse model of phenylhydrazine (PHZ)-triggered erythrocyte destruction. We observed profound changes in mRNA levels for markers of tubular damage (Kim-1, NGAL) and regeneration (indirect marker of tubular injury, Ki-67), and tissue and vascular inflammation (IL-6, E-selectin, P-selectin, ICAM-1) in kidneys of PHZ-treated mice, associated with ultrastructural signs of tubular injury. Moreover, mass spectrometry revealed presence of markers of tubular damage in urine, including meprin-α, cytoskeletal keratins, α-1-antitrypsin, and α-1-microglobulin. Signs of renal injury and inflammation rapidly resolved and the renal function was preserved, despite major changes in metabolic parameters of PHZ-injected animals. Mechanistically, renal alterations were largely heme-independent, since injection of free heme could not reproduce them, and scavenging heme with hemopexin in PHZ-administered mice could not prevent them. Reduced overall health status of the mice suggested multiorgan involvement. We detected amylasemia and amylasuria, two markers of acute pancreatitis. We also provide detailed characterization of renal manifestations associated with acute intravascular hemolysis, which may be mediated by hemolysis-derived products upstream of heme release. This analysis provides a platform for further investigations of hemolytic diseases and associated renal injury and the evaluation of novel therapeutic strategies that target intravascular hemolysis.


Synthesis and application of novel multi-arm poly(carboxylic acid)s for glass-ionomer restoratives.
We have developed a novel glass-ionomer cement system composed of multi-arm poly(acrylic acid-co-itaconic acid)s. These polyacids were synthesized via a chain-transfer polymerization reaction using newly synthesized multi-arm chain-transfer agents. The cements formulated with the multi-arm polyacids showed significantly lower viscosities in water as compared to those formulated with the linear polyacids. Due to the lower viscosities, the MW of the polyacids can be significantly increased for enhanced mechanical strengths, while keeping the ease of mixing and handling. The experimental cements showed significantly improved compressive strengths as compared to Fuji II after aged in water for 3 months.


The effect of dream report collection and dream incorporation on memory consolidation during sleep.
Collecting dream reports typically requires waking subjects up from their sleep-a method that has been used to study the relationship between dreams and memory consolidation. However, it is unclear whether these awakenings influence sleep-associated memory consolidation processes. Furthermore, it is unclear how the incorporation of the learning task into dreams is related to memory consolidation. In this study we compared memory performance in a word-picture association learning task after a night with and without awakenings in 22 young and healthy participants. We then examined if the stimuli from the learning task are successfully incorporated into dreams, and if this incorporation is related to the task performance the next morning. We show that while the awakenings impaired both subjective and objective sleep quality, they did not affect sleep-associated memory consolidation. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. When dreams were collected in the morning, no incorporations were detected. Task incorporation into non-rapid eye movement sleep dreams, but not rapid eye movement sleep dreams positively predicted memory performance the next morning. We conclude that the method of awakenings to collect dream reports is suitable and necessary for dream and memory studies. Furthermore, our study suggests that dreams in non-rapid eye movement rather than rapid eye movement sleep might be related to processes of memory consolidation during sleep.


Binding of diphtheria toxin to phospholipids in liposomes.
Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine/cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of diphtheria toxin to cells.


Stress hysteresis as the cause of persistent holes in particulate suspensions.
Concentrated particulate suspensions under vibrations can support stable, localized, vertically oriented free surfaces. The most robust of these structures are persistent holes: deep and stable depressions of the interface. Using a reduced model of the hydrodynamics we show that a rheology with hysteresis can lead to motion opposite to the time-averaged applied force. Moreover, we show experimentally that particulate suspensions of cornstarch in water exhibits hysteresis in the shear-rate response to an applied sinusoidal stress. The results of our model and our experiments suggest that hysteresis accounts for the outward force needed to support persistent holes.


The impact of the revised electromagnetic compatibility standard.
Electromedical equipment must be tested to the electromagnetic compatibility (EMC) standard EN 60601-1-2 to carry the CE mark. The new version of EN 60601-1-2, which becomes mandatory from 1 November 2004, could affect the design of some products. This article summarises the new EMC requirements and provides design tips on how to meet them.


A review of interprofessional dissemination and education interventions for recognizing and managing dementia.
The number of individuals with dementia is expected to increase dramatically over the next 20 years. Given the complicated clinical, sociobehavioral, and caregiving skills that are needed to comprehensively assess and manage individuals with dementia, the gold standard of care requires involvement of interprofessional teams. This systematic review examined 4,023 abstracts, finding 18 articles from 16 studies where an interprofessional dissemination program was performed. Most studies found some improvement in clinician knowledge or confidence, or patient outcomes, though methods and patient and clinician populations were disparate. Although a significant evidence base for assessing and managing individuals with dementia has been developed, few studies have examined how to disseminate this research, and even fewer in an interprofessional manner. These findings suggest that greater emphasis needs to be placed on disseminating existing evidence-based care and ensuring that programs are interprofessional in nature so that excellent, patient-centered care is provided.


Kirenol upregulates nuclear annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats.
Kirenol is a diterpenoid compound purified from the Chinese Herba Siegesbeckiae. Siegesbeckiae has been employed for the treatment of arthritis for centuries, its safety and efficacy are documented through a long history of human use. To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of kirenol. Kirenol was administrated intragastrically in rats after the onset of CIA. Pathological changes were evaluated by paw swelling and histopathology. Concentration of IL-1β in synovial fluid and adrenal corticotropin (ACTH) in plasma were determined by Elisa. Western blot was performed to detect the expression of annexin-1 and glucocorticoid receptor alpha (GRα) in synovium. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assays (EMSA). Kirenol (1, 2, and 4 mg/kg) and prednisolone depressed paw swelling and reduced IL-1β of synovial fluid in the CIA rats (p<0.05 or p<0.01). Kirenol and prednisolone upregulated nuclear annexin-1 and inhibited NF-κB activity in synovium of CIA. The inhibitory effect of kirenol and prednisolone on NF-κB activity was enhanced by anti-annexin-1 Ab. Prednisolone, but not kirenol, downregulated plasma ACTH and GRα expression significantly (p<0.01). Kirenol and prednisolone can upregulate nuclear annexin-1 which interacts with NF-κB to inhibit NF-κB activity, reduce cytokines expression and thereby attenuate inflammation of CIA joints. Kirenol does not lead to ACTH or GR downregulation, which is in contrast to classic glucocorticoid prednisolone. Kirenol shares with GCs similar anti-inflammatory mechanism but bypass the considerable limitation of GCs treatment.


Burnout syndrome among nurses at a military medical academy in Serbia.
Healthcare workers are the professional group at higher risk of burnout than others. It is the underlying reason for medical errors and the general decrease in quality of patient care and is related to poor patient-healthcare worker relationships. Healthcare workers who work with military personnel have specificities compared to healthcare workers who work only with civilians. A cross-sectional study among 171 nurses at the Military Medical Academy was conducted. The questionnaire consisted of items regarding socio-demographic and socioeconomic characteristics, lifestyle characteristics, workplace environment, workplace stress, strategies of stress management, symptoms and signs of workplace-related stress, and the Serbian version of the Maslach Burnout Inventory. The prevalence of burnout was 46.2%. The multivariate logistic regression analysis showed that the burnout was associated with stating that they would not choose the same profession again (OR = 4.54, 95% CI: 1.53-14.50) and with not being interested in the work (OR = 4.86, 95% CI: 1.58-14.92). The prevalence of burnout is relatively high among nurses at the Medical Military Academy in Belgrade and is associated with factors in the work environment.


Adaptive designs with arbitrary dependence structure.
Adaptive designs were originally developed for independent and uniformly distributed p-values. There are trial settings where independence is not satisfied or where it may not be possible to check whether it is satisfied. In these cases, the test statistics and p-values of each stage may be dependent. Since the probability of a type I error for a fixed adaptive design depends on the true dependence structure between the p-values of the stages, control of the type I error rate might be endangered if the dependence structure is not taken into account adequately. In this paper, we address the problem of controlling the type I error rate in two-stage adaptive designs if any dependence structure between the test statistics of the stages is admitted (worst case scenario). For this purpose, we pursue a copula approach to adaptive designs. For two-stage adaptive designs without futility stop, we derive the probability of a type I error in the worst case, that is for the most adverse dependence structure between the p-values of the stages. Explicit analytical considerations are performed for the class of inverse normal designs. A comparison with the significance level for independent and uniformly distributed p-values is performed. For inverse normal designs without futility stop and equally weighted stages, it turns out that correcting for the worst case is too conservative as compared to a simple Bonferroni design.


[Diagnosis of community acquired pneumonia in adults].
In contrast with acute bronchitis, which is benign and very frequent, community acute pneumonia has to be considered as a serious illness with a mortality rate that can reach 10-15% in inpatients. In adult, pneumonia is usually due to bacteria and antibiotherapy is always required. Clinical diagnosis is based on presumption signs: fever, tachycardia, tachypnea, thoracic pain, localised rales and a global severity impression. A chest X-ray is required. The pathogens involved are usually Streptococcus pneumoniae or atypical organisms. In inpatients (severe pneumonia or presence of risk factors), other pathogens such as gram negative bacilli or anaerobes are possible. The accurate diagnosis is based on invasive methods, which are not justified in outpatients but indicated in severe pneumonia.


Droplet digital PCR revealed high concordance between primary tumors and lymph node metastases in multiplex screening of KRAS mutations in colorectal cancer.
The proto-oncogene KRAS belongs among the most frequently mutated genes in all types of cancer and is also very important oncogene related to colorectal tumors. The detection of mutations in this gene in primary tumor is a predictive biomarker for the anti-EGFR therapy in metastatic CRC (mCRC); however, the patients with wild-type KRAS can also show resistance to the personalized medicine. The droplet-based digital PCR technology has improved the analytical sensitivity of the mutations detection, which led us to the idea about the optimization of this approach for KRAS testing. In this study, we report the application of ddPCR technology in order to analyze the presence of KRAS mutations in primary tumor and matched metastasis in lymph nodes (LNs) from patients with mCRC and address the question, whether the improvement in the detection method can lower the discrepancies of KRAS mutations detection between the primary tumor and regional LNs. Genomic DNA with wtKRAS and commercial DNA with mtKRAS (G12D) were used to set up the ddPCR reaction. Formalin-fixed paraffin-embedded tissues from primary tumor and positive lymph node from 31 patients with mCRC were analyzed using ddPCR and Sanger sequencing. KRAS status of primary tumors was known; however, the mutation status of lymph nodes was not detected previously. From 31 samples of primary tumors, our results corresponded to results from IVD kit in 30 cases. For one patient, ddPCR detected KRAS mutation in comparison with negative result of the IVD kit. In the samples of metastatic infiltrated LNs, ddPCR detected 16 samples as a WT KRAS and 15 lymph nodes showed positivity for KRAS mutation, whereby Sanger sequencing found KRAS mutations in 8 cases only. We also found two cases where genetic conditions of KRAS gene differed between primary tumor and infiltrated lymph node, both "low-grade" adenocarcinoma. Our study approved that ddPCR method is adequate technique with high sensitivity and in the future may be used as a diagnostic tool for evaluation of KRAS mutations, especially in infiltrated LNs of patients with mCRC.


Number of histocompatibility loci in Syrian hamsters.
Syrian hamsters descended from animals captured in the summer of 1971 have been utilized to obtain some estimate of the number of histocompatibility loci in this species. The survival of skin grafts on two F2 populations derived from these animals and two isogenic stocks indicates considerably more histocompatibility loci than previously reported.


Twin pregnancy chorionicity determination in a tertiary care setting.
Ultrasound determination of chorionicity is most reliable before 14 weeks and subsequently reduces in accuracy with advancing gestation. The aim of this study was to evaluate the accuracy of chorionicity determination in a birth cohort of twin pregnancies. Antenatal ultrasound determination of chorionicity in twin pregnancy was undertaken at suboptimal period of gestation in over twothirds of twin pregnancies. Even in the first trimester of pregnancy, the accuracy of chorionicity determination was lower than previously reported.


[In vitro effects of ionic and non-ionic contrast media on erythrocyte aggregation].
An in vitro model was designed to examine the effect of three contrast media (CM): two non ionic (Iohexol, Iopamidol) and one ionic (Ioxaglate) molecules on erythrocyte aggregation. Red blood cells were suspended in a chemically defined medium (Albumin: 10 g/l), Immunoglobulins: 12 g/l, Fibrinogen: 1.5 g/l) supplemented with various proportions of CM (10-25% V/V). Control samples contained NaCl or Saccharose solutions with a nearly similar osmolality. Erythrocyte aggregation at constant hematocrit (HT = 40%) was determined by the analysis of the light backscattered by blood suspension during the aggregation process. As compared to control samples, non ionic CM induced a weak decrease in erythrocyte aggregation, when the ionic molecule caused a marked increase in the aggregation, which was related to CM concentration. A different interaction of ionic and non ionic CM with erythrocyte membranes has been shown by fluorescence studies. After addition of CM, it was noted a fluorescence quenching of lipophilic probes (TMA-DPH and DPH) embedded in erythrocyte membranes. This quenching probably due to benzene ring and iodine atoms of contrast media markedly varied according to the used fluorescent probe and the CM. In the presence of ionic CM, the fluorescence quenching is more important than that induced by non ionic CM. Thus, besides osmolality and viscosity of CM which play a role in erythrocyte aggregation, some intrinsic properties of CM such as the ionic or non ionic nature could influence erythrocyte membrane-contrast medium interactions and consequently erythrocyte aggregation.


Ethnobotany & ethnopharmacology of Tabernaemontana divaricata.
Tabernaemontana divaricata a common garden plant in tropical countries has been used as a traditional medicine. However, no recent review articles of T. divaricata, particularly discussing its pharmacological properties, are available. This review presents the ethnobotany and ethnopharmacology of T. divaricata as well as its potential therapeutic benefits especially of the alkaloidal and non-alkaloidal constituents. Included, are the characteristics of 66 alkaloids isolated and identified from T. divaricata. Non-alkaloids including the enzymes, pyrolytic oil, hydrocarbons, terpenoid and phenolic acids are also documented. Chemotaxonomic aspects of each alkaloid as well as information regarding the pharmacology of crude extracts and individual alkaloids from T. divaricata have been assembled and appraised. The beneficial properties of T. divaricata are antioxidant, anti-infection, anti-tumour action, analgesia and the enhancement of cholinergic activity in both peripheral and central nervous systems. The augmentation of cholinergic function may be of therapeutic benefit for many neurodegenerative diseases, particularly myasthenia gravis and Alzheimer's disease.


Usefulness of computed tomography with air insufflation of the stomach prior to percutaneous endoscopic gastrostomy procedure.
We examined the results of computed tomography (CT) with and without air insufflation of the stomach prior to performing percutaneous endoscopic gastrostomy (PEG). We retrospectively analyzed 366 patients who underwent PEG. CT images obtained with and without air insufflation were examined for the presence or absence of contact between the gastric anterior wall and abdominal wall. PEG outcome based on CT findings was also examined. CT with and without air insufflation was performed in 272 and 94 patients, respectively. Contact between the gastric anterior wall and abdominal wall was shown in 254 (93.4%) with and 45 (47.9%) without air insufflation, all of whom underwent a successful PEG procedure. In patients without contact between the gastric anterior wall and abdominal wall, PEG was not successful in 3 of 49 (6.1%) examined by CT without and 6 of 18 (33.3%) examined with air insufflation (p = 0.004). Values for diagnostic accuracy for contact between the gastric anterior wall and abdominal wall shown by CT with and without air insufflation in successful PEG cases were 0.96 and 0.51, respectively. In conclusion, CT with air insufflation more often revealed contact between the gastric anterior wall and abdominal wall as compared to CT without air insufflation, which may help to predict PEG procedure success.


Comprehensive Analysis of Human Cytomegalovirus- and HIV-Mediated Plasma Membrane Remodeling in Macrophages.
The plasma membrane (PM) must be overcome by viruses during entry and release. Furthermore, the PM represents the cellular communication compartment and the immune system interface. Hence, viruses have evolved sophisticated strategies to remodel the PM, for instance to avoid immune sensing and clearance of infected cells. We performed a comprehensive analysis of cell surface dysregulation by two human-pathogenic viruses, human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1), in primary macrophages, which are classical antigen-presenting cells and orchestrators of the immune system. Scanning ion conductance microscopy revealed a loss of roughness and an overall smooth phenotype of HCMV-infected macrophages, in contrast to HIV-1 infection. This phenotype was also evident on the molecular level. When we screened for cell surface receptors modulated by HCMV, 42 of 332 receptors tested were up- or downregulated, whereas HIV-1 affected only 7 receptors. In particular CD164, CD84, and CD180 were targeted by HCMV. Mechanistically, HCMV induced transcriptional silencing of these receptors in an interferon (IFN)-independent manner, and expression was reduced not only by lab-adapted HCMV but also by clinical HCMV isolates. Altogether, our plasma membrane profiling of human macrophages provides clues to understand how viruses evade the immune system and identified novel cell surface receptors targeted by HCMV. IMPORTANCE The PM is a key component that viruses have to cope with. It is a barrier for infection and egress and is critically involved in antiviral immune signaling. We hence asked the question how two immunomodulatory viruses, HIV-1 and HCMV, dysregulate this compartment in infected macrophages, relevant in vivo targets of both viruses. We employed a contact-free microscopic technique to image the PM of infected cells and performed a phenotypic flow cytometry-based screen to identify receptor modulations on a molecular level. Our results show that HIV-1 and HCMV differentially manipulate the PM of macrophages. While HIV-1-mediated changes are relatively subtle, HCMV induces major alterations of the PM. We identify novel immune receptors manipulated by HCMV and define mechanisms of how HCMV interferes with receptor expression. Altogether, our study reveals differential strategies of how two human-pathogenic viruses manipulate infected cells and identifies potential novel pathways of HCMV immune evasion.


Oligosaccharide-mediated inhibition of the adhesion of pathogenic Escherichia coli strains to human gut epithelial cells in vitro.
The aim of the study was to investigate the ability of pectic oligosaccharides (POS) to inhibit adhesion of three strains of verotoxigenic Escherichia coli, three strains of enteropathogenic E. coli, and one nonclinical strain of Desulfovibrio desulfuricans to human intestinal epithelial cell cultures. Lactobacillus acidophilus and Lactobacillus gasseri were included for comparison. Attachment was determined in the human HT29 cell line by viable count of adherent bacteria. POS in buffer at pH 7.2 were antiadhesive at a dose of 2.5 mg ml(-1), reducing adhesion of enteropathogenic E. coil and verotoxigenic E. coli strains to less than 30% of control values. Concentrations resulting in 50% inhibition ranged from 0.15 to 0.46 mg ml(-1). L. acidophilus was not significantly affected, but adhesion of L. gasseri was reduced to 29% of the control value. POS reduced the adhesion of D. desulfuricans to 0.33% of the control value. POS also had a protective effect against E. coli verocytotoxins VT1 and VT2 at concentrations of 0.01 and 1 microg ml(-1), respectively.


A Boolean view separates platelet activatory and inhibitory signalling as verified by phosphorylation monitoring including threshold behaviour and integrin modulation.
Platelets are critical for haemostasis and blood clotting. However, since under normal circumstances blood should flow without clotting, its function is regulated via a complex interplay of activating and inhibiting signal transduction pathways. Understanding this network is crucial for treatment of cardiovascular and bleeding diseases. Detailed protein interaction and phosphorylation data are explored to establish a simplified Boolean model of the central platelet cascades. We implemented the model by means of CellNetAnalyzer and showed how different signalling events coalesce into a fully activated system state. Furthermore, we examined the networks' inherent threshold behaviour using the semi-quantitative modelling software SQUAD. Finally, predictions are verified monitoring phosphorylations which mark different activation phases as modelled. The model can also be applied to simulate different pharmacological conditions as they modify node activity (aspirin, clopidogrel, milrinon, iloprost, combination) and is available for further studies. It agrees well with observations. Activatory pathways are diversified to cope with complex environmental conditions. Platelet activation needs several activation steps to integrate over different network subsets, as they are formed by the interplay of activating kinases, calcium mobilization, and the inhibiting cAMP-PKA system. System stability analysis shows two phases: a sub-threshold behaviour, characterized by integration over different activatory and inhibitory conditions, and a beyond threshold phase, represented by competition and shutting down of counter-regulatory pathways. The integrin network and Akt-protein are critical for stable effector response. Dynamic threshold-analysis reveals a dependency of the relative activating input strength necessary to irreversibly engage the system from the absolute inhibitory signal strength.


Conjugal amyotrophic lateral sclerosis: a case report from Scotland.
Conjugal amyotrophic lateral sclerosis is rare, with significant effects on psychological and care needs. We report a case of conjugal amyotrophic lateral sclerosis disease from central Scotland. This case is particularly unusual as both patients were diagnosed within an 18-month period and experienced the disease simultaneously, with similar symptomatology and progression. Patient A was a 71-year-old man who presented with unilateral arm weakness and wasting. Patient B was a 68-year-old woman who presented with unilateral shoulder and elbow weakness. Diagnosis of amyotrophic lateral sclerosis was made within a few months of presentation in both cases, based on typical clinical symptomatology together with supportive neurophysiological testing. Interventions included enteral feeding and non-invasive ventilation. The time period between symptom onset and death was 5 years for Patient A and 3.5 years for Patient B. This case illustrates two main points: the care issues surrounding cases of conjugal neurological disease, and the psychological issues in these patients. There are significant care issues arising when co-habiting couples both develop severe functionally limiting neurological diseases at the same time. The more slowly progressive nature of Patient A's disease may be at least partially explained by the support he was able to receive from Patient B before she developed symptoms. Secondly, there are important psychological effects of living with someone with the same - but more advanced - progressive and incurable neurological disease. Thus, Patient B was reluctant to have certain interventions that she had observed being given to her husband. Lastly, no plausible shared environmental risk factors were identified, implying that the co-occurrence of ALS in this couple was a random association.


Glycine betaine accumulation, ionic and water relations of red-beet at contrasting levels of sodium supply.
Exposure of plants to sodium (Na) and salinity may increase glycine betaine accumulation in tissues. To study this, red-beet cvs. Scarlet Supreme and Ruby Queen, were grown for 42 days in a growth chamber using a re-circulating nutrient film technique with 0.25 mmol/L K and either 4.75 mmol/L (control) or 54.75 mmol/L (saline) Na (as NaCl). Plants were harvested at weekly intervals and measurements were taken on leaf water relations, leaf photosynthetic rates, chlorophyll fluorescence, chlorophyll levels, glycine betaine levels, and tissue elemental composition. Glycine betaine accumulation increased under salinity and this accumulation correlated with higher tissue levels of Na in both cultivars. Na accounted for 80 to 90% of the total cation uptake under the saline treatment. At final harvest (42 days), K concentrations in laminae ranged from approximately 65-95 micromoles g-1 dry matter (DM), whereas Na in shoot tissue ranged from approximately 3000-4000 micromoles g-1. Leaf sap osmotic potential at full turgor [psi(s100)] increased as lamina Na content increased. Glycine betaine levels of leaf laminae showed a linear relationship with leaf sap [psi(s100)]. Chlorophyll levels, leaf photosynthetic rates, and chlorophyll fluorescence were not affected by Na levels. These results suggest that the metabolic tolerance to high levels of tissue Na in red-beet could be due to its ability to synthesize and regulate glycine betaine production, and to control partitioning of Na and glycine betaine between the vacuole and the cytoplasm.


Impact of failed allograft nephrectomy on initial function and graft survival after kidney retransplantation.
The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.


Identification of T-type alpha1H Ca2+ channels (Ca(v)3.2) in major pelvic ganglion neurons.
Among autonomic neurons, sympathetic neurons of the major pelvic ganglia (MPG) are unique by expressing low-voltage-activated T-type Ca2+ channels. To date, the T-type Ca2+ channels have been poorly characterized, although they are believed to be potentially important for functions of the MPG neurons. In the present study, thus we investigated characteristics and molecular identity of the T-type Ca2+ channels using patch-clamp and RT-PCR techniques. When the external solution contained 10 mM Ca2+ as a charge carrier, T-type Ca2+ currents were first activated at -50 mV and peaked around -20 mV. Besides the low-voltage activation, T-type Ca2+ currents displayed typical characteristics including transient activation/inactivation and voltage-dependent slow deactivation. Overlap of the activation and inactivation curves generated a prominent window current around resting membrane potentials. Replacement of the external Ca2+ with 10 mM Ba2+ did not affect the amplitudes of T-type Ca2+ currents. Mibefradil, a known T-type Ca2+ channel antagonist, depressed T-type Ca2+ currents in a concentration-dependent manner (IC50 = 3 microM). Application of Ni2+ also produced a concentration-dependent blockade of T-type Ca2+ currents with an IC50 of 10 microM. The high sensitivity to Ni2+ implicates alpha1H in generating the T-type Ca2+ currents in MPG neurons. RT-PCR experiments showed that MPG neurons predominantly express mRNAs encoding splicing variants of alpha1H (called pelvic Ta and Tb, short and long forms of alpha1H, respectively). Finally, we tested whether the low-threshold spikes could be generated in sympathetic MPG neurons expressing T-type Ca2+ channels. When hyperpolarizing currents were injected under a current-clamp mode, sympathetic neurons produced postanodal rebound spikes, while parasympathetic neurons were silent. The number of the rebound spikes was reduced by 10 microM Ni2+ that blocked 50% of T-type Ca2+ currents and had a little effect on HVA Ca2+ currents in sympathetic MPG neurons. Furthermore, generation of the rebound spikes was completely prevented by 100 microM Ni2+ that blocked most of the T-type Ca2+ currents. In conclusions, T-type Ca2+ currents in MPG neurons mainly arise from alpha1H among the three isoforms (alpha1G, alpha1H, and alpha1I) and may contribute to generation of low-threshold spikes in sympathetic MPG neurons.


Characterizing the Performance of Pipe Bombs.
Pipe bombs of steel or PVC fragment in reproducible patterns when similarly configured. The power of the explosion correlates with number, mass, and size of the fragments recovered, where a large number of small, low-mass fragments indicate a high-power event and vice versa. In discussing performance, describing pipe fragmentation pattern by fragment weight distribution mapping (FWDM) or fragment surface area distribution mapping (FSADM) was useful. When fillers detonated, detonation velocities of ~4.4 mm/μs were measured. In such cases, side walls of the pipe were thrown first; the average fragment velocity was ~1000 km/s. In deflagrations, the end cap was first thrown; fragment velocities were only ~240 km/s. Blast overpressures varied; at 10 feet, 2 × 12 inch steel pipes containing ~550 g of detonable mixture produced overpressures of 5-6 psi; similar nondetonating pipes produced less than 2 psi. Maximum fragment throw distances were 250-300 m, with an average of ~100 m.


Origin of hexavalent chromium in groundwater: The example of Sarigkiol Basin, Northern Greece.
Hexavalent chromium constitutes a serious deterioration factor for the groundwater quality of several regions around the world. High concentrations of this contaminant have been also reported in the groundwater of the Sarigkiol hydrological basin (near Kozani city, NW Greece). Specific interest was paid to this particular study area due to the co-existence here of two important factors both expected to contribute to Cr(VI) presence and groundwater pollution; namely the area's exposed ophiolitic rocks and its substantial fly ash deposits originating from the local lignite burning power plant. Accordingly, detailed geochemical, mineralogical, hydro-chemical, geophysical and hydrogeological studies were performed on the rocks, soils, sediments and water resources of this basin. Cr(VI) concentrations varied in the different aquifers, with the highest concentration (up to 120μgL-1) recorded in the groundwater of the unconfined porous aquifer situated near the temporary fly ash disposal site. Recharge of the porous aquifer is related mainly to precipitation infiltration and occasional surface run-off. Nevertheless, a hydraulic connection between the porous and neighboring karst aquifers could not be delineated. Therefore, the presence of Cr(VI) in the groundwater of this area is thought to originate from both the ophiolitic rock weathering products in the soils, and the local leaching of Cr(VI) from the diffused fly ash located in the area surrounding the lignite power plant. This conclusion was corroborated by factor analysis, and the strongly positively fractionated Cr isotopes (δ53Cr up to 0.83‰) recorded in groundwater, an ash leachate, and the bulk fly ash. An anthropogenic source of Cr(VI) that possibly influences groundwater quality is especially apparent in the eastern part of the Sarigkiol basin.


B cell adaptor for PI3-kinase (BCAP) modulates CD8+ effector and memory T cell differentiation.
CD8+ T cells respond to signals via the T cell receptor (TCR), costimulatory molecules, and immunoregulatory cytokines by developing into diverse populations of effector and memory cells. The relative strength of phosphoinositide 3-kinase (PI3K) signaling early in the T cell response can dramatically influence downstream effector and memory T cell differentiation. We show that initial PI3K signaling during T cell activation results in up-regulation of the signaling scaffold B cell adaptor for PI3K (BCAP), which further potentiates PI3K signaling and promotes the accumulation of CD8+ T cells with a terminally differentiated effector phenotype. Accordingly, BCAP-deficient CD8+ T cells have attenuated clonal expansion and altered effector and memory T cell development following infection with Listeria monocytogenes Thus, induction of BCAP serves as a positive feedback circuit to enhance PI3K signaling in activated CD8+ T cells, thereby acting as a molecular checkpoint regulating effector and memory T cell development.


Effect of a dietary and exercise intervention in women with overweight and obesity undergoing fertility treatments: protocol for a randomized controlled trial.
Distinct molecular, inflammatory, and metabolic signatures are present in oocytes and follicular fluid derived from women with obesity when compared to those derived from normal weight women, which suggest existing signals that may program future offspring for metabolic diseases. This study aims to assess the feasibility and efficacy of a peri-conception nutrition and exercise intervention on mitigating obesity-associated changes in oocyte gene expression profiles and follicular fluid metabolites. This single blinded randomized control trial will include 120 women with a BMI of 25-45 kg/m2, ≥21 years of age, and undergoing in vitro fertilization (IVF) treatments. Participants will be randomized to standard of care (N = 60) or an intervention group (N = 60) in a block design by polycystic ovary syndrome status. The intervention will combine a dietary component (Mediterranean meal plan) with exercise prescription following the Physical Activity Guidelines for Americans. Participants will be assessed pre- and post-intervention. The standard of care group will be offered to join the intervention group if the IVF treatments are unsuccessful as a cross over design. Recruitment is anticipated to start in July of 2021. Primary outcomes will include single oocyte gene expression profiles and follicular fluid metabolites. Mann-Whitney U nonparametric tests will be used to assess potential differences for each stratum. Follicular fluid and serum metabolites will be analyzed using a one-factor Analysis of Covariance (ANCOVA) at four levels, pair-wise comparisons using Tukey-Kramer post-hoc tests will be used to identify groups whose means differ significantly while retaining the family-wise error rate at 5%. When the design is balanced, two-way Analysis of Variance (ANOVA), or non-parametric Friedman test will be used in data analysis. Additionally, general linear models and ANCOVA may be used to control for covariates. Significance will be set at p < 0.05. Findings will be disseminated via peer-reviewed manuscripts and presentations at scientific conferences. This study will provide novel data and key information on the impact of a dietary and exercise intervention on oocyte gene expression and follicular fluid content. Results will demonstrate the potential of such intervention in mitigating obesity-induced changes in oocyte gene expression and follicular fluid metabolites. ClinicalTrials.gov ( NCT04273048 ): submitted November 13, 2019; posted February 17, 2020.


Determining Roles of Potassium-Feldspar Surface Characters in Affecting Ice Nucleation.
The roles of surface characteristics of the feldspar surface on ice nucleation have remained elusive. Here, simple strategies are reported to quantitatively analyze the effects of the surface morphology and molecular composition of the potassium-feldspar surface on ice nucleation. The steps are found to be responsible to the high ice nucleation efficacy according to the fact that water drop freezing temperature increases by about 4.5 °C atop the freshly cleavage feldspar surface being rich of steps comparing to the flattened ones. After the molecular component and atomic structure are destroyed by the fluorination, a tremendous decrease of the ice nucleation temperatures by around 9.0 °C is observed on both cleavage and flattened surfaces, and the steps still improve the ice nucleation activity of the hydrophobic cleavage surfaces. The influence of the surface composition also implies the importance of the molecular component and structure specificity on K-feldspar in facilitating ice nucleation.


Construction and Validation of a Ferroptosis-Related Prognostic Model for Gastric Cancer.
Gastric cancer (GC), an extremely aggressive tumor with a very different prognosis, is the third leading cause of cancer-related mortality. We aimed to construct a ferroptosis-related prognostic model that can be distinguished prognostically. The gene expression and the clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). The ferroptosis-related genes were obtained from the FerrDb. Using the "limma" R package and univariate Cox analysis, ferroptosis-related genes with differential expression and prognostic value were identified in the TCGA cohort. Last absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink ferroptosis-related predictors and construct a prognostic model. Functional enrichment, ESTIMATE algorithm, and single-sample gene set enrichment analysis (ssGSEA) were applied for exploring the potential mechanism. GC patients from the GEO cohort were used for validation. An 8-gene prognostic model was constructed and stratified GC patients from TCGA and meta-GEO cohort into high-risk groups or low-risk groups. GC patients in high-risk groups have significantly poorer OS compared with those in low-risk groups. The risk score was identified as an independent predictor for OS. Functional analysis revealed that the risk score was mainly associated with the biological function of extracellular matrix (ECM) organization and tumor immunity. In conclusion, the ferroptosis-related model can be utilized for the clinical prognostic prediction in GC.


A Novel Double Side Branch Protection Technique for a Left Main Trifurcation Lesion: Simultaneous Jailed Balloon and Jailed Corsair Technique.
Percutaneous coronary intervention for left main trifurcation disease is challenging. Although side branch protection techniques such as the jailed balloon technique and jailed Corsair technique are the established methods for treatment of coronary bifurcation lesions, little is known regarding the application and feasibility of these techniques for left main trifurcation disease. We herein describe a 72-year-old man with angina pectoris who was successfully treated with percutaneous coronary stent implantation for a left main trifurcation lesion. In this case, we performed a novel double side branch protection technique, the simultaneous jailed balloon and jailed Corsair technique, with a single 8 Fr guiding catheter. This is the first case report to highlight the feasibility and efficacy of combined use of the jailed balloon and jailed Corsair techniques during percutaneous coronary intervention for left main trifurcation disease.


[Efficacy and safety of monotherapy versus combination therapy in treatment of allergic rhinitis : a Meta-analysis].
Objective:To evaluate efficacy and safety of monotherapy versus combination therapy on allergic rhinitis(AR) in order to provide evidencebased reference for clinic drug treatment of AR.Method:The randomized controlled trials(RCT) about drug treatment of AR were searched in PubMed, Embase, Cochrane library, CNKI, WanFang Data. After screening the literatures, extracting the data and evaluating the quality, to compare total nasal symptom scores(TNSS),composite symptom scores(CSS),daytime nasal symptom scores(DNSS),individual nasal symptom scores, total ocular symptom scores(TOSS), daytime eye symptom scores(DESS)and incidence of adverse events(AE)between monotherapy group and combination therapy group. Meta-analysis was performed by RevMan 5.3 software.Result:A total of 12 RCTs were enrolled, 7 675 AR patients involved. The results of Metaanalysis showed that the efficacy of combination therapy group was superior to the monotherapy group in TNSS with significant difference(WMD=0.74,95%CI 0.31-1.17,P<0.05;WMD=1.40,95%CI0.98-1.82,P<0.05).Compared with monotherapy group, individual nasal symptom scores in combination group were significantly decreased. There were no significant difference in incidence of AE(headache, dysgeusia, epistaxis) between two groups(RR=1.20,95%CI 0.87-1.65, P=0.28;RR=0.63,95%CI 0.31-1.24,P=0.18;RR=0.96,95%CI 0.63-1.64, P=0.85.Conclusion:Combination therapy can remarkably improve nasal symptom in AR patients compared with monotherapy, moreover, the incidence of AE between two groups were similar. We recommend combination therapy for allergic rhinitis.


The Long-Term Change of Arrhythmias after Transcatheter Closure of Perimembranous Ventricular Septal Defects.
To observe and analyze the long-term change of different types of arrhythmias after transcatheter closure of perimembranous ventricular septal defect (pmVSD). We retrospectively collected the data of patients who underwent pmVSD closure in our institution from March 2002 to December 2010. One hundred thirty-nine patients met the inclusion criteria, of which 265 (25.5%) had early arrhythmia. They were classified into two categories: conduction abnormality (191/1039; 18.4%) and origin abnormality (94/1039; 9.0%), including 20 patients with both types of arrhythmias. The median follow-up time was 84.5 months, and 103 patients (103/191; 53.9%) with early conduction block got permanent arrhythmias, while only three patients (3/94; 3.2%) with early anomalous origin arrhythmias still had an abnormal electrocardiogram. Serious arrhythmias (28/1039; 2.7%), including II° atrioventricular block (AVB), III° AVB, and complete left bundle branch block (CLBBB), can appear immediately in the early postoperative period (21 patients) or in the late outset (seven patients) after several months or even years (6 months to 8.3 years). Twenty patients (20/21; 95.2%) with serious arrhythmia in the early postoperative period improved after early treatment, but six patients relapsed or worsened during follow-up. At the endpoint, severe arrhythmia persisted in 13 patients, of which four patients got permanent pacemaker implanted, and one patient with recurrent CLBBB died from heart failure. The probability of delayed CAVB or bundle branch block after VSD closure is low but often occurs several years after surgery. Therefore, long-term ECG follow-up should last for several years or even decades. Serious arrhythmias that appear early after transcatheter pmVSD closure may impose a risk of recurrence although they have been cured already. Close attention should be paid to the changes of cardiac function in patients with CLBBB after VSD closure, and the severity of such arrhythmia should be taken seriously and reexamined.


Chylothorax due to tuberculosis lymphadenitis.
Chylothorax is a rare clinical condition characterized by high triglyceride and low cholesterol levels in milky pleural aspirate. Generally, it occurs through leakage of chyle as result of trauma or malignancy. Chylothorax due to tuberculous lymphadenitis is very rare clinical condition that has only been documented in a few cases. Although precise pathogenesis is not known, enlarged mediastinal and hilar lymph nodes are thought to be associated with opening of collateral anastomosis between thoracic duct and the azygos and intercostal veins by creating pressure on thoracic duct and cisterna chyli. Presently described is case of chylothorax thought to be due to compression from mediastinal tuberculous lymphadenitis, and which had complete remission after antituberculosis treatment.


Chaplaincy in a Free-Standing Psychiatric Hospital During the COVID-19 Pandemic.
This Special Issue discusses the results of the international COVID-19 survey that took place during the first wave of the pandemic. This contribution discusses chaplaincy in a psychiatric hospital during the COVID-19 pandemic. Chaplaincy vignettes with patients and interventions with staff are described, showing how chaplaincy changed and remained the same during this time. The focus here is on acknowledging disturbed and broken connections, as well as intervening to sustain community.


Analysis of the psychosocial impact of caretaking on the parents of an infant with severe congenital heart defect.
This case report considers the psychosocial burden of caring for an infant with a severe congenital heart defect (CHD) on parents. Improved prenatal diagnostics and postnatal surgical intervention have created a new and increasing demographic of children and adults with CHDs that require lifelong medical care. For this reason, primary caregivers spend excessive amounts of time in hospitals and medical facilities, and must regularly decipher vast amounts of unfamiliar medical terminology and concepts with varying levels of assistance from medical personnel. This often leads to marked psychological morbidities in parental caregivers, such as stress, anxiety and depression. The financial cost of caring for infants with CHD, including loss of employment opportunities, is another important factor that impacts the quality of life of caregivers. Frequent and extended travel to seek specialised medical care, often at distant medical centres, represents an additional burden.


Amyloidosis of the breast.
We report on three cases of amyloidosis of the breast, two of which coincided with breast cancer. Patient no. 1, a 60-year-old woman, presented with two mass lesions measuring 2 cm in diameter, one in each breast. Histologically, a tubulo-lobular carcinoma was found in the left breast accompanied by vascular, interstitial, and periductal amyloid deposits; the lesion in the right breast consisted of amyloid deposits only. Patient no. 2, an 86-year-old woman, presented with an ulcerated breast tumor measuring 5 cm in diameter on the left side. A poorly differentiated invasive ductal carcinoma was found in the mastectomy specimen, and it coincided with interstitial and vascular amyloid deposits. In both patients, tumor cells had invaded the amyloid deposits. Patient no. 3, a 73-year-old woman, presented with a mass measuring 5 x 3 x 3 cm in her left breast. Fibrocystic changes, as well as interstitial and periductal amyloid deposits, were found histologically. In each case electron microscopy showed rigid, non-branching fibrils of indefinite length and measuring 10-12 nm in diameter; these were consistent with amyloid fibrils. Clinical data, immunohistochemistry, and/or amino acid sequencing of the fibril proteins extracted from formalin-fixed and paraffin-embedded tissue specimens provided evidence that the amyloid deposits were of immunoglobulin light chain origin in all three cases. A review of the literature revealed that kappa-light chain has been described more frequently than lambda-light chain in the breast and that there are no specific clinical or radiological symptoms of amyloidosis affecting the breast; a diagnosis can be achieved only by histology.


HL-A antigens in serum from bone marrow harvested for diagnostic purposes.
Tissue typing employing the lymphocytotoxicity micro-assay was performed by introducing in the system approximately 15% of autologous or homologous ultra-centrifuged blood serum, both of peripheral and bone marrow source. As a rule, the pattern of reactivity was unaffected by peripheral blood serum, whereas the cytotoxicity was nearly always inhibited by autologous bone marrow blood serum or by homologous one from donors sharing the inhibited HL-A specificities with the donors of lymphocytes. These results suggest that at least in these patients HL-A antigens are present in bone marrow blood serum at a concentration which is definitely higher than in peripheral blood.


The effect of selection history on extinction risk during severe environmental change.
Environments rarely remain the same over time, and populations are therefore frequently at risk of going extinct when changes are significant enough to reduce fitness. Although many studies have investigated what attributes of the new environments and of the populations experiencing these changes will affect their probability of going extinct, limited work has been directed towards determining the role of population history on the probability of going extinct during severe environmental change. Here, we compare the extinction risk of populations with a history of selection in a benign environment, to populations with a history of selection in one or two stressful environments. We exposed spores and lines of the green alga Chlamydomonas reinhardtii from these three different histories to a range of severe environmental changes. We found that the extinction risk was higher for populations with a history of selection in stressful environments compared to populations with a history of selection in a benign environment. This effect was not due to differences in initial population sizes. Finally, the rates of extinction were highly repeatable within histories, indicating strong historical contingency of extinction risk. Hence, information on the selection history of a population can be used to predict their probability of going extinct during environmental change.


Lumbar plexus block for the management of acute pain.
Traditional methods of managing acute pain have expanded to include PCA and epidural analgesia. The lumbar plexus block can be added to these methods. It is useful for patients undergoing some knee surgeries, both preoperatively and postoperatively. The lumbar plexus innervates both motor and sensory components of much of the anterior and medial aspects of the lower extremities. Used alone or in conjunction with NSAIDs or narcotics, lumbar plexus block avoids the lethargy and altered mental status often associated with effective doses of narcotics. Bupivacaine (Marcaine) is often the anesthetic of choice. This article describes the effective block area, catheter placement, medication administration, and specific nursing care considerations. Evaluation for medication side effects and potential toxicity are included. Potential for future use is explored.


The Effect of 2 Different Exercise Programs on Pain Intensity and Muscle Dimensions in Patients With Chronic Low Back Pain: A Randomized Controlled Trial.
The purpose of this study was to compare the effect of 2 exercise programs combined with electrotherapy on pain intensity and lumbar stabilizer muscles dimensions in patients with nonspecific chronic low back pain. A randomized controlled clinical trial was performed with 41 patients with chronic LBP. Participants were randomly allocated into 2 groups: an experimental group (n = 20) received stabilization exercises plus electrotherapy, and a control group (n = 21) received routine exercises plus electrotherapy. Pain intensity, using a visual analog scale, and muscle dimensions of both right and left transverse abdominis and lumbar multifidus muscles, using rehabilitative ultrasonography, were assessed before and immediately after 4 weeks of intervention. Significant improvement was identified after interventions on pain intensity and muscle size measurements in both groups (P < .01 in all instances). The only exception was the right-side lumbar multifidus cross-sectional area of the control group, which was not statistically significant (P = .081). No significant differences were found between the 2 exercise groups on pain intensity and muscle dimensions (P > .05 in all instances). The results of this study suggest that a combination of electrotherapy with either routine or stabilization exercise programs may improve pain intensity and muscle dimensions in patients with nonspecific chronic low back pain.


The H(3) (+) rovibrational spectrum revisited with a global electronic potential energy surface.
In this paper, we have computed the rovibrational spectrum of the H(3) (+) molecule using a new global potential energy surface, invariant under all permutations of the nuclei, that includes the long range electrostatic interactions analytically. The energy levels are obtained by a variational calculation using hyperspherical coordinates. From the comparison with available experimental results for low lying levels, we conclude that our accuracy is of the order of 0.1 cm(-1) for states localized in the vicinity of equilateral triangular configurations of the nuclei, and changes to the order of 1 cm(-1) when the system is distorted away from equilateral configurations. Full rovibrational spectra up to the H(+)+H(2) dissociation energy limit have been computed. The statistical properties of this spectrum (nearest neighbor distribution and spectral rigidity) show the quantum signature of classical chaos and are consistent with random matrix theory. On the other hand, the correlation function, even when convoluted with a smoothing function, exhibits oscillations which are not described by random matrix theory. We discuss a possible similarity between these oscillations and the ones observed experimentally.


Small bowel fistula and its impact: incorrect placement of left ventricular assist device cannulas leads to severe intestinal complications.
A young man presented with a chronic abdominal dermal irritation 4 years after implantation of a left ventricular assist device (LVAD; Berlin heart excor). The LVAD was needed because of end-stage heart failure following a chronic parvovirus B19 Infection. The implantation of mechanical circulatory support systems (MCS) has nowadays become an accepted treatment modality for patients with end-stage heart failure. Recent literature shows several intestinal complications related to MCS, but no case presents the development of a small bowel fistula to the jejunum, transversal colon and stomach. We present a case of inaccurate placement of Berlin heart excor LVAD cannulas and its impact. This case emphasises the importance of correct placement of VAD cannulas to achieve an optimal long-term result. After surgical treatment the postoperative course was prolonged because of increasing peritonitis probably based on ongoing intraperitoneal chronic contamination with intestinal germs. The patient unfortunately deceased.


Perceived Changes in Social Relations after Earthquake Trauma among Eastern Anatolian Women: Associated Factors and Mental Health Consequences.
In this study, we examined social relations in women exposed to earthquake trauma in Eastern Anatolia, Turkey. We examined women's perceptions regarding the changes in their social relations within their neighbourhood, within their marriage and with their children; analysed the factors that were associated with these relations; and tested the hypothesis that an improvement in social relations will protect women's mental health from the negative impact of earthquake trauma. Participants consisted of a random selection of 1253 women, who were interviewed regarding their psychosocial needs and mental health status 1 year after earthquake. They reported trauma-related changes in their social relations; their mental health was evaluated using the Post Traumatic Stress Diagnostic Scale and Brief Symptom Inventory. Our study demonstrated severe earthquake trauma was associated with deteriorated social relations, especially neighbourhood and marital relations. Deteriorated marital and child relations were associated with increased levels of psychiatric distress; deteriorated neighbourhood relations were associated with intrusive posttraumatic stress symptoms. Improved neighbourhood relations, but not family relations, were able to protect women's mental health from the negative impact of trauma. The results are discussed regarding their relevance to gender effects and the provision of relation-specific and symptom-specific disaster relief. Copyright © 2014 John Wiley & Sons, Ltd.


In vivo specificity of Ure2 protection from heavy metal ion and oxidative cellular damage in Saccharomyces cerevisiae.
The S. cerevisiae Ure2 protein is a prion precursor able to form large homopolymers with the characteristics of amyloid particles, a function largely restricted to its 90 N-terminal amino acids. The remaining C-terminal domain of Ure2 plays two important roles in cellular metabolism. First, it regulates nitrogen catabolic gene expression by forming a complex with the GATA transcription factor Gln3. This complex formation correlates with Gln3 being sequestered in the cytoplasm under conditions of excess nitrogen, where Gln3/Gat1-mediated transcription is minimal. Second, Ure2, which possesses structural homology with glutathione S-transferases and binds to xenobiotics and glutathione, has been recently shown to be required for Cd(II) and hydrogen peroxide detoxification. Present experiments demonstrate that Ure2 possesses a far broader protection specificity, being required to avoid the toxic effects of As(III), As(V), Cr(III), Cr(VI), Se(IV), as well as Cd(II) and Ni(II), and to varying lesser degrees Co(II), Cu(II), Fe(II), Ag(I), Hg(II), cumene and t-butyl hydroperoxides. In contrast, deletion of URE2 greatly enhances a cell's ability to withstand toxic concentrations of Zn(II) and Mo(VI). In the case of Cd(II), Ure2 does not function to decrease intracellular Cd(II) levels or influence glutathione availability for glutathionation. In fact, ure2 hypersensitivity to Cd(II) remains the same, even when glutathione is used as sole source of nitrogen for cell growth. These data suggest that Ure2 possesses a central role in metal ion detoxification, a role not demonstrably shared by either of the two known S. cerevisiae glutathione S-transferases, Gtt1 and Gtt2, or the two glutaredoxins, Grx1 and Grx2, that also possess glutathione S-transferase activity.


Construction of human monoclonal single-chain Fv antibodies against small-cell lung cancer by phage display libraries derived from cell-immunized SCID mice engrafted with human peripheral blood lymphocytes.
In this study, we describe a phage display strategy to obtain human monoclonal single-chain Fv (scFv) antibodies binding target cancer cell surface proteins. By developing a cancer cell immunization protocol for SCID mice engrafted with human peripheral blood lymphocytes in combination with an antibody phage display method, we have isolated phage antibodies binding small-cell lung cancer cell line H889 by subtractive selection. One of the isolated scFv antibodies, 12EAb, recognized the E2 component of pyruvate dehydrogenase complex (PDC-E2) by immunoprecipitation according to MALDI-TOF MS analysis. Furthermore, we have confirmed the plasma membrane localization of PDC-E2 in small-cell lung cancer cells by immunocytochemistry and cell surface protein biotinylation, although PDC-E2 is usually located in the mitochondrial matrix. These results, including unique localization of identified antigens, were obtained by proteomic approaches. The present methods can be applied to generate human monoclonal scFv antibodies against tumor cells and to identify new molecular targets for immunotherapy and markers for diagnosis.


Speech discrimination is impaired in parkinsonian patients: Expanding the audiologic findings of Parkinson's disease.
Hearing impairment (HI) has been previously demonstrated in patients with Parkinson's disease (PD). Pure Tone Audiometry (PTA) gives no information about patients' ability to hear and understand speech. To find out hearing ability and speech discrimination of PD patients, we expanded audiological evaluation by means of speech audiometry (SA). We screened a series of consecutive PD patients. Severity of motor symptoms and staging were measured by the UPDRS-III and the H&Y scales. Audiometric evaluation consisted of a standardized audiological examination, PTA and SA. Healthy age- and sex-matched subjects were selected as controls. 45 PD patients and 45 healthy controls were enrolled. PTA confirmed our previous finding of high-frequency HI in PD patients. The mean values for the Speech Recognition Threshold were higher in PD patients as compared with controls. PD patients were more likely to have impaired speech discrimination profiles and higher disease stages. Neither the patients nor the controls showed a significant speech-tone dissociation and rollover phenomenon. Our results confirmed sensorineural HI in PD patients. Moreover, SA showed impaired speech discrimination abilities in PD patients as compared with control group thus expanding the audiologic findings of PD.


Head and neck manifestations of Wegener's granulomatosis.
Wegener's granulomatosis is an idiopathic, granulomatous disease with the potential for multiple head and neck manifestations. The otolarygologist is an essential part of the multidisciplinary team involved in establishing the diagnosis and providing ongoing care for patients with Wegener's granulomatosis. Diagnostic difficulties abound in Wegener's granulomatosis, making repeat biopsies and the use of ANCA imperative. Medical therapy consisting of corticosteroids and immunosuppressive agents is the mainstay of treatment in Wegener's granulomatosis, whereas surgery is reserved for selected head and neck manifestations. With appropriate medical and surgical treatment, many patients living with Wegener's granulomatosis can enjoy a good quality of life.


Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K³]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1.
Temporins are anti-microbial peptides synthesized in the skin of frogs of the Ranidae family. The few studies to date that have examined their anti-viral properties have shown that they have potential as anti-viral therapies. In this work, we evaluated the anti-herpes simplex virus type 1 (HSV-1) activity of the temporin-SHa (SHa) and its synthetic analog [K³]SHa. Human cathelicidin LL-37 and temporin-Tb (Tb), previously demonstrated to have anti-HSV-1 properties, were used as positive controls. We observed that SHa and [K³]SHa significantly inhibit HSV-1 replication in human primary keratinocytes when used at micromolar concentrations. This anti-viral activity was equivalent to that of Tb, but lower than that of LL-37. Transcriptomic analyses revealed that SHa did not act through the modulation of the cell innate immune response, but rather, displayed virucidal properties by reducing infectious titer of HSV-1 in suspension. In contrast, pre-incubation of the virus with LL-37 suggests that this peptide does not act directly on the viral particle at non-cytotoxic concentrations tested. The anti-HSV-1 activity of LL-37 appears to be due to the potentiation of cellular anti-viral defenses through the induction of interferon stimulated gene expression in infected primary keratinocytes. This study demonstrated that SHa and [K³]SHa, in addition to their previously reported antibacterial and antiparasitic activities, are direct-acting anti-HSV-1 peptides. Importantly, this study extends the little studied anti-viral attributes of frog temporins and offers perspectives for the development of new anti-HSV-1 therapies.


Epidemiology and microbiological features of anaerobic bacteremia in two French University hospitals.
Bacteremia implicating anaerobic bacteria (BIAB) represents 2-6% of all episodes of bacteremia and is associated with high mortality. In this retrospective study from June 2015 to December 2016, we compared BIAB frequency in two hospital centers in Montpellier (France): Montpellier university hospital (MUH) and a center specialized in cancer (ICM). Among the 2465 microbiologically relevant episodes of bacteremia, we identified 144 (5.8%) in which anaerobic bacteria were implicated. BIAB frequency was higher at ICM than MUH (10.4%, vs. 4.9%, p < 0.01). Poly-microbial bacteremia was more frequent among the BIAB episodes (31.9% vs. 11.0% for aerobic-only bacteremia, p < 0.01). Bacteroides and Clostridium were the most frequently identified genera of anaerobic bacteria (64 and 18 episodes, respectively), with the B. fragilis group (BFG) involved in 68/144 episodes. We could perform antibiotic susceptibility typing in 106 of the 144 anaerobic isolates, including 67 BFG isolates. All isolates but one were susceptible to metronidazole. In the BFG, sporadic resistant or intermediate results were found for amoxicillin-clavulanate (5/67), piperacillin-tazobactam (2/67) and imipenem (1/67). BFG isolates were susceptible also to cefoxitin (90.8%), rifampicin (97.0%) and tigecyclin (91.0%). Multidrug resistance in this group (7 isolates) was mostly due to acquired resistance to moxifloxacin, clindamycin and tigecyclin. This study shows that BIAB frequency can vary among hospitals and services. They should especially be taken into account in centers specialized in cancer treatment. However, the implicated bacteria remain frequently susceptible to the most used antibiotics used against anaerobic bacteria, although resistance does exist.


Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1.
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.


Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels.
The epidermal growth factor receptor and its various ligands (epidermal growth factor, transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, heregulin, and betacellulin) have been implicated in growth and regeneration of intestinal mucosa and might be related to the development and progression of gastrointestinal tumors. Although some studies have investigated levels of epidermal growth factor receptor by radioligand binding studies, none of them have further analyzed these levels in patients with rectal cancer and investigated their prognostic value. We quantitatively determined tumor epidermal growth factor receptor levels in 38 patients with colorectal cancer compared with adjacent normal mucosa by iodine-125-labeled epidermal growth factor binding studies and Scatchard analysis. Patients were followed up for 49.5 +/- 32.2 (range, 2-120) months. Epidermal growth factor receptor capacity was increased in invasive colorectal carcinomas according to T classification (P < 0.001), tumors with lymph node infiltration (P = 0.038), and advanced International Union Against Cancer stage (P < 0.001). Survival of colorectal cancer was reduced in patients with advanced International Union Against Cancer stage (P < 0.001), tumors with positive lymph nodes (P < 0.001), and tumors with elevated epidermal growth factor receptor levels (P = 0.024). In rectal cancer patients, poor prognosis was associated with advanced International Union Against Cancer stage (P = 0.029), tumors with lymph node infiltration (P = 0.040), and increased epidermal growth factor receptor levels (P = 0.002). Multivariate Cox regression analysis indicated that elevated levels of epidermal growth factor receptor were an independent predictor of reduced survival in patients with rectal cancer (P = 0.005). The epidermal growth factor receptor/ligand system appears to be involved in tumor development and tumor progression of colorectal carcinomas, with prognostic implication especially in patients with invasive rectal carcinomas. These patients might take advantage of therapies that specifically block epidermal growth factor receptor-mediated signal transduction.


Localization of Late Gadolinium Enhancement and Its Association with Ventricular Tachycardia in Patients with Cardiac Sarcoidosis.
Sustained ventricular tachycardia (sVT), leading to sudden cardiac death, is one of the common manifestations in cardiac sarcoidosis (CS). Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been reported to be associated with sVT, the relationships of its localization to sVT have not been fully evaluated.To evaluate the localization of LGE and its relationships to sVT in patients with CS, we reviewed medical record of consecutive 31 patients with CS who underwent CMR. The localization of LGE was divided into four categories: Left ventricular (LV) septum, LV free wall, right ventricular (RV) septum, and RV free wall. We investigated the association of sVT with localization of LGE and other parameters including serum biomarkers LV ejection fraction on echocardiography and Fluorine-18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET) -CT.Of the studied population, 8 patients (25.8%) were known to present with sVT among 31 CS patients. LGE was observed in the RV free wall in 6 patients with sVT, whereas it was in 5 patients without sVT (75.0% versus 21.7%, P = 0.022). Univariate analysis showed that only LGE in the RV free wall was associated with sVT (odds ratio [OR]: 10.80; 95% confidence interval [CI]: 1.64-70.93, P = 0.013).LGE in the RV free wall was associated with sVT in patients with CS.


MAGEA6 positively regulates MSMO1 and promotes the migration and invasion of oesophageal cancer cells.
The melanoma antigen gene family A (MAGEA) family of proteins comprises of cancer-testis antigens that are highly expressed in a number of tumours but are minimally expressed in normal cells. Due to its expression characteristics, this protein family has become a popular target for anti-cancer drugs and immunotherapy research over recent years. Although, elevated expression levels of MAGEA6 has been found in different types of tumours, there remains to be insufficient information on the function of MAGEA6 and its associated gene regulation pathways. The present study used Transwell, Cell Counting Kit-8 and wound healing assays to analyse the effects of MAGEA6 on Eca109 cell invasion, migration and proliferation. The main functions and pathways involved in MAGEA6 were predicted by Illumina Hiseq screening for mutually regulated genes and core genes. Eca109 cell line with a high expression of MAGEA6 was a stable cell line obtained by transfection in the early stage, and this cell line was used in subsequent experiments. Transcriptome sequencing was performed on this cell line and the Eca109 cell line that normally expressed MAGEA6. It was revealed that a high expression of MAGEA6 conferred a significant stimulating effect on cell proliferation whilst also significantly increasing cell invasion and migration. Transcriptomic analysis identified 14 differentially expressed genes and 13 core regulatory genes closely associated with MAGEA6 expression regulation, such as methylsterol monooxygenase 1 (MSMO1). The present study suggest that MAGEA6 positively regulated MSMO1 expression, which may serve an oncogenic role in cells through this regulatory effect. Overall, this provided a novel route of investigation for an in-depth study of the regulatory function of MAGEA6.


[Analysis of TGFBI gene mutation in a Chinese pedigree affected with lattice corneal dystrophy].
To explore the clinical features and mutation of TGFBI gene in a Chinese pedigree affected with lattice corneal dystrophy (LCD). Genomic DNA was extracted from 35 members including 11 patients from the pedigree. The 17 exons and splicing region of introns of the TGFBI gene were amplified by PCR. The products were directly sequenced and compared with GenBank database to identify potential mutation. Bioinformatic analysis was carried out to predict the effect of mutation on proteins. A heterozygous mutation (p.R124C) was found in exon 4 of the TGFBI gene in all patients from the pedigree but not among unaffected members. The mode of inheritance of corneal dystrophy in this pedigree was identified as autosomal dominant. Bioinformatics analysis predicted that the p.R124C mutation may be functionally deleterious. The phenotype of corneal dystrophy in the pedigree was determined to be LCD I type. The p.R124C mutation of the TGFBI gene probably underlies the pathogenesis of LCD in this Chinese pedigree. Genetic testing can facilitate proper diagnosis of this type of corneal dystrophy.


Influence of exogenous corticosterone on testicular function and mating behavior of Nigerian indigenous cocks.
In bridging the knowledge gap on stress physiology of Nigerian indigenous chickens, this study investigated the effect of exogenous corticosterone (eCORT) as stress inducing agent on the testicular function and mating behavior of Nigerian indigenous cocks. Twenty-four (24) cocks and one hundred and forty four (144) hens (mating ratio of 1 cock: 6 hens) were grouped into four and assigned to each of the four eCORT treatments (0, 2, 4 and 6 mgeCORT/KgBW) daily for 14 days. Semen samples were collected on days 0, 7 and 14 and analyzed for semen volume (SV), progressive sperm motility (PSM), membrane integrity (MI) and sperm abnormality (SA). Mating behaviors were monitored on days 3, 5 and 8. Blood samples, for hormonal (Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) Testosterone (TEST) and stress analysis (heterophil/lymphocyte ratio, H/L) were collected from brachial vein on days 7 and 14. On day 15, cocks were euthanized and testes harvested for histomorphometry. Data were analyzed using multivariate analysis, one-way ANOVA and Kruskal-Wallis tests all in SPSS 23. Administration of 4 mgeCORT/KgBW declined (P<0.05) PSM while 4 mgeCORT/KgBW and 6 mgeCORT/KgBW cocks had reduced (P<0.05) SV and MI with increased SA. Compared to baseline values, progressive sperm motility of cocks administered 6 mgeCORT for 7 and 14 days decreased (P<0.05) by 57.5% and 52.4%, respectively. Exogenous CORT had no significant (P>0.05) influence on the mating behaviors, H/L ratio, FSH and TEST. However, 2 mgeCORT/KgBW enhanced LH levels. Administration of eCORT did not affect the testicular epithelial height and seminiferous tubular diameter. In conclusion, optimal stress induced by eCORT impaired semen quality but with less impact on reproductive hormones, H/L and mating behaviors of intensively raised Nigerian indigenous cocks.


Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial.
Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM). The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model. A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15-2.01, p < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61-1.25) in participants with T2DM and 0.64 (0.51-0.80) in participants without diabetes (pinteraction = 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group (p = 0.10). In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.


Assessing the Influence of Failed Implant Reconstruction on Patient Satisfaction and Decision Regret after Salvage Free-Flap Breast Reconstruction.
Free-flap breast reconstruction after failed implant reconstruction is associated with improved patient outcomes. How the level of satisfaction achieved compares between patients with and without previously failed implant reconstruction remains unknown. The aim of this study was to assess the influence of prior failed implant-based reconstruction on long-term patient-reported outcomes after free-flap breast reconstruction. All patients undergoing free-flap breast reconstruction between 2015 and 2019 were identified. Patient satisfaction using the BREAST-Q and decisional regret using the Decision Regret Scale were compared between patients with and without a history of implant breast reconstruction. Overall, 207 patients were contacted and 131 completed the BREAST-Q and Decision Regret Scale. A total of 23 patients had a history of failed implant-based reconstruction requiring free-flap-flap salvage, most commonly due to infection (39.1%), chronic pain (34.8%), capsular contracture (26%), and implant malposition (26.1%). Following definitive free-flap reconstruction, patients with prior failed implant reconstruction had significantly lower BREAST-Q scores for satisfaction with breast (61.2 ± 16.7 vs. 70.4 ± 18.7; p = 0.04) and sexual well-being (38.5 ± 18.2 vs. 52.8 ± 24.7; p = 0.01) and reported higher decision regret (19.1 ± 18.6 vs. 9.6 ± 15.6, respectively). There were no significant differences for psychosocial well-being (p = 0.67), physical well-being (chest; p = 0.27), and physical well-being (abdomen; p = 0.91). A history of failed implant-based reconstruction is associated with reduced satisfaction and increased decision regret with the final reconstructive outcome. This data underscores the importance of appropriate patient selection at the initial consultation, and informed preoperative counseling regarding long-term outcomes in patients presenting for free-flap reconstruction after a failed implant-based reconstruction.


Development of a Data-Independent Targeted Metabolomics Method for Relative Quantification Using Liquid Chromatography Coupled with Tandem Mass Spectrometry.
Quantitative metabolomics approaches can significantly improve the repeatability and reliability of metabolomics investigations but face critical technical challenges, owing to the vast number of unknown endogenous metabolites and the lack of authentic standards. The present study contributes to the development of a novel method known as "data-independent targeted quantitative metabolomics" (DITQM), which was used to investigate the label-free quantitative metabolomics of multiple known and unknown metabolites in biofluid samples. This approach initially involved the acquisition of MS/MS data for all metabolites in biosamples using a sequentially stepped targeted MS/MS (sst-MS/MS) method, in which multiple product ion scans were performed by selecting all ions in the targeted mass ranges as the precursor ions. Subsequently, scheduled multiple reaction monitoring (MRM) by LC-MS/MS of the metabolome was established for 1658 characteristic ion pairs of 1324 metabolites. For sensitive and accurate quantification of these metabolites, mixed calibration curves were generated using sequentially diluted standard reference plasma samples using established MRM methods. Relative concentrations of all metabolites in each sample were calculated without using individual authentic standards. To evaluate the reliability and applicability of this new method, the performance of DITQM was validated by comparison to absolute quantification of 12 acylcarnitines using authentic standards and traditional metabolomics analysis for lung cancer. The results proved that the DITQM protocol is more reliable and can significantly improve clustering effects and repeatability in biomarker discovery. In this study, we established a novel methodology to standardize and quantify large-scale metabolome, providing a new choice for metabolomics research and its clinical applications.


Assessing the Power of Exome Chips.
Genotyping chips for rare and low-frequent variants have recently gained popularity with the introduction of exome chips, but the utility of these chips remains unclear. These chips were designed using exome sequencing data from mainly American-European individuals, enriched for a narrow set of common diseases. In addition, it is well-known that the statistical power of detecting associations with rare and low-frequent variants is much lower compared to studies exclusively involving common variants. We developed a simulation program adaptable to any exome chip design to empirically evaluate the power of the exome chips. We implemented the main properties of the Illumina HumanExome BeadChip array. The simulated data sets were used to assess the power of exome chip based studies for varying effect sizes and causal variant scenarios. We applied two widely-used statistical approaches for rare and low-frequency variants, which collapse the variants into genetic regions or genes. Under optimal conditions, we found that a sample size between 20,000 to 30,000 individuals were needed in order to detect modest effect sizes (0.5% < PAR > 1%) with 80% power. For small effect sizes (PAR <0.5%), 60,000-100,000 individuals were needed in the presence of non-causal variants. In conclusion, we found that at least tens of thousands of individuals are necessary to detect modest effects under optimal conditions. In addition, when using rare variant chips on cohorts or diseases they were not originally designed for, the identification of associated variants or genes will be even more challenging.