Calcium fluxes and contractility in isolated guinea pig atrium: effect of A23187.
The Ca2+ ionophore A23187 (10(-6) to 3 X 10(-5) M) increased the force of contraction is isolated guinea pig atria. In individual twitches, peak tension, maximum rate of tension development, time to peak tension, and total twitch duration were all increased by A23187. Tripelennamine, indomethacin, and atropine did not significantly alter the inotropic effect of A23187. Serotonin produced changes in individual twitches that differed qualitatively and quantitatively from those of A23187. Therefore, the inotropic action of A23187 is probably not mediated by release of endogenous histamine, prostaglandins, acetylcholine, or serotonin. 45Ca influx and efflux were increased by A23187. The enhanced 45Ca efflux exceeded that which would be predicted if the ionophore acted only to increase the passive Ca2+ permeability of the myocardial cell membrane. These results suggest that A23187 facilitates the entry of extracellular Ca2+ into the myocardial cell and the release of intracellular Ca2+ stores into the myoplasm. The resultant increase in intracellular Ca2+ activity could account for the positive inotropic action of A23187.


Meiotic cellular rejuvenation is coupled to nuclear remodeling in budding yeast.
Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors - including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material - are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and aged cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly, de novo generation of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.


Low impact weight-bearing exercise in an upright posture increases the activation of two key local muscles of the lumbo-pelvic region.
To date, a range of exercises have been used to improve the function of the lumbar multifidus (LM) and transversus abdominis (TrA) muscles in people with low back pain, but uncertainty remains as to what exactly constitutes meaningful LM and TrA training. We examined the effects of exercising with a new device which combines weight-bearing, an unstable base of support (BOS) (feet), an upright posture with a relatively stable lumbo-pelvic area, and functional lower limb movement, with the aim of exploring which of these elements may be effective, in increasing LM and TrA muscle activity. Twelve non-symptomatic participants had ultrasound images taken of their LM and TrA during a range of conditions, including rest, traditional exercise approaches to LM and TrA recruitment, and exercising on the new device. Our results indicate that an unstable BOS on its own is not enough to increase LM and TrA activity, and that a combination of weight-bearing, an unstable BOS (feet), an upright posture with a relatively stable lumbo-pelvic area, and functional lower limb movement is most effective at increasing LM and TrA activity. This way of exercising appears to recruit LM more effectively than the widely used "swelling" of LM, and to cause automatic TrA and LM recruitment. Importantly, our findings also indicate LM and TrA may have slightly different roles during trunk stabilisation.


Healthy HLA-DQ2.5+ Subjects Lack Regulatory and Memory T Cells Specific for Immunodominant Gluten Epitopes of Celiac Disease.
Celiac disease (CD) is an HLA-associated disorder characterized by a harmful T cell response to dietary gluten. It is not understood why most individuals who carry CD-associated HLA molecules, such as HLA-DQ2.5, do not develop CD despite continuous gluten exposure. In this study, we have used tetramers of HLA-DQ2.5 bound with immunodominant gluten epitopes to explore whether HLA-DQ2.5(+) healthy individuals mount a specific CD4(+) T cell response to gluten. We found that gluten tetramer-binding memory cells were rare in blood of healthy individuals. These cells showed lower tetramer-binding intensity and no signs of biased TCR usage compared with gluten tetramer-binding memory T cells from patients. After sorting and in vitro expansion, only 18% of the tetramer-binding memory cells from healthy subjects versus 79% in CD patients were gluten-reactive upon tetramer restaining. Further, T cell clones of tetramer-sorted memory cells of healthy individuals showed lower gluten-specific proliferative responses compared with those of CD patients, indicating that tetramer-binding memory cells in healthy control subjects may be cross-reactive T cells. In duodenal biopsy specimens of healthy control subjects, CD4(+) T cells were determined not to be gluten reactive. Finally, gluten tetramer-binding cells of healthy individuals did not coexpress regulatory T cell markers (Foxp3(+) CD25(+)) and cultured T cell clones did not express a cytokine profile that indicated immune-dampening properties. The results demonstrate that healthy HLA-DQ2.5(+) individuals do not mount a T cell response to immunodominant gluten epitopes of CD.


Antitumor Activities in Mouse Xenograft Models of Canine Mammary Gland Tumor by Defucosylated Mouse-Dog Chimeric Anti-Epidermal Growth Factor Receptor Antibody (E134Bf).
The epidermal growth factor receptor (EGFR) contributes to tumor malignancy through gene amplification and/or protein overexpression. In our previous study, we developed an anti-human EGFR (hEGFR) monoclonal antibody (mAb), clone EMab-134 (mouse IgG1, kappa), which specifically detects both hEGFR and dog EGFR (dEGFR). The defucosylated mouse IgG2a version of EMab-134 exhibits antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells and antitumor activities in mouse xenografts of CHO/dEGFR cells. In this study, we produced a defucosylated mouse-dog chimeric anti-EGFR mAb (E134Bf), and the reactivity of E134Bf against a canine mammary gland tumor cell line (SNP) was examined by flow cytometry. Furthermore, E134Bf highly exerted ADCC and CDC for SNP cells. The administration of E134Bf with canine mononuclear cells significantly suppressed the SNP xenograft growth. These results suggest that E134Bf exerts antitumor effects against dEGFR-expressing canine mammary gland tumors and could be valuable as part of an antibody treatment regimen for them.


Recurrent Acute Pancreatitis in a Patient with COVID-19 Infection.
BACKGROUND The novel COVID-19 disease has infected more than 2 million people worldwide, causing more than 120 000 deaths. While the disease is known to primarily affect the respiratory system, gastrointestinal manifestations can also occur. However, little is known about the development of acute pancreatitis in COVID-19. The present report highlights a patient with no precipitating risk factors for pancreatitis who presented with recurring acute pancreatitis following the diagnosis of SARS-CoV-2 infection. CASE REPORT An otherwise healthy 38-year-old man presented to the Emergency Department (ED) with fever and epigastric pain. Laboratory testing revealed a lipase level of 10 255 ukat/L. An abdominal ultrasound showed no gallstones. After ruling out the possible causes of acute pancreatitis, a diagnosis of idiopathic acute pancreatitis was made. He received conservative management and was discharged home after being medically stabilized. Of note, the patient tested positive for SARS-CoV-2 infection at a local testing center 1 week prior to presenting to the ED. One week following the discharge, the patient returned with recurrent severe epigastric pain. Laboratory testing showed a lipase level of 20 320 ukat/L. An abdominal CT revealed acute pancreatitis. Further workups, including abdominal ultrasound, hepatitis serology, and immunoglobulin G for autoimmune pancreatitis, were unrevealing. Repeated SARS-CoV-2 testing produced positive results. CONCLUSIONS The temporal relationship between clinical presentation of acute pancreatitis and SARS-CoV-2 infection in this patient with no precipitating risk factors for pancreatitis suggests COVID-19-associated acute pancreatitis. Our review of the literature found a handful of reported cases of acute pancreatitis in patients with coexisting SARS-CoV-2 infection, and this report presents the first presumptive case of COVID-19-associated recurring acute pancreatitis.


Granick revisited: Synthesizing evolutionary and ecological evidence for the late origin of bacteriochlorophyll via ghost lineages and horizontal gene transfer.
Photosynthesis-both oxygenic and more ancient anoxygenic forms-has fueled the bulk of primary productivity on Earth since it first evolved more than 3.4 billion years ago. However, the early evolutionary history of photosynthesis has been challenging to interpret due to the sparse, scattered distribution of metabolic pathways associated with photosynthesis, long timescales of evolution, and poor sampling of the true environmental diversity of photosynthetic bacteria. Here, we reconsider longstanding hypotheses for the evolutionary history of phototrophy by leveraging recent advances in metagenomic sequencing and phylogenetics to analyze relationships among phototrophic organisms and components of their photosynthesis pathways, including reaction centers and individual proteins and complexes involved in the multi-step synthesis of (bacterio)-chlorophyll pigments. We demonstrate that components of the photosynthetic apparatus have undergone extensive, independent histories of horizontal gene transfer. This suggests an evolutionary mode by which modular components of phototrophy are exchanged between diverse taxa in a piecemeal process that has led to biochemical innovation. We hypothesize that the evolution of extant anoxygenic photosynthetic bacteria has been spurred by ecological competition and restricted niches following the evolution of oxygenic Cyanobacteria and the accumulation of O2 in the atmosphere, leading to the relatively late evolution of bacteriochlorophyll pigments and the radiation of diverse crown group anoxygenic phototrophs. This hypothesis expands on the classic "Granick hypothesis" for the stepwise evolution of biochemical pathways, synthesizing recent expansion in our understanding of the diversity of phototrophic organisms as well as their evolving ecological context through Earth history.


Heat wave impact on morbidity and mortality in the elderly population: a review of recent studies.
The on-going climate change is predicted to yield a growing number of extreme climate events which will increase in both intensity and frequency. Increased longevity is changing society's demographics. It is very likely this will have a direct impact on population health. Many studies have previously shown that the elderly in a society are among the most vulnerable to heat waves. With a rapidly growing number of publications on this subject the objective was to review the recent literature for research regarding the impact of heat waves and elevated temperature on the elderly with regards to mortality and morbidity. PubMed was searched to identify studies published in English between 1st of January 2008 and 31st of December 2010 using the following key words: heat wave, mortality, morbidity, elderly and temperature. The relationship between high temperature and mortality and/or morbidity had to be studied. Results for the elderly had to be provided. Six studies of temperature-morbidity-relationship were found and 24 studies of temperature-mortality-relationship. Studies consistently reported increases in cardiovascular and respiratory mortality, as appeared also respiratory admissions to do during hot days and heat waves. However, the number of studies on morbidity published was much fewer. Few studies reported social, medical and environmental susceptibility factors. Future research should focus on studying susceptibilities and to non-fatal events which are not as studied as mortality. Studies on the modification of type of urban environment, housing and mortality and morbidity in the elderly population are also needed.


Class III polyhydroxybutyrate synthase: involvement in chain termination and reinitiation.
Polyhydroxybutyrate (PHB) synthase catalyzes the polymerization of (R)-3-hydroxybutyryl-CoA (CoA = coenzyme A) into high molecular weight PHB. Recombinant wild-type (wt) class III synthase from Allochromatium vinosum (PhaCPhaE(Av)), antibodies to this synthase and to PHB, and [(14)C]hydroxybutyryl-CoA (HB-CoA) have been used to detect oligomeric hydroxybutyrate (HB) units covalently bound to the synthase using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Although a distribution of products is typically observed, short (HB)(n)-bound synthases (designated species I) are most prevalent at low substrate to enzyme (S/E) ratios. Species I is similar to (HB)(n)-PhaC(Av) (n = 3-10 at minimum) recently identified using D302A-PhaCPhaE(Av) (Tian, J., Sinskey, A. J., and Stubbe, J. (2005) Biochemistry 44, 1495-1503). Species I is shown to be an intermediate in the elongation process of PHB synthesis in vitro. The reaction catalyzed by the wt synthase in vitro was further studied under two sets of conditions: at high (70000) and low (<200) S/E ratios. At high S/E ratios, kinetic analysis of the reaction of HB-CoA with the wt synthase monitored using antibodies to PhaCPhaE(Av) and Western blotting revealed the disappearance of PhaC(Av) at early time points and its reappearance as the molecular weight of the PHB approached 1.8 MDa. At low S/E ratios, species I was observed to increase with time after complete consumption of all of the HB-CoA. The results from studies under both sets of conditions suggest that an inherent property of the synthase is chain termination and reinitiation.


Dendritic cells: a spot on sialic Acid.
Glycans decorating cell surface and secreted proteins and lipids occupy the juncture where critical host-host and host-pathogen interactions occur. The role of glycan epitopes in cell-cell and cell-pathogen adhesive events is already well-established, and cell surface glycan structures change rapidly in response to stimulus and inflammatory cues. Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how glycans and their changes contribute to the overall immune response remains poorly defined. Sialic acids are unique sugars that usually occupy the terminal position of the glycan chains and may be modified by external factors, such as pathogens, or upon specific physiological cellular events. At cell surface, sialic acid-modified structures form the key fundamental determinants for a number of receptors with known involvement in cellular adhesiveness and cell trafficking, such as the Selectins and the Siglec families of carbohydrate recognizing receptors. Dendritic cells (DCs) preside over the transition from innate to the adaptive immune repertoires, and no other cell has such relevant role in antigen screening, uptake, and its presentation to lymphocytes, ultimately triggering the adaptive immune response. Interestingly, sialic acid-modified structures are involved in all DC functions, such as antigen uptake, DC migration, and capacity to prime T cell responses. Sialic acid content changes along DC differentiation and activation and, while, not yet fully understood, these changes have important implications in DC functions. This review focuses on the developmental regulation of DC surface sialic acids and how manipulation of DC surface sialic acids can affect immune-critical DC functions by altering antigen endocytosis, pathogen and tumor cell recognition, cell recruitment, and capacity for T cell priming. The existing evidence points to a potential of DC surface sialylation as a therapeutic target to improve and diversify DC-based therapies.


Regionalization of trauma care.
A massive shift of patients to relatively specialized types of care has occurred. Until recently these patients had been treated in local centers with good results and at much less expense. The issue of the loss of moral authority at the local level is not insignificant. One cause for optimism has been the good relationship with neurosurgeons at several local trauma centers. This has allowed for most head injury patients to be treated locally, though this is not reflected in these data, as these patients were not transferred.


Erdosteine protects HEI-OC1 auditory cells from cisplatin toxicity through suppression of inflammatory cytokines and induction of Nrf2 target proteins.
Cisplatin has many adverse effects, which are a major limitation to its use, including ototoxicity, neurotoxicity, and nephrotoxicity. This study aims to elucidate the protective mechanisms of erdosteine against cisplatin in HEI-OC1 cells. Pretreatment with erdosteine protects HEI-OC1 cells from cisplatin-medicated apoptosis, which is characterized by increase in nuclear fragmentation, DNA laddering, sub-G0/G1 phase, H2AX phosphorylation, PARP cleavage, and caspase-3 activity. Erdosteine significantly suppressed the production of reactive nitrogen/oxygen species and pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in cisplatin-treated cells. Studies using pharmacologic inhibitors demonstrated that phosphatidylinositol-3-kinases (PI3K) and protein kinase B (Akt) have protective roles in the action of erdosteine against cisplatin in HEI-OC1 cells. In addition, pretreatment with erdosteine clearly suppressed the phosphorylation of p53 (Ser15) and expression of p53-upregulated modulator of apoptosis. Erdosteine markedly induces expression of NF-E2-related factor 2 (Nrf2), which may contribute to the increase in expression of glutathione redox genes γ-l-glutamate-l-cysteine-ligase catalytic and γ-l-glutamate-l-cysteine-ligase modifier subunits, as well as in the antioxidant genes HO-1 and SOD2 in cisplatin-treated HEI-OC1 cells. Furthermore, the increase in expression of phosphorylated p53 induced by cisplatin is markedly attenuated by pretreatment with erdosteine in the mitochondrial fraction. This increased expression may inhibit the cytosolic expression of the apoptosis-inducing factor, cytochrome c, and Bax/Bcl-xL ratio. Thus, our results suggest that treatment with erdosteine is significantly attenuated cisplatin-induced damage through the activation of Nrf2-dependent antioxidant genes, inhibition of pro-inflammatory cytokines, activation of the PI3K/Akt signaling, and mitochondrial-related inhibition of pro-apoptotic protein expression in HEI-OC1 auditory cells.


Peripheral T-lymphocytes in juvenile-onset diabetics (JOD) and in maternity-onset diabetics (MOD).
The percentage and absolute number per mm.3 of peripheral T-lymphocytes were determined in 11 juvenile-onset diabetics (JOD), in 21 maturity-onset diabetics (MOD), and in 18 normal subjects (NS). The percentage was significantly lower in JOD (38.1) than in MOD (57.2) and NS (56.5). The absolute T-lymphocytes number per mm.3 was significantly lower in JOD (833) than in NS (1,260); this was also true for JOD as against MOD (1,026), even if the difference was not statistically significant. No difference was found between MOD and NS, or between MOD on oral therapy and on insulin treatment. The decrease of peripheral T-lymphocytes in JOD was not related to associated illness or drugs. The data presented suggest the possibility of an altered cell-mediated immunity in juvenile-onset diabetics.


UVA1 phototherapy: a review of mechanism and therapeutic application.
Ultraviolet radiation (UVR) phototherapy has been associated with both deleterious and beneficial effects to patients with both localized and systemic skin disorders. Phototherapy is advantageous in diseases of the epidermis and dermis, as it provides the most direct approach minimizing systemic side effects. Most recently, ultraviolet A1 (UVA1) phototherapy has emerged as a specific UVR phototherapeutic mechanism. It has shown to be therapeutic in a number of sclerosing skin conditions and other dermatitides, in many cases proving to be more effective than other phototherapy modalities. Treatment advantages of UVA1 phototherapy include the ability to penetrate into the deep layers of the skin to affect changes on disease-causing T cells, as well as activation of endothelial cells to promote neovascularization. UVA1 therapy also has been shown to be relatively free of side effects associated with other phototherapy regimens, including erythema and cellular transformation. These properties make UVA1 phototherapy an important treatment option for many debilitating skin conditions.


Differentiation of faecal Escherichia coli from human and animal sources by random amplified polymorphic DNA-PCR (RAPD-PCR).
In this study the assessment of randomly amplified polymorphic DNA (RAPD) analysis was established as a molecular epidemiological tool. RAPD analysis was performed to differentiate faecal Escherichia coli isolates from human and animal sources. E. coli strains (128) were isolated from human and animal faeces (from cattle and sheep). Genomic DNA was extracted and randomly amplified polymorphic DNA-PCR (RAPD-PCR) fingerprinting was performed. Seven arbitrary primers were tested with a view to discriminating between E. coli isolates from humans and E. coli isolates from animals. RAPD profiles were analysed with hierarchical cluster analysis using an unweighted pair group method. RAPD profiles obtained with three of the tested primers (1247, 1290 and 1254) established a distinct differentiation between E. coli isolates from humans and E. coli from animals. Low levels of misclassification and high levels of specificity make RAPD a sensitive, efficient and reliable means of distinguishing closely related strains.


Multivariate optimization of a new LC-MS/MS method for the determination of 156 pesticide residues in milk and dairy products.
Pesticides are widely utilized worldwide to control undesirable life forms during the planting procedure in agriculture. But they can pollute the nature and jeopardize human wellbeing. Additionally, on account of high resistance and biological activity; pesticides are able to accumulate in living organs and lead to acute and long-term negative effects along with toxicity. Milk and dairy products constitute an important part of a humans' diet since they contain fundamental supplements and nutrients, however they may also be the source of unhealthy components including pesticides. Therefore efficient, accurate and sensitive determination methods must be improved to quantify pesticide residues in these food samples. Multivariate optimization strategy was employed to optimize an efficient and robust liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for the determination of 156 pesticide residues in milk and dairy products. Three independent variables considered and their levels in the Box-Behnken design were as follows: initial percentage of eluent A in mobile phase (30, 40, 50%), flow rate of the mobile phase (0.1, 0.2, 0.3 mL min-1 ), and ammonium formate concentration in mobile phase (0.0, 0.5, 1.0 mmol L-1 ). Under optimized conditions, average recoveries of target analytes were obtained in the range of 70.38% to 119.04%. Detection and quantification limits ranged from 0.06 to 2.70 μg kg-1 and from 0.22 to 8.10 μg kg-1 , respectively. The validated method was successfully implemented to the analysis of 20 milk and dairy products including cream, cheese and yogurt. This method could be applied in many laboratories to reduce analysis time and cost. © 2020 Society of Chemical Industry.


Cellular and molecular responses of adult testis to changes in nutrition: novel insights from the sheep model.
This review explores the cellular and molecular mechanisms that regulate spermatogenesis in the post-pubertal testis that is regressing in response to mild undernutrition, using the sexually mature male sheep as a model. Testis regression leads to reductions in daily sperm production and in the quality of ejaculated spermatozoa (poorer movement, DNA damage). There is also a reduction in spermatogenic efficiency that appears to be caused, at least partially, by increases in germ cell apoptosis. Sertoli cell number does not change with testis regression, although about 1% of Sertoli cells do appear to retain proliferative ability after puberty. On the other hand, Sertoli cell function is disrupted during testis regression, as evidenced by a disorganization of tight junctions and indications that cell differentiation and maturation are reversed. Disrupted Sertoli cell function can explain, at least partially, the increase in germ cell apoptosis and any decrease in the rate of spermatogenesis, the two major contributors to spermatogenic efficiency. These outcomes seem to be mediated by changes in two RNA-based processes: (i) the expression of small non-coding RNAs that are involved in the regulation of Sertoli cell function, spermatogenesis and germ cell apoptosis and (ii) alternative pre-mRNA splicing that affects the regulation of spermatogenesis but does not appear to affect germ cell apoptosis, at least during testis progression induced by undernutrition in the male sheep. These research outcomes can be extended to other animal models and are relevant to issues in human male fertility.


Repair of DNA and chromosome breaks in cells exposed to SR 4233 under hypoxia or to ionizing radiation.
3-Amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) is a bioreductive anticancer drug which has a high selective toxicity to hypoxic cells. We have characterized the DNA and chromosome damage in wild-type Chinese hamster ovary (CHO) cells and mutant XR-1 cells after exposure to SR 4233 under hypoxia and compared it to the damage produced by ionizing radiation (gamma-rays). Using the technique of pulsed field gel electrophoresis, we found that the kinetics of rejoining of DNA double-strand breaks in CHO cells after treatment with SR 4233 was concentration dependent, varying from 95% (less than 50 microM) to 10% (200 microM) by 24 h. This contrasted with the dose-independent kinetics exhibited in cells after gamma-ray exposure. XR-1 cells were deficient in rejoining double-strand breaks produced by either SR 4233 or gamma-rays. XR-1 cells were 2-fold more sensitive than wild-type CHO cells to SR 4233 but were 10-fold more sensitive than CHO to gamma-rays. These results suggested that DNA double-strand breaks are involved in hypoxic cell killing by SR 4233, but the specific type of lesion produced is not identical with that causing cell killing by gamma-rays. To further investigate this, we measured chromosome breaks in CHO cells by premature chromosome condensation after equitoxic doses of SR 4233 under hypoxia and gamma-rays. SR 4233 produced lower initial but similar final (after 6 h of repair) numbers of chromosome breaks compared to gamma-rays at equitoxic doses. These results suggest that, at low doses, chromosome breaks can entirely account for hypoxic cell killing by SR 4233 and that chromosome breaks produced by SR 4233 are more damaging and/or more difficult to repair than those produced by gamma-rays.


Tuning the mind: Exploring the connections between musical ability and executive functions.
A growing body of research suggests that musical experience and ability are related to a variety of cognitive abilities, including executive functioning (EF). However, it is not yet clear if these relationships are limited to specific components of EF, limited to auditory tasks, or reflect very general cognitive advantages. This study investigated the existence and generality of the relationship between musical ability and EFs by evaluating the musical experience and ability of a large group of participants and investigating whether this predicts individual differences on three different components of EF - inhibition, updating, and switching - in both auditory and visual modalities. Musical ability predicted better performance on both auditory and visual updating tasks, even when controlling for a variety of potential confounds (age, handedness, bilingualism, and socio-economic status). However, musical ability was not clearly related to inhibitory control and was unrelated to switching performance. These data thus show that cognitive advantages associated with musical ability are not limited to auditory processes, but are limited to specific aspects of EF. This supports a process-specific (but modality-general) relationship between musical ability and non-musical aspects of cognition.


Concurrent working memory task decreases the Stroop interference effect as indexed by the decreased theta oscillations.
Working memory (WM) tasks may increase or decrease the interference effect of concurrently performed cognitive control tasks. However, the neural oscillatory correlates of this modulation effect of WM on the Stroop task are still largely unknown. In the present study, behavioral and electroencephalographic (EEG) data were recorded from 32 healthy participants during their performance of the single Stroop task and the same task with a concurrent WM task. We observed that the Stroop interference effect represented in both response times (RTs) and theta-band event-related spectral perturbation (ERSP) magnitude reduced under the dual-task condition compared with the single-task condition. The reduction of interference in theta-band ERSP was further positively correlated with interference reduction in RTs, and was mainly explained by the source in the left middle frontal gyrus. In conclusion, the present study suggests that the effect of concurrent WM tasks on the reduction of the Stroop interference effect can be indexed by EEG oscillations in theta-band rhythm in the centro-frontal regions and this modulation was mediated by the reduced cognitive control under the concurrent WM task.


Modeling Obesity-Driven Pancreatic Carcinogenesis-A Review of Current In Vivo and In Vitro Models of Obesity and Pancreatic Carcinogenesis.
Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy with a 5-year survival rate below 10%, thereby exhibiting the worst prognosis of all solid tumors. Increasing incidence together with a continued lack of targeted treatment options will cause PDAC to be the second leading cause of cancer-related deaths in the western world by 2030. Obesity belongs to the predominant risk factors for pancreatic cancer. To improve our understanding of the impact of obesity on pancreatic cancer development and progression, novel laboratory techniques have been developed. In this review, we summarize current in vitro and in vivo models of PDAC and obesity as well as an overview of a variety of models to investigate obesity-driven pancreatic carcinogenesis. We start by giving an overview on different methods to cultivate adipocytes in vitro as well as various in vivo mouse models of obesity. Moreover, established murine and human PDAC cell lines as well as organoids are summarized and the genetically engineered models of PCAC compared to xenograft models are introduced. Finally, we review published in vitro and in vivo models studying the impact of obesity on PDAC, enabling us to decipher the molecular basis of obesity-driven pancreatic carcinogenesis.


Effect of ascorbic acid, ethanol and acetone on adhesion between the treated fiber posts and composite resin cores.
The aim of the present study was to assess the effect of ascorbic acid, ethanol and acetone on microtensile bond strength between fiber posts pre-treated with hydrogen peroxide and composite resin cores. Twenty four fiber posts were pre-treated with 24% hydrogen peroxide and divided into 4 groups as follows: G1: no treatment, as control group; G2: treatment with 10% ascorbic acid solution for 5 minutes; G3: treatment with 70% ethanol solution for 5 minutes; and G4: treatment with 70% acetone solution for 5 minutes. Each fiber post was surrounded by a cylinder-shaped polyglass matrix which was subsequently filled with composite resin. Two sections from each sample were selected for microtensile test at a crosshead with speed of 0.5 mm/min. Statistical analyses were performed using one-way ANOVA and a post hoc Tukey HSD test. Fractured surfaces were observed under a stereomicroscope at ×20 magnification. The fractured surfaces of the specimens were observed and evaluated under a SEM. MEANS OF MICROTENSILE BOND STRENGTH VALUES (MPA) AND STANDARD DEVIATIONS IN THE GROUPS WERE AS FOLLOWS: G1: 9.70±0.81; G2: 12.62±1.80; G3: 16.60±1.93; and G4: 21.24±1.95. G4 and G1 had the highest and the lowest bond strength values, respectively. A greater bond strength value was seen in G3 compared to G2. There were significant differences between all the groups (P<.001). All the failures were of the adhesive mode. Application of antioxidant agents may increase microtensile bond strength between fiber posts treated with hydrogen peroxide and composite cores. Acetone increased bond strength more than ascorbic acid and ethanol.


Adaptive changes in sexual signalling in response to urbanization.
Urbanization can cause species to adjust their sexual displays, because the effectiveness of mating signals is influenced by environmental conditions. Despite many examples that show that mating signals in urban conditions differ from those in rural conditions, we do not know whether these differences provide a combined reproductive and survival benefit to the urban phenotype. Here we show that male túngara frogs have increased the conspicuousness of their calls, which is under strong sexual and natural selection by signal receivers, as an adaptive response to city life. The urban phenotype consequently attracts more females than the forest phenotype, while avoiding the costs that are imposed by eavesdropping bats and midges, which we show are rare in urban areas. Finally, we show in a translocation experiment that urban frogs can reduce risk of predation and parasitism when moved to the forest, but that forest frogs do not increase their sexual attractiveness when moved to the city. Our findings thus reveal that urbanization can rapidly drive adaptive signal change via changes in both natural and sexual selection pressures.


Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis.
Species of the genus Streptomyces are of major pharmaceutical interest because they synthesize a variety of bioactive secondary metabolites. We have determined the complete nucleotide sequence of the linear chromosome of Streptomyces avermitilis. S. avermitilis produces avermectins, a group of antiparasitic agents used in human and veterinary medicine. The genome contains 9,025,608 bases (average GC content, 70.7%) and encodes at least 7,574 potential open reading frames (ORFs). Thirty-five percent of the ORFs (2,664) constitute 721 paralogous families. Thirty gene clusters related to secondary metabolite biosynthesis were identified, corresponding to 6.6% of the genome. Comparison with Streptomyces coelicolor A3(2) revealed that an internal 6.5-Mb region in the S. avermitilis genome was highly conserved with respect to gene order and content, and contained all known essential genes but showed perfectly asymmetric structure at the oriC center. In contrast, the terminal regions were not conserved and preferentially contained nonessential genes.


Changing implicit attitudes toward smoking: results from a web-based approach-avoidance practice intervention.
Implicit attitudes have been shown to predict smoking behaviors. Therefore, an important goal is the development of interventions to change these attitudes. This study assessed the effects of a web-based intervention on implicit attitudes toward smoking and receptivity to smoking-related information. Smokers (N = 284) were recruited to a two-session web-based study. In the first session, baseline data were collected. Session two contained the intervention, which consisted of assignment to the experimental or control version of an approach-avoidance task and assignment to an anti-smoking or control public service announcement (PSA), and post-intervention measures. Among smokers with less education and with plans to quit, implicit attitudes were more negative for those who completed the approach-avoidance task. Smokers with more education who viewed the anti-smoking PSA and completed the approach-avoidance task spent more time reading smoking-related information. An approach-avoidance task is a potentially feasible strategy for changing implicit attitudes toward smoking and increasing receptivity to smoking-related information.


[Mechanism of development of erythrocytosis in spontaneous arterial hypertension in rats].
Rats with spontaneous hypertension versus normotensive rats showed the development of erythrocytosis, an intensification of the erythropoietic properties of the blood plasma and an increase of the 2,3-DPG concentration in the red blood cells. An enhanced production of erythropoietin, a humoral stimulator of erythropoiesis, seems to be one of the causes of the erythrocytosis development in spontaneously hypertensive rats. An increase in the 2,3-DPG concentration in the erythrocytes is an important physiological mechanism ensuring the appropriate oxygen supply to tissues.


Collateral outcomes in e-mental health: a systematic review of the evidence for added benefits of computerized cognitive behavior therapy interventions for mental health.
E-mental health is a growing research field and an increasing number of computerized cognitive behavior therapy (cCBT) interventions are available for numerous mental health issues. Such interventions are often claimed to have added benefits, or collateral outcomes, when compared with traditional delivery platforms. Our aim was to systematically review the evidence of the cost-effectiveness, geographic flexibility, time flexibility, waiting time for treatment, stigma, therapist time, effects on help-seeking and treatment satisfaction of cCBT interventions for mental health. The electronic databases Medline and Web of Science were searched for peer-reviewed controlled trials investigating collateral outcomes in computerized and internet-based CBT. The literature search identified 101 published papers (95 studies), which were included in this review. The results suggest that cCBT interventions are cost-effective and often cheaper than usual care. Limited evidence was found with regard to geographic flexibility, time flexibility, waiting time for treatment, stigma and the effects on help-seeking. Personal support in cCBT was found to take many forms, was not limited only to therapists, and seemed to increase treatment adherence and reduce attrition. Treatment satisfaction with cCBT was found to be high, but more research on attrition due to dissatisfaction is required. Although the results of this systematic review on the collateral outcomes provide support for the potential of cCBT, these outcomes need to be better assessed within individual e-mental health studies.


Cognitive Adaptations for n-person Exchange: The Evolutionary Roots of Organizational Behavior.
Organizations are composed of stable, predominantly cooperative interactions or n-person exchanges. Humans have been engaging in n-person exchanges for a great enough period of evolutionary time that we appear to have evolved a distinct constellation of species-typical mechanisms specialized to solve the adaptive problems posed by this form of social interaction. These mechanisms appear to have been evolutionarily elaborated out of the cognitive infrastructure that initially evolved for dyadic exchange. Key adaptive problems that these mechanisms are designed to solve include coordination among individuals, and defense against exploitation by free riders. Multi-individual cooperation could not have been maintained over evolutionary time if free riders reliably benefited more than contributors to collective enterprises, and so outcompeted them. As a result, humans evolved mechanisms that implement an aversion to exploitation by free riding, and a strategy of conditional cooperation, supplemented by punitive sentiment towards free riders. Because of the design of these mechanisms, how free riding is treated is a central determinant of the survival and health of cooperative organizations. The mapping of the evolved psychology of n-party exchange cooperation may contribute to the construction of a principled theoretical foundation for the understanding of human behavior in organizations.


Identification of potyviruses using the polymerase chain reaction with degenerate primers.
Local areas of conserved amino acid sequence in the replicase and coat proteins of potyviruses were used to select nucleotide sequences for use in the construction of sets of degenerate oligonucleotide primers for amplification of DNA fragments on potyvirus-specific templates in a combined assay of reverse transcription and the polymerase chain reaction (RT-PCR). Sequences selected for the construction of degenerate primers included the coat protein gene sequence of tulip breaking virus from lily, which is reported in this paper. It is shown that the degenerate primers support potyvirus-specific amplification, but do not support amplification on carlavirus and potexvirus templates. A panel consisting of definite and prospective members of the potyvirus group occurring in bulbous crops was subjected to the degenerate primer RT-PCR assay; amplified fragments were used in cross-hybridization experiments and restriction fragment length polymorphism analysis to detect relationships among these potyviruses. A partially characterized virus isolated from Gloriosa rothschildiana was positively identified as a potyvirus by specific amplification and subsequent sequence analysis of an amplified DNA fragment.


Recent patents on biclustering algorithms for gene expression data analysis.
In DNA microarray experiments, discovering groups of genes that share similar transcriptional characteristics is instrumental in functional annotation, tissue classification and motif identification. However, in many situations a subset of genes only exhibits a consistent pattern over a subset of conditions. Although used extensively in gene expression data analysis, conventional clustering algorithms that consider the entire row or column in an expression matrix can therefore fail to detect useful patterns in the data. Recently, biclustering has been proposed as a powerful computational tool to detect subsets of genes that exhibit consistent pattern over subsets of conditions. In this article, we review several recent patents in bicluster analysis, and in particular, highlight a recent patent from our group about a novel geometric-based biclustering method that handles the class of bicluster patterns with linear coherent variation across the row and/or column dimension. This class of bicluster patterns is of particular importance since it subsumes all constant, additive, and multiplicative bicluster patterns normally used in gene expression data analysis.


Monoclonal antibodies against viral determinants are not restricted to the K/D end of the major histocompatibility complex.
Monoclonal antibodies against lymphocytic choriomeningitis virus (LCMV), a natural, high-replicating, noncytolytic pathogen in mice, were obtained from fusions between myeloma cells and lymphoid cells of mice of different H-2 haplotypes at various times (4-24 d) after infection. Supernatants from growing hybridomas were tested in a RIA, and approximately 15% of all supernatants were positive when tested for specificity on infected vs. uninfected cells of different haplotypes. Upon retesting for specific fluorescence, only some RIA+ supernatants exhibited specific surface staining of acetone-fixed infected cells or unfixed infected cells. In all these experiments and using various detection methods we could not find antibodies with any preference of recognition of viral antigen in conjunction with the H-2 haplotype of the responder mouse. The absence of H-2 restricted antibodies after a primary virus infection in vivo, whether assayed by RIA or surface immunofluorescence, suggests that antibodies obtained in other experiments using infected tumor cells for induction and in the RIA may not represent the general case.


tRNA-dependent asparagine formation in prokaryotes: characterization, isolation and structural and functional analysis of a ribonucleoprotein particle generating Asn-tRNA(Asn).
In some living organisms the 20 aa-tRNA species participating in protein synthesis are not charged by a complete set of 20 aminoacyl-tRNA synthetases. In prokaryotes, the deficiency of asparaginyl- and/or glutaminyl-tRNA synthetases is compensated by another aminoacyl-tRNA synthetase of relaxed specificity that mischarges the orphan tRNA and by an enzyme that converts the amino acid into that homologous to the tRNA. In Thermus thermophilus Asn-tRNA(Asn) is formed indirectly via a two-step pathway whereby tRNA(Asn) is mischarged with Asp that will subsequently be amidated into Asn by an amidotransferase. The non-discriminating aspartyl-tRNA synthetase, the trimeric GatCAB tRNA-dependent amidotransferase and the tRNA(Asn) promoting this pathway assemble into a ribonucleoprotein particle termed transamidosome. This article deals with the methods and techniques employed to clone the genes encoding the enzymes and the tRNA involved in this pathway, to express them in Escherichia coli, to isolate them on a large scale, and to transcribe and produce mg quantities of pure tRNA(Asn)in vitro. The approaches designed especially for this system include (i) clustering of the ORFs encoding the subunits of the heterotrimeric GatCAB that are sprinkled in the genome into an artificial operon, and (ii) the self-cleavage of the tRNA(Asn) transcript starting with U in 5' position through fusion with a hammerhead ribozyme. Further, the crystallization of the free enzymes is described and the characterization of their assembly with tRNA(Asn) into a ribonucleoprotein particle, as well as the investigation of the catalytic mechanism of Asn-tRNA(Asn) formation by the complex are reported.


Elevated CA 19-9 is associated with worse survival in patients with resected ampullary adenocarcinoma.
The prognostic utility of Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) in ampullary adenocarcinoma is unclear. We sought to evaluate the association between initial tumor marker levels and survival in patients with resected ampullary adenocarcinoma. This was a single-institution, retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma from 1999 to 2021. CA 19-9 was assessed after biliary decompression. Contal and O'Quigley method determined optimal biomarker cutoff levels which were correlated with overall survival (OS) using the Kaplan-Meier method and Cox Proportional Hazards Regression. A total of 180 patients underwent pancreatoduodenectomy. Patients with CA 19-9 >100 U/mL had a shorter median OS (28 vs. 132 months, p < 0.001) compared to patients with CA 19-9 ≤ 100 U/mL at diagnosis. Survival was similar between pancreaticobiliary and intestinal tumor subtypes when CA 19-9 was >100 U/mL (OS:25 vs. 33 months, p = 0.415). By Cox regression analysis, CA 19-9 >100 U/mL was independently associated with worse OS (HR 2.8, p = 0.001). Preoperative CA 19-9 >100 U/mL was associated with shorter OS in patients with resected ampullary adenocarcinoma. CA 19-9 may be useful when counseling patients about prognosis or when considering the role of perioperative systemic therapy.


Human feeding biomechanics: performance, variation, and functional constraints.
The evolution of the modern human (Homo sapiens) cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA) to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes), the modern human craniofacial skeleton is (1) less well configured, or (2) better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting) side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint dislocation and constrained the maximum recruitment levels of the masticatory muscles on the balancing (non-biting) side of the head. Our results do not necessarily conflict with the hypothesis that anterior tooth (incisors, canines, premolars) biting could have been selectively important in humans, although the reduced size of the premolars in humans has been shown to increase the risk of tooth crown fracture. We interpret our results to suggest that human craniofacial evolution was probably not driven by selection for high magnitude unilateral biting, and that increased masticatory muscle efficiency in humans is likely to be a secondary byproduct of selection for some function unrelated to forceful biting behaviors. These results are consistent with the hypothesis that a shift to softer foods and/or the innovation of pre-oral food processing techniques relaxed selective pressures maintaining craniofacial features that favor forceful biting and chewing behaviors, leading to the characteristically small and gracile faces of modern humans.


Fetal Re-Identification in Multiple Pregnancy Ultrasound Images Using Deep Learning.
Ultrasound examinations during pregnancy can detect abnormal fetal development, which is a leading cause of perinatal mortality. In multiple pregnancies, the position of the fetuses may change between examinations. The individual fetus cannot be clearly identified. Fetal re-identification may improve diagnostic capabilities by tracing individual fetal changes. This work evaluates the feasibility of fetal re-identification on FETAL_PLANES_DB, a publicly available dataset of singleton pregnancy ultrasound images. Five dataset subsets with 6,491 images from 1,088 pregnant women and two re-identification frameworks (Torchreid, FastReID) are evaluated. FastReID achieves a mean average precision of 68.77% (68.42%) and mean precision at rank 10 score of 89.60% (95.55%) when trained on images showing the fetal brain (abdomen). Visualization with gradient-weighted class activation mapping shows that the classifiers appear to rely on anatomical features. We conclude that fetal re-identification in ultrasound images may be feasible. However, more work on additional datasets, including images from multiple pregnancies and several subsequent examinations, is required to ensure and investigate performance stability and explainability.Clinical relevance- To date, fetuses in multiple pregnancies cannot be distinguished between ultrasound examinations. This work provides the first evidence for feasibility of fetal re-identification in pregnancy ultrasound images. This may improve diagnostic capabilities in clinical practice in the future, such as longitudinal analysis of fetal changes or abnormalities.


Multiplexed computer-generated holograms with polygonal-aperture layouts optimized by genetic algorithm.
Using a novel genetic algorithm (GA) with a Lamarckian search we optimize the polygonal layout of a new type of multiplexed computer-generated hologram (MCGH) with polygonal apertures. A period ofthe MCGH is divided into cells, and the cell is further divided into polygonal apertures according to a polygonal layout, which is to be optimized. Among an ensemble of 1.21 x 10(24) possible polygonal layouts, we take a population of 102 solutions, which are coded as chromosomes of bits, and find the optimal solution with our GA. We introduce rank-based selection with cumulative normal distribution fitness, double crossover, exponentially decreasing mutation probability and Lamarckian downhill search with a small number of offspring chromosomes into our GA, which shows a rapid convergence to the global minimum of the cost function. In a second step of optimization the phase distributions over the subholograms in the MCGH are determined with our iterative subhologram design algorithm. Our MCGH designs show large-sie reconstructed images with high diffraction efficiency and low reconstruction error.


Simulation of future groundwater recharge using a climate model ensemble and SAR-image based soil parameter distributions - A case study in an intensively-used Mediterranean catchment.
We used observed climate data, an ensemble of four GCM-RCM combinations (global and regional climate models) and the water balance model mGROWA to estimate present and future groundwater recharge for the intensively-used Thau lagoon catchment in southern France. In addition to a highly resolved soil map, soil moisture distributions obtained from SAR-images (Synthetic Aperture Radar) were used to derive the spatial distribution of soil parameters covering the full simulation domain. Doing so helped us to assess the impact of different soil parameter sources on the modelled groundwater recharge levels. Groundwater recharge was simulated in monthly time steps using the ensemble approach and analysed in its spatial and temporal variability. The soil parameters originating from both sources led to very similar groundwater recharge rates, proving that soil parameters derived from SAR images may replace traditionally used soil maps in regions where soil maps are sparse or missing. Additionally, we showed that the variance in different GCM-RCMs influences the projected magnitude of future groundwater recharge change significantly more than the variance in the soil parameter distributions derived from the two different sources. For the period between 1950 and 2100, climate change impacts based on the climate model ensemble indicated that overall groundwater recharge will possibly show a low to moderate decrease in the Thau catchment. However, as no clear trend resulted from the ensemble simulations, reliable recommendations for adapting the regional groundwater management to changed available groundwater volumes could not be derived.


[Characteristics of reaction of the coronary vessels and metabolism of the myocardium in changing over from high to low frequency electric stimulation of the heart].
In 22 tests on an isolated dog's heart perfused from a donor the oxygen intake, coronary blood flow, oxyhemoglobin content in the coronary venous blood and arterio-venous difference were compared with a jumpwise and gradual depression of the electrostimulation of the heart rhythm from 4.5 down to 2.0-2.5 Hd. With an abrupt reduction of the contraction rhythm in the myocardium these persisted hypermetabolism outwardly resembling an acquintance of the oxygen debt, although the preceding work of the heart proceeded without any signs of hypoxia. There could be noted an elevated consumption of oxygen, an increased coronary circulation, a diminished utilization of lactic acid and even its ejection. Worthy of note is the fact that an elevated oxygen intake was ensured at the expense of the larger coronary circulation with a reduced extraction of oxygen, so that the saturation of the coronary venous blood with oxygen exceeded the initial values. With a gradual slowing down of the rhythm there were no manifestation of hypermetabolism: the consumption of oxygen returned back to its initial level, the coronary circulation decreased, while extraction of oxygen was rising. The data obtained are considered in the light of the metabolic hypothesis on the regulation of the vascular tone.


Pediatric fluctuating sensorineural hearing loss: problems in medical management.
To discuss the diagnosis and management of children with fluctuating sensorineural hearing loss, especially focusing on those problems dealing with autoimmune inner ear disease. A retrospective chart review of a large pediatric otolaryngology practice. A series of 40 children with progressive hearing losses was identified. Of that group, 22 children, aged 1.5 to 12.2 years at first audiogram, were considered to have fluctuating sensorineural hearing loss (FSNHL). Criteria for inclusion in the FSNHL group were threshold variations of 15 dB or more in at least one ear at two or more of the standard audiometric frequencies on at least 2 testing days. Charts were reviewed for age, sex, otologic history, laboratory evaluations, medical or surgical treatments, significant medical history, and family medical history. Twenty-two children met the criteria for fluctuating sensorineural hearing loss. Of those with fluctuating hearing loss, 15 were idiopathic, 3 had positive lymphocyte transformation tests (LTT) suggestive of autoimmune inner ear disease (AIED), and 4 had fistula on middle ear exploration. Average fluctuation for all groups was 29.1 dB. Average duration of fluctuations was 4.95 years. The majority of pediatric FSNHL cases (15 of 22) were idiopathic in nature. Of those FSNHL children with positive LTTs, only one was treated with steroid therapy. In the other patients with positive LTTs, parents or other physicians were often reluctant to treat, or the patient was lost to follow-up. Mean fluctuations varied substantially across all standard audiometric frequencies for all groups.


MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial.
Background Diffuse midline gliomas (DMG) are characterized by a high incidence of H3 K27 mutations and poorer outcome. The HERBY trial has provided one of the largest cohorts of pediatric DMGs with available radiologic, histologic-genotypic, and survival data. Purpose To define MRI and molecular characteristics of DMG. Materials and Methods This study is a secondary analysis of a prospective trial (HERBY; ClinicalTrials.gov identifier, NCT01390948) undertaken between October 2011 and February 2016. Among 121 HERBY participants, 50 had midline nonpontine-based tumors. Midline high-grade gliomas were reclassified into DMG H3 K27 mutant, H3 wild type with enhancer of zest homologs inhibitory protein overexpression, epidermal growth factor receptormutant, or not otherwise stated. The epicenter of each tumor and other radiologic characteristics were ascertained from MRI and correlated with the new subtype classification, histopathologic characteristics, surgical extent, and outcome parameters. Kaplan-Meier curves and log-rank tests were applied to determine and describe survival differences between groups. Results There were 42 participants (mean age, 12 years ± 4 [SD]; 23 girls) with radiologically evaluable thalamic-based DMG. Eighteen had partial thalamic involvement (12 thalamopulvinar, six anteromedial), 10 involved a whole thalamus, nine had unithalamic tumors with diffuse contiguous extension, and five had bithalamic tumors (two symmetric, three partial). Twenty-eight participants had DMG H3 K27 mutant tumors; there were no differences in outcome compared with other DMGs (n = 4). Participants who underwent major debulking or total or near-total resection had longer overall survival (OS): 18.5 months vs 11.4 months (P = .02). Enrolled participants who developed leptomeningeal metastatic dissemination before starting treatment had worse outcomes (event-free survival, 2.9 months vs 8.0 months [P = .02]; OS, 11.4 months vs 18.5 months [P = .004]). Conclusion Thalamic involvement of diffuse midline gliomas ranged from localized partial thalamic to holo- or bithalamic with diffuse contiguous spread and had poor outcomes, irrespective of H3 K27 subtype alterations. Leptomeningeal dissemination and less than 50% surgical resection were adverse risk factors for survival. Clinical trial registration no. NCT01390948 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Widjaja in this issue.


Activity in human medial temporal lobe associated with encoding process in spatial working memory revealed by magnetoencephalography.
Animal studies have suggested that working memory may be affected after lesions in the medial temporal lobe, although this assumption has not been corroborated by neuropsychological studies in humans. However, very recently, several functional neuroimaging studies in humans have successfully observed activation of the medial temporal lobe during working memory tasks. The main aim of this study was to investigate the contribution of the medial temporal lobe to the encoding process in spatial working memory. To address this issue we registered the neuromagnetic brain patterns of eight adult volunteers while they performed a spatial working memory task and more perceptual task using identical stimuli. After a initial phase (between 200 and 400 ms) without differences in activation, the medial temporal lobe showed a sustained activity, more evident in the right hemisphere, lasting up to 800 ms during the encoding stage of the spatial working memory task, while the activation in the perceptual task terminated earlier (approximately 400 ms after stimulus onset). The finding of a continued activation of the medial temporal lobe strongly suggests the contribution of this brain region to encoding operations in working memory.


Late Apical Recurrence of Choroidal Melanoma 10 Years after Successful Treatment with Brachytherapy.
To describe late apical relapse of a choroidal melanoma at the site of fine needle aspiration biopsy 10 years following successful treatment with 125I brachytherapy. Retrospective case report of a 78-year-old male presenting 10 years following successful 125I brachytherapy for a choroidal melanoma with a medium-sized nodular amelanotic tumor recurrence at the site of the prior tumor biopsy. Fundus photography and B-scan ultrasound documented the findings at presentation at our institution. The patient was followed closely for 8 weeks while information was retrieved from the treating institution. During this short period, there was significant apical tumor growth. Additionally, there was a clear clinical change compared to the last documented photos from 5 years prior at the treating institution. Enucleation was recommended. Pathological analysis confirmed the diagnosis of recurrent choroidal melanoma at the apex of the treated lesion, at the site of prior biopsy. Systemic surveillance was negative for metastatic disease. Current literature suggests the majority of choroidal melanoma recurrences occur within 5 years following treatment. However, this case of recurrence 10 years after brachytherapy emphasizes the importance of life-long ophthalmic care for these patients. Additionally, this case demonstrates the possibility of a rare recurrence at a prior biopsy site.


First Line CombinAtion Therapy in the Treatment of Stage II and III Hypertension (FLASH).
Background: Lowering blood pressure (BP) leads to reduced risk of stroke, myocardial infarction, and cardiovascular mortality. Single-pill combination therapies may deliver better BP control than increasing the dose of monotherapies or using more drugs separately. Objectives: The aim of the present observational study was to investigate the real-life use and the effect of first line or replacement single-pill combination therapies containing irbesartan and hydrochlorothiazide (HCTZ) on systolic BP (SBP) control rate in patients with hypertension. Methods: Overall, 780 patients with moderate or severe hypertension either untreated (289; 37%) or uncontrolled (491; 63%) with previous therapy were included in the "First Line CombinAtion Therapy in the Treatment of Stage II and III Hypertension" (FLASH) prospective Swiss national-wide cohort study. All recruited patients received single-pill antihypertensive combination therapy containing HCTZ and irbesartan. BP was measured at baseline and after 8-weeks follow-up according to guidelines. Results: Mean reductions in office systolic/diastolic BP (SBP/DBP) were 23.7 ± 13.7/11.7 ± 8.5 mmHg, with reductions of 26.9 ± 14.1/13.0 ± 8.8 mmHg or 21.8 ± 13.1/11.0 ± 8.3 mmHg when the single-pill combination of irbesartan/HCTZ was given as first line or replacement treatment, respectively (p < 0.001 for differences between first line and replacement treatment in both SBP and DBP). The guidelines-recommended goals were reached in 368 (47%), 492 (63%), and 312 (40%) patients for SBP, DBP, and SBP/DBP, respectively. The SBP control rate was higher when the combination was used as first line treatment (52 vs. 44%; p = 0.043). Overall, 145 adverse events were recorded; hypotension in 12 (1.5%) cases, hypokalaemia in 9 (1.2%), and hyperkalaemia in 3 (0.4%). Conclusions: The single-pill combination of irbesartan/HCTZ was well-tolerated and achieved substantial reductions in both systolic and diastolic BP. The SBP control rate was greater when the combination was prescribed as first line treatment as suggested by recent ESC/ESH guidelines.


Moral elevation reduces prejudice against gay men.
Disgust is linked to social evaluation. People with higher disgust sensitivity exhibit more sexual prejudice, and inducing disgust increases sexual prejudice. We tested whether inducing moral elevation, the theoretical opposite of disgust, would reduce sexual prejudice. In four studies (N = 3622), we induced elevation with inspiring videos and then measured sexual prejudice with implicit and explicit measures. Compared to control videos that elicited no particular affective state, we found that elevation reduced implicit and explicit sexual prejudice, albeit very slightly. No effect was observed when the target of social evaluation was changed to race (Black-White). Inducing amusement, another positive emotion, did not significantly affect sexual prejudice. We conclude that elevation weakly but reliably reduces prejudice towards gay men.


Onset of allergy and asthma symptoms in extra-European immigrants to Milan, Italy: possible role of environmental factors.
Allergy and asthma are typical disorders of the affluent societies. Migrants from developing to industrialized countries seem to be at increased risk of allergy and asthma development. To evaluate time of onset, spectrum of sensitization and clinical features in a population of extra-European immigrants to Milan, Italy, complaining of allergy and asthma symptoms. Data regarding 243 extra-European immigrants checked at an allergy clinic from 1994 to 2000 were collected retrospectively. The demographic data were compared with those of the extra-European immigrants living in Milan at the end of 1999. The patients were complaining of asthma (63.7%), rhinoconjunctivitis (56.7%), rhinitis alone (21%) or urticaria (3%). One hundred and eighty-seven out of 222 patients (84.3%) declared they were healthy before migrating and allergy/asthma symptoms started to appear after their arrival in Italy, namely after an average period of 4 years and 7 months. The proportion of male patients was lower than the proportion of men in the extra-European immigrant population (48% vs. 55%), suggesting that in adult immigrants allergy and asthma are more common in women than in men. Furthermore, there was an over-representation of Central-South Americans attending the clinic, which seemed to be due to a genetic predisposition to allergy/asthma development. When data were analysed for single countries, a trend towards an increased risk of allergy and asthma was found in immigrants from all Central-South American countries. A skin test positivity for at least one inhalant allergen was found in 196 out of 232 patients (81%), and the spectrum of allergic sensitization was similar to that of the Italian population living in the North of Italy. Most extra-European immigrants declared that they were healthy at home and that allergy and asthma symptoms had appeared after immigration to Milan; lifestyle and environmental factors in a western industrialized city seem indeed to facilitate allergy/asthma onset in immigrants from developing countries. Allergy/asthma risk seems to be different in different ethnic groups.


Use of alternative treatments by chronic fatigue syndrome discordant twins.
Background: Patients with chronic fatigue syndrome (CFS) have been faced with difficulties in diagnosis and lack of effective treatments. Anecdotal evidence suggests that use of alternative treatments may be common in these patients. Our primary objective was to compare the prevalence and patterns of alternative medicine use among twins who met the Centers for Disease Control and Prevention (CDC) CFS criteria to that of their non-CFS co-twins. Secondary goals were to assess how often alternative medicine use was discussed with physicians and the perceived benefit of these therapies. Methods: Sixty-three twin pairs discordant for CFS completed a survey about their use of 22 alternative therapies. Matched pair odds ratios and 95% confidence intervals were used to examine differences in the use between CFS twins and their non-CFS co-twins. Results: 91% of twins with CFS and 71% of non-CFS twins had used at least 1 alternative treatment in their lifetime. Twins with CFS were more likely to use homeopathy, mega-vitamins, herbal therapies, biofeedback, relaxation/meditation, guided imagery, massage therapy, energy healing, religious healing by others, and self-help groups than their non-CFS counterparts. A large proportion of all twins found alternative therapies helpful; however, only 42% of those with CFS and 23% of those without CFS discussed their use of alternative medicine with a physician. Conclusions: Individuals with CFS frequently used alternative medical treatments yet rarely communicated this use to their medical doctor. Future research should ascertain the usefulness of alternative practices in the management of CFS.


Clinical outcomes of bivalirudin for ischemic heart disease.
Current treatment strategies for percutaneous coronary revascularization and acute coronary syndromes incorporate thrombin inhibition with either unfractionated or fractionated heparin. The peptide bivalirudin (Hirulog) is a direct thrombin inhibitor whose pharmacological properties differ from those of heparin. We conducted a systematic overview (meta-analysis) to assess the effect of bivalirudin on 4 end points: death, myocardial infarction, major hemorrhage, and the composite of death or infarction. Six trials (5674 patients) represent the randomized, controlled bivalirudin experience, including 4603 patients undergoing elective percutaneous coronary revascularization and 1071 patients with acute coronary syndromes. ORs for the 4 clinical end points were calculated for each trial. Four trials (4973 patients) that compared bivalirudin with heparin were combined with the use of a random-effects model. In these trials, bivalirudin was associated with a significant reduction in the composite of death or infarction (OR 0.73, 95% CI 0.57 to 0.95; P=0.02) at 30 to 50 days, or 14 fewer events per 1000 patients so treated. There also was a significant reduction in major hemorrhage for the same trials (OR 0.41, 95% CI 0. 32 to 0.52; P<0.001, or 58 fewer events per 1000 patients so treated). A similar analysis combined 2 dose-ranging trials (701 patients) that compared therapeutic (activated partial thromboplastin time more than twice the control time) with subtherapeutic bivalirudin anticoagulation (activated partial thromboplastin time less than twice the control time). Bivalirudin is at least as effective as heparin, with clearly superior safety. Thus, it provides an unprecedented net clinical benefit over heparin in patients with ischemic heart disease.


[Mucocele of the appendix. Incidental sonographic discovery and laparoscopic resection].
A 76-year-old currently asymptomatic man was admitted for routine sonography of the abdomen. 15 years he had had intermittently symptomatic cholecystolithiasis. 25 years before a colon contrast showed a normal coecum but no filling of the appendix. Sonographic examination showed the known cholecystolithisasis but additionally revealed as an incidental finding a tubular-cystic structure with a thin, echogenic wall and a hypoechogenic lumen. The lesion was located in the right upper quadrant, not compressible and arising from the coecum. Computed tomography confirmed a mucocele of the appendix without ascites and no inflammatory changes, peritoneal thickening or nodules. Laparoscopic resection of the unruptured appendiceal mucocele together with cholestectomy was performed. On gross examination, the resected mucocele proved to be macroscopally an intact mass with a thin wall and full of white gelatinous material measuring 3 cm in diameter and 8 cm long. The histologic diagnosis was mucinous cystadenoma. The patient was discharged on the second postoperative day and recovered uneventfully. Because of the clear association of appendiceal cystadenoma with colorectal tumor a colonoscopy was performed which showed a normal colon. The differential diagnosis of a cystic mass in the right lower quadrant without previous appendectomy should include an appendiceal mucocele. If preoperatively there are no signs of malignancy, laparoscopic resection can be performed. In patients with histologic diagnosis of appendiceal cystadenoma: the colon should be examined to exclude synchronous colon tumors.


Cav2.1 channels control multivesicular release by relying on their distance from exocytotic Ca2+ sensors at rat cerebellar granule cells.
The concomitant release of multiple numbers of synaptic vesicles [multivesicular release (MVR)] in response to a single presynaptic action potential enhances the flexibility of synaptic transmission. However, the molecular mechanisms underlying MVR at a single CNS synapse remain unclear. Here, we show that the Cav2.1 subtype (P/Q-type) of the voltage-gated calcium channel is specifically responsible for the induction of MVR. In the rat cerebellar cortex, paired-pulse activation of granule cell (GC) ascending fibers leads not only to a facilitation of the peak amplitude (PPFamp) but also to a prolongation of the decay time (PPPdecay) of the EPSCs recorded from molecular layer interneurons. PPFamp is elicited by a transient increase in the number of released vesicles. PPPdecay is highly dependent on MVR and is caused by dual mechanisms: (1) a delayed release and (2) an extrasynaptic spillover of the GC transmitter glutamate and subsequent pooling of the glutamate among active synapses. PPPdecay was specifically suppressed by the Cav2.1 channel blocker ω-agatoxin IVA, while PPFamp responded to Cav2.2/Cav2.3 (N-type/R-type) channel blockers. The membrane-permeable slow Ca(2+) chelator EGTA-AM profoundly reduced the decay time constant (τdecay) of the second EPSC; however, it only had a negligible impact on that of the first, thereby eliminating PPPdecay. These results suggest that the distance between presynaptic Cav2.1 channels and exocytotic Ca(2+) sensors is a key determinant of MVR. By transducing presynaptic action potential firings into unique Ca(2+) signals and vesicle release profiles, Cav2.1 channels contribute to the encoding and processing of neural information.


Characterization of novel alginate-Aloe Vera raft systems for treatment of gastroesophageal reflux disease.
Raft-forming systems are designed to relieve reflux symptoms by forming a physical barrier on top of the stomach. The present study aimed to evaluate the physico-chemical properties of alginate-aloe vera raft-forming systems for the first time. To achieve this goal, aloe vera was used in the proportion of 1 and 1.5 % in raft suspensions containing 5 % alginate as the main component of gel structure. Rafts were characterized by their volume, floating behavior, thickness, swelling properties, strength, resilience, reflux resistance, and acid neutralization capacity (ANC). Results showed the effectiveness of aloe vera in forming rafts that were voluminous, buoyant with greater total floating time (TFT), and stronger than formulations with no aloe vera. Furthermore, data showed that the presence of aloe vera could improve resilience time, swelling proportions, resistance to reflux under simulant conditions of movement in the stomach, and ANC values of rafts. Rafts were further characterized by oscillatory strain sweep test, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Evaluation of the mechanical properties of rafts displayed a viscoelastic behavior of gels corresponding to the internal cross-linked structure of rafts. This study demonstrated that designing of alginate-aloe vera rafts can be suitable for the treatment of gastro-esophageal reflux disorders.


Pitch-side Acute Severe Pain Management Decisions in European Elite Football.
This is the first study on acute severe pain management involving sport and exercise medicine Doctors who are leaders in football medicine in their respective countries. An online survey was designed describing the management of acute severe pain in this expert cohort. The survey captured participant sex, age, years working in sports medicine, core specialty and use of clinical practice guidelines (CPGs). Finally, three clinical vignettes exploring the management of acute pain were presented. Forty-four senior team doctors across 55 European countries completed the survey. There were no consistent guidelines proposed, with 33 (75%) participants indicating they did not use any. Methoxyflurane was proposed by 14 (32%) and 13 (30%) participants for female anterior cruciate ligament rupture and male ankle fracture, respectively. Strong opioids were not used in 17 (39%) and 6 (14%) participants regarding female cruciate injuries and male fractures, respectively. Despite 75% of participants having paediatric life support training, eight (18%) participants expressed uncertainty administering medications in this population, and 15 (34%) would avoid using strong opioids altogether. There is a tendency to undertreat pain and avoid strong opioids for reasons including lack of monitoring equipment, anti-doping concerns and lack of comfort treating paediatric patients with opioids.


SET protein modulates H4 histone methylation status and regulates miR-137 level in oral squamous cell carcinoma.
Aim: Histone acetylation and methylation control gene expression. We investigated the impact of SET knockdown on histone methylation status and the consequences for the miRNAs levels in oral squamous cell carcinoma (OSCC). Methods: OSCC cells with and without SET knockdown were analyzed by quantitative real-time PCR to determine miRNA levels, and by immunoreactions to histone modifications. Results: The knockdown of SET increased the levels of histone H4K20me2 and miR-137. Still, SET protein binds to the miR-137 promoter region. The transfection of miR-137 mimic reduced the KI67 and Rb proteins and proliferation of OSCC cells. Conclusion: Our results show for the first time a relationship between SET and histone methylation associated with the control of miRNA expression and KI67 and Rb as targets of miR-137 in OSCC.


Expression of multidrug resistance protein in metastatic colorectal carcinomas.
To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.


Clinical applications of fucoidan in translational medicine for adjuvant cancer therapy.
The chemical composition of fucoidan, a kind of sulfated polysaccharide mainly derived from brown seaweed, includes a substantial percentage of L-fucose. Fucoidan has various biological and pharmacological activities, such as anti-cancer/anti-tumor, anti-proliferation, anti-inflammatory and immune-modulatory functions, and fucoidan-related dietary supplements and nutraceuticals have recently drawn considerable attention. In this review, we aim to provide a current view of different aspects of fucoidan biological activity, with a focus on the anti-cancer regulatory effects of fucoidan on growth signaling mechanisms. First, we discuss historical aspects of fucoidan and fucoidan products, as well as the anti-cancer effects of fucoidan on various cancer cells. Second, we discuss fucoidan's biological activities and induction of cell death in cancer cells, including multiple mechanisms and signal transduction pathways related to its anti-cancer effects. Next, we focus on fucoidan and fucoidan-derived products that have been marketed as dietary supplements or nutraceuticals for cancer, including anti-cancer effects of fucoidan when combined as an adjuvant with clinical drugs. Finally, case studies of fucoidan in complementary therapy and as an alternative medicine in animal and mouse models and human clinical trials to alleviate side effects of anti-cancer chemotherapy are discussed. Combining fucoidan with clinical therapeutic agents in the treatment of cancer patients, dissecting the related signal transduction pathways and investigating their dynamic interactions may reveal potential molecular targets in cancer prevention, therapies and key obstacles in the current development of anti-cancer strategies.


[Occurrence of preterm and term low birth weight deliveries and presence of the Sydney crease].
To determine whether simian and Sydney creases are associated to preterm delivery or to term low birth weight. We performed a cross-sectional study of 490 live newborns without apparent malformations from the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). Patients were categorized in three groups: group I: 175 infants with preterm delivery; group II: 140 term low birth weight infants; group III: 175 at term newborns with adequate weight for gestational age. On all groups, perinatal history was registered and palm creases were studied by direct inspection and classified as normal, simian crease (single palmar flexion crease) or Sydney crease (continuation of the proximal palmar crease until the ulnar border of the palm). We used the odds ratio as an association measurement, with 95% confidence intervals. The simian crease frequency did not show significant differences between groups. Sydney crease frequencies on groups I, II and lll were 29.7, 34.2 and 18.2%, respectively (p = 0.0037). Sydney crease presence was associated with near to two-fold frequency to preterm birth (OR: 1.89, 95% CI: 1.11-3.23) and more than double with low birth weight (OR: 2.33, 95% Cl: 1.07-5.23). Sydney crease was associated with occurrence of the preterm and term low birth weight deliveries.


Cytokine-induced inflammation in the central nervous system revisited.
Cytokines play an essential role as mediators of the immune response. They usually function as part of a network of interactive signals that either activate, enhance, or inhibit the ensuing reaction. An important contribution of this cytokine cascade is the induction of an inflammatory response that recruits and activates subsets of leukocytes that function as effector cells in the response to the sensitizing antigen. Proinflammatory cytokines activate endothelial cells (EC) to express adhesion molecules and induce the release of members of the chemokine family, thus focusing and directing the inflammatory response to sites of antigen recognition. However, the vasculature of the central nervous system (CNS) is highly specialized and restricts the access of components of the immune system to the CNS compartment. In this review, we address the question as to whether endothelial cells in the CNS respond differently to specific cytokines known to induce either a proinflammatory effect or a regulatory effect in systemic vascular beds.


Selenium concentrations and enzyme activities of glutathione metabolism in wild long-tailed ducks and common eiders.
The relationships of selenium (Se) concentrations in whole blood with plasma activities of total glutathione peroxidase, Se-dependent glutathione peroxidase, and glutathione reductase were studied in long-tailed ducks (Clangula hyemalis) and common eiders (Somateria mollissima) sampled along the Beaufort Sea coast of Alaska, USA. Blood Se concentrations were >8 µg/g wet weight in both species. Linear regression revealed that the activities of total and Se-dependent glutathione peroxidase were significantly related to Se concentrations only in long-tailed ducks, raising the possibility that these birds were experiencing early oxidative stress.


Cyclooxygenase-2 expression in non-Hodgkin's lymphomas.
Cyclooxygenase 2 (Cox-2) is a key enzyme in prostaglandin synthesis and it has an important role in the pathogenesis of various malignancies. Cox-2 has been studied in solid tumors; however, studies about the role of Cox-2 in non-Hodgkin's lymphomas (NHL) are limited. The aim of this study is to determine the importance of Cox-2 expression in lymphomas. To this end, Cox-2 expression was determined in 177 cases with NHL. In histological terms, 60 cases (33%) had low grade and 117 (67%) had aggressive lymphoma. Ninety-nine cases were found to be positive for Cox-2 (56%); Cox-2 score was between 50 and 100, 101 and 200 and over 200 in 38, 46 and 15 cases, respectively. There was an important association between aggressive histology and Cox-2 expression: Cox-2 was negative in about half of the cases with indolent morphology, while two thirds of the Cox-2 positive cases had aggressive histology (p = 0.036). There was no significant association between Cox-2 expression and clinical-laboratory parameters. Although the overall survival times were longer in cases with lower or no Cox-2 expression as compared with higher Cox-2 expression, the difference was not significant. In conclusion Cox-2 expression is seen about 60% of the cases with NHL and is associated with aggressive morphology.


Improvement of human myeloma stem cell growth in a liquid culture system supplemented with phytohemagglutinin.
A highly efficient cloning system for in vitro myeloma colony growth could be valuable for screening antineoplastic agents in resistant patients and for testing the effects of purging methods in the context of autologous bone marrow transplantation. In this paper we report the results of experiments intended to improve the myeloma cloning system in plasma clot originally described by Ludwig et al. We tested the effects of the addition of phytohemagglutinin (PHA), coupled with a transformation of the original plasma clot method into a liquid culture system. A statistically higher number of myeloma colonies was observed in the liquid system in the presence of PHA (20 cases, median 84.5 vs. 9.5; p = 0.005), whereas a single variant (either PHA alone or liquid system alone) did not determine any significant growth variation. The increase in the cloning efficiency was evident even in the cases characterized by low bone marrow plasma cell infiltration, suggesting that this method is suitable for the described purposes.


Rapid Detection of SARS-CoV-2 Antigens and Antibodies Using OFET Biosensors Based on a Soft and Stretchable Semiconducting Polymer.
In the midst of the COVID-19 pandemic, adaptive solutions are needed to allow us to make fast decisions and take effective sanitation measures, e.g., the fast screening of large groups (employees, passengers, pupils, etc.). Although being reliable, most of the existing SARS-CoV-2 detection methods cannot be integrated into garments to be used on demand. Here, we report an organic field-effect transistor (OFET)-based biosensing device detecting of both SARS-CoV-2 antigens and anti-SARS-CoV-2 antibodies in less than 20 min. The biosensor was produced by functionalizing an intrinsically stretchable and semiconducting triblock copolymer (TBC) film either with the anti-S1 protein antibodies (S1 Abs) or receptor-binding domain (RBD) of the S1 protein, targeting CoV-2-specific RBDs and anti-S1 Abs, respectively. The obtained sensing platform is easy to realize due to the straightforward fabrication of the TBC film and the utilization of the reliable physical adsorption technique for the molecular immobilization. The device demonstrates a high sensitivity of about 19%/dec and a limit of detection (LOD) of 0.36 fg/mL for anti-SARS-Cov-2 antibodies and, at the same time, a sensitivity of 32%/dec and a LOD of 76.61 pg/mL for the virus antigen detection. The TBC used as active layer is soft, has a low modulus of 24 MPa, and can be stretched up to 90% with no crack formation of the film. The TBC is compatible with roll-to-roll printing, potentially enabling the fabrication of low-cost wearable or on-skin diagnostic platforms aiming at point-of-care concepts.


Sensing senses: tactile feedback for the prevention of decubitus ulcers.
Decubitus ulcers, also known as pressure sores, is a major problem in health care, in particular for patients with spinal cord injuries. These patients cannot feel the discomfort that would urge healthy people to change their posture. We describe a system that uses a sensor mat to detect problematic postures and provides tactile feedback to the user. The results of our preliminary study with healthy subjects show that the tactile feedback is a viable option to spoken feedback. We envision the system being used for rehabilitation games, but also for everyday Decubitus ulcers prevention.


Single-port robot-assisted radical prostatectomy with the da Vinci SP system: A single surgeon's experience.
To report an initial single-surgeon experience with single-port robot-assisted radical prostatectomy (SP-RARP) using the da Vinci SP surgical system (Intuitive Surgical, USA). Between December 2018 and October 2019, a single surgeon performed SP-RARP in 20 patients with prostate cancer. SP-RARP was performed using the conventional approach through an umbilical port with a GelPOINT access system (Applied Medical, USA) and an additional assist port. During surgery, the camera was placed in the 6- or 12-o'clock position, and a traction arm was placed in the counterpart position for upward or downward traction. Clinicopathologic data, perioperative data, and short-term surgical outcomes were analyzed. Of 20 patients, 45% of patients had pT3 or greater disease and 45% had Gleason grade 4 to 5, respectively. In 11 patients that underwent lymph node dissection, the median number of lymph nodes removed was 19 (interquartile range [IQR], 14-22). Median operative time was 245 minutes (IQR, 200-255), and median console time was 190 minutes (IQR, 165-210). Median blood loss was 200 mL (IQR, 150-300 mL), and there were no intraoperative complications or open conversion. In 10 patients with a follow-up period longer than 3 months, one patient experienced biochemical recurrence, and all patients required 0 to 1 pads per day. Of seven patients that were potent before surgery, four recovered erectile function sufficient for intercourse. Our report shows the safety and feasibility of SP-RARP, and that the associated surgical outcomes with short-term follow-up are satisfactory.


The angiographic evaluation of human renal allotransplants. Functional graft deterioration and hypertension.
The renal arteriogram is a highly reliable test in the differential diagnosis of early transplant anuria, graft rejection, and hypertension. The reliability of the renal arteriogram was 97.8% in either substantiating or disproving the presence of a suspected episode of graft rejection or renal artery stenosis. The earliest signs of acute humoral and acute rejection were a prolongation of arterial clearance time, diffuse edema with enlargement of the kidney, and progressive deterioration of the nephrogram. Renal artery stenosis may be a sharply localized septum or an elongated narrowing at or distal to the actual site of anastomosis. This was seen primarily in patients' arteriograms more than 60 days after transplantation, and it is important because it is a surgically correctable cause of hypertension.


How to weight chronic diseases in multimorbidity indices? Development of a new method on the basis of individual data from five population-based studies.
In multimorbidity indices, chronic conditions are often weighted according to their severity or their impact on different outcomes. These weights are mostly developed on the basis of only one study population by using very specific study participants, such as hospital patients. To overcome the limited validity of the indices, mean weights across five population-based studies were calculated according to the impact of diseases on self-reported health status. Individual data was provided from the National Health Interview and Examination Survey (n=1,010), Dortmund Health Study (n=281), Memory and Morbidity in Augsburg Elderly Study (n=385), Survey of Health, Aging and Retirement in Europe Study (n=1,278), and Study of Health in Pomerania Study (n=962). By using logistic regression analysis, odds ratios (ORs) were calculated for reporting a fair or poor health status resulting from one of 10 different chronic conditions compared with a reference group without the specific disease, controlling for age and sex. If the results were homogenous across studies (I(2)<40%), significant pooled ORs were considered valid weights for a multimorbidity index. Myocardial infarction has the highest impact on self-reported health status across studies with a pooled OR of 3.9, followed by chronic obstructive pulmonary disease (pooled OR: 3.1). A medium impact was observed for arthrosis, asthma, diabetes mellitus, and osteoporosis. This method provided valid weights for seven chronic conditions.


Maximum likelihood optimal and robust Support Vector Regression with lncosh loss function.
In this paper, a novel and continuously differentiable convex loss function based on natural logarithm of hyperbolic cosine function, namely lncosh loss, is introduced to obtain Support Vector Regression (SVR) models which are optimal in the maximum likelihood sense for the hyper-secant error distributions. Most of the current regression models assume that the distribution of error is Gaussian, which corresponds to the squared loss function and has helpful analytical properties such as easy computation and analysis. However, in many real world applications, most observations are subject to unknown noise distributions, so the Gaussian distribution may not be a useful choice. The developed SVR model with the parameterized lncosh loss provides a possibility of learning a loss function leading to a regression model which is maximum likelihood optimal for a specific input-output data. The SVR models obtained with different parameter choices of lncosh loss with ε-insensitiveness feature, possess most of the desirable characteristics of well-known loss functions such as Vapnik's loss, the Squared loss, and Huber's loss function as special cases. In other words, it is observed in the extensive simulations that the mentioned lncosh loss function is entirely controlled by a single adjustable λ parameter and as a result, it allows switching between different losses depending on the choice of λ. The effectiveness and feasibility of lncosh loss function are validated through a number of synthetic and real world benchmark data sets for various types of additive noise distributions.


[When asthma starts].
Asthma is a frequent chronic inflammatory disease which is often mistaken for simple bronchitis. The diagnosis is based on the association of symptoms and excessive airway calibre variability. When symptoms are present more than once a week, it is recommended to give low dose inhaled corticoids as a maintenance treatment together with, as needed, rapid acting beta2 agonist. In addition it is crucial to provide the patient with an education on the disease to reinforce adherence to the treatment.