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  • When applied to dynamical systems, both classical and quantum, time periodic modulations can produce complex non-equilibrium states which are often termed "chaotic." Being well understood within the unitary Hamiltonian framework, this phenomenon is less explored in open quantum systems. Here, we consider quantum chaotic states emerging in a leaky cavity when the intracavity photonic mode is coherently pumped with the pumping intensity varying periodically in time. We show that a single spin when placed inside the cavity and coupled to the mode can moderate transitions between regular and chaotic regimes-that are identified by using quantum Lyapunov exponents or features of photon emission statistics-and thus can be used to control the degree of chaos.The peroxidase-oxidase (PO) reaction involves the oxidation of reduced nicotinamide adenine dinucleotide by molecular oxygen. When both reactants are supplied continuously to a reaction mixture containing the enzyme and a phenolic compound, the reaction will exhibit oscillatory behavior. In fact, the reaction exhibits a zoo of dynamical behaviors ranging from simple periodic oscillations to period-doubled and mixed mode oscillations to quasiperiodicity and chaos. The routes to chaos involve period-doubling, period-adding, and torus bifurcations. The dynamic behaviors in the experimental system can be simulated by detailed semiquantitative models. https://www.selleckchem.com/products/MLN-2238.html Previous models of the reaction have omitted the phenolic compound from the reaction scheme. In the current paper, we present new experimental results with the oscillating PO reaction that add to our understanding of its rich dynamics, and we describe a new variant of a previous model, which includes the chemistry of the phenol in the reaction mechanism. This new model can simulate most of the experimental behaviors of the experimental system including the new observations presented here. For example, the model reproduces the two main routes to chaos observed in experiments (i) a period-doubling scenario, which takes place at low pH, and a period-adding scenario involving mixed mode oscillations (MMOs), which occurs at high pH. Our simulations suggest alternative explanations for the pH-sensitivity of the dynamics. We show that the MMO domains are separated by narrow parameter regions of chaotic behavior or quasiperiodicity. These regions start as tongues of secondary quasiperiodicity and develop into strange attractors through torus breakdown.The study of epidemics spreading with community structure has become a hot topic. The classic SIR epidemic model does not distinguish between dead and recovered individuals. It is inappropriate to classify dead individuals as recovered individuals because the real-world epidemic spread processes show different recovery rates and death rates in different communities. In the present work, a SIRD epidemic model with different recovery rates is proposed. We pay more attention to the changes in the number of dead individuals. The basic reproductive number is obtained. The stationary solutions of a disease-free state and an endemic state are given. We show that quarantining communities can decrease the basic reproductive number, and the total number of dead individuals decreases in a disease-free steady state with an increase in the number of quarantined communities. The most effective quarantining strategy is to preferentially quarantine some communities/cities with a greater population size and a fraction of initially infected individuals. Furthermore, we show that the population flows from a low recovery rate and high population density community/city/country to some high recovery rate and low population density communities/cities/countries, which helps to reduce the total number of dead individuals and prevent the prevalence of epidemics. The numerical simulations on the real-world network and the synthetic network further support our conclusions.How long-term cooperation is maintained in a society is an important and interesting question. The evolutionary game theory is often used as the basic framework to study this topic. The social status of game participants has an important influence on individual decision-making. Enlightened by this thought, we present a classification imitation model where the mechanisms of the celebrity effect and incomplete egoism are presented. The celebrity effect is reflected in each strategy update process to probe how individual decision-making is dynamically adjusted by comparing the social status of both parties in the game. The incomplete egoism refers to the irrational imitation of celebrities while self-interest is ignored. With this model, the group cooperation decision-making mechanism led by celebrities is revealed. Large-scale Monte Carlo simulations show that the incomplete egoism of individuals cannot stimulate cooperation but guarantee the stable existence of cooperation. Furthermore, the scale-free and community structure of the network enables cooperation to spread widely and maintains long-term survival. Our conclusion might provide practically new insight into the understanding and controlling of cooperation in the complex social systems.Dynamical systems running on the top of complex networks have been extensively investigated for decades. But this topic still remains among the most relevant issues in complex network theory due to its range of applicability. The contact process (CP) and the susceptible-infected-susceptible (SIS) model are used quite often to describe epidemic dynamics. Despite their simplicity, these models are robust to predict the kernel of real situations. In this work, we review concisely both processes that are well-known and very applied examples of models that exhibit absorbing-state phase transitions. In the epidemic scenario, individuals can be infected or susceptible. A phase transition between a disease-free (absorbing) state and an active stationary phase (where a fraction of the population is infected) are separated by an epidemic threshold. For the SIS model, the central issue is to determine this epidemic threshold on heterogeneous networks. For the CP model, the main interest is to relate critical exponents with statistical properties of the network.
    When applied to dynamical systems, both classical and quantum, time periodic modulations can produce complex non-equilibrium states which are often termed "chaotic." Being well understood within the unitary Hamiltonian framework, this phenomenon is less explored in open quantum systems. Here, we consider quantum chaotic states emerging in a leaky cavity when the intracavity photonic mode is coherently pumped with the pumping intensity varying periodically in time. We show that a single spin when placed inside the cavity and coupled to the mode can moderate transitions between regular and chaotic regimes-that are identified by using quantum Lyapunov exponents or features of photon emission statistics-and thus can be used to control the degree of chaos.The peroxidase-oxidase (PO) reaction involves the oxidation of reduced nicotinamide adenine dinucleotide by molecular oxygen. When both reactants are supplied continuously to a reaction mixture containing the enzyme and a phenolic compound, the reaction will exhibit oscillatory behavior. In fact, the reaction exhibits a zoo of dynamical behaviors ranging from simple periodic oscillations to period-doubled and mixed mode oscillations to quasiperiodicity and chaos. The routes to chaos involve period-doubling, period-adding, and torus bifurcations. The dynamic behaviors in the experimental system can be simulated by detailed semiquantitative models. https://www.selleckchem.com/products/MLN-2238.html Previous models of the reaction have omitted the phenolic compound from the reaction scheme. In the current paper, we present new experimental results with the oscillating PO reaction that add to our understanding of its rich dynamics, and we describe a new variant of a previous model, which includes the chemistry of the phenol in the reaction mechanism. This new model can simulate most of the experimental behaviors of the experimental system including the new observations presented here. For example, the model reproduces the two main routes to chaos observed in experiments (i) a period-doubling scenario, which takes place at low pH, and a period-adding scenario involving mixed mode oscillations (MMOs), which occurs at high pH. Our simulations suggest alternative explanations for the pH-sensitivity of the dynamics. We show that the MMO domains are separated by narrow parameter regions of chaotic behavior or quasiperiodicity. These regions start as tongues of secondary quasiperiodicity and develop into strange attractors through torus breakdown.The study of epidemics spreading with community structure has become a hot topic. The classic SIR epidemic model does not distinguish between dead and recovered individuals. It is inappropriate to classify dead individuals as recovered individuals because the real-world epidemic spread processes show different recovery rates and death rates in different communities. In the present work, a SIRD epidemic model with different recovery rates is proposed. We pay more attention to the changes in the number of dead individuals. The basic reproductive number is obtained. The stationary solutions of a disease-free state and an endemic state are given. We show that quarantining communities can decrease the basic reproductive number, and the total number of dead individuals decreases in a disease-free steady state with an increase in the number of quarantined communities. The most effective quarantining strategy is to preferentially quarantine some communities/cities with a greater population size and a fraction of initially infected individuals. Furthermore, we show that the population flows from a low recovery rate and high population density community/city/country to some high recovery rate and low population density communities/cities/countries, which helps to reduce the total number of dead individuals and prevent the prevalence of epidemics. The numerical simulations on the real-world network and the synthetic network further support our conclusions.How long-term cooperation is maintained in a society is an important and interesting question. The evolutionary game theory is often used as the basic framework to study this topic. The social status of game participants has an important influence on individual decision-making. Enlightened by this thought, we present a classification imitation model where the mechanisms of the celebrity effect and incomplete egoism are presented. The celebrity effect is reflected in each strategy update process to probe how individual decision-making is dynamically adjusted by comparing the social status of both parties in the game. The incomplete egoism refers to the irrational imitation of celebrities while self-interest is ignored. With this model, the group cooperation decision-making mechanism led by celebrities is revealed. Large-scale Monte Carlo simulations show that the incomplete egoism of individuals cannot stimulate cooperation but guarantee the stable existence of cooperation. Furthermore, the scale-free and community structure of the network enables cooperation to spread widely and maintains long-term survival. Our conclusion might provide practically new insight into the understanding and controlling of cooperation in the complex social systems.Dynamical systems running on the top of complex networks have been extensively investigated for decades. But this topic still remains among the most relevant issues in complex network theory due to its range of applicability. The contact process (CP) and the susceptible-infected-susceptible (SIS) model are used quite often to describe epidemic dynamics. Despite their simplicity, these models are robust to predict the kernel of real situations. In this work, we review concisely both processes that are well-known and very applied examples of models that exhibit absorbing-state phase transitions. In the epidemic scenario, individuals can be infected or susceptible. A phase transition between a disease-free (absorbing) state and an active stationary phase (where a fraction of the population is infected) are separated by an epidemic threshold. For the SIS model, the central issue is to determine this epidemic threshold on heterogeneous networks. For the CP model, the main interest is to relate critical exponents with statistical properties of the network.
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  • Premature or primary ovarian insufficiency (POI) affects approximately 1% of women and can be due to a variety of causes. Genetic causes include syndromic and non-syndromic POI. There are several promising candidate genes for whom a clear Mendelian association with non-syndromic POI has not yet been conclusively established, including GDF9. GDF9 is an oocyte-secreted factor and is part of the TGF-beta superfamily of morphogens. It has an important role in follicular development and granulosa cell maturation. We report the case of two siblings with primary ovarian insufficiency (POI) and a homozygous truncating variant in GDF9 (c.604C>T; p.(Gln202*). This report helps establish a clear gene-disease association between GDF9 and POI and argues for routine evaluation for GDF9 variants in patients undergoing genomic investigation for POI.
    To characterize national oocyte donation practice patterns from the perspective of individual donors rather than of recipients.

    Retrospective cohort including all donor oocyte retrievals and transfers reported to SARTCORS in 2016 and 2017 in the USA. https://www.selleckchem.com/products/bi-1015550.html Primary outcomes include characteristics of oocyte donors and of donor oocyte cycles. Secondary outcomes include overall pregnancy rates, elective single embryo transfer (eSET) rates, and perinatal outcomes among donor oocyte recipient transfers.

    During the study period, 49,193 donor oocyte retrievals were performed, of which the largest proportion were in the Western US. For all reported retrievals, there were 17,099 unique donors, each of whom underwent an average of 2.4 retrievals (range 1-22). Average donor age was 26.3 years (range 18-48). On average, 24.6 oocytes (SD 12.4) were retrieved each cycle, ranging from 0 to 102. Among 37,657 donor oocyte recipient transfers, 20,159 (53.5%) involved eSET, and 17,725 (47.1%) resulted in live birth. Miscarriagee donor recipient eSET rates.
    To assess perceived deficiencies of reproductive endocrinology and infertility (REI) fellow education due to changes in care secondary to COVID-19.

    This is a cross-sectional study performed in an academic setting. A survey was generated and administered to REI fellows and attendings practicing in programs across the United States. Descriptive statistics were used to quantify results regarding clinical volume, academic responsibilities, clinical safety, and fellowship education.

    The survey response rate was 23%. Eighty-four percent of respondents self-identified as fellows, and 16% identified as program directors or other REI academic instructors. Overall, the survey responses confirmed that the COVID-19 pandemic tremendously affected clinical volume, with 91% of participants reporting their clinical volume decreased by at least half. Although 67% of attendings believed that the changes related to COVID-19 have or will have significantly affected the clinical skills of fellows, 66% of fellows did not believe that their clinical training had been significantly impacted. Sixty-seven percent of fellows and 78% of attendings do not believe that changes related to COVID-19 willaffect the ability of fellows to practice independently.

    Even though most attendings surveyed believed that the changes related to COVID-19 would affect the clinical skills of fellows, the cessation of clinical and research activities was short-lived, likely tempering the overall effect on clinical training. Overall, most respondents did not believe that the pandemic significantly affected fellow education.
    Even though most attendings surveyed believed that the changes related to COVID-19 would affect the clinical skills of fellows, the cessation of clinical and research activities was short-lived, likely tempering the overall effect on clinical training. Overall, most respondents did not believe that the pandemic significantly affected fellow education.We examined the morphology of fertilized egg and ultrastructures of fertilized egg envelopes of dwarf rainbowfish (Melanotaenia praecox) belong to Melanotaeniidae using light and electron microscopes. The fertilized eggs were spherical with adhesive filament, transparent, demersal, and had a narrow perivitelline space and small oil droplets. The size of fertilized egg was 1.02 ± 0.18 mm (n = 30), and there were two kinds of adhesive filament on the fertilized eggs. The long and thick (diameter 12.22 ± 0.52 μm, n = 20) adhesive filaments were only at the area of animal pole, and short and thin (diameter 1.99 ± 0.23 μm, n = 20) adhesive filaments were around the long filaments. A micropyle was conical shaped with adhesive filament and located near the animal pole of egg. The outer surface of fertilized egg was rough side. Also, the total thickness of the fertilized egg envelope was about 7.46 ± 0.41 μm (n = 20), the fertilized egg envelope consisted of two layers, an inner lamellae layer and an outer layer with high electron-density. And the inner layer was 8 layers. Collectively, these morphological characteristics and adhesive property of fertilized egg with adhesive filaments, and ultrastructures of micropyle, outer surface, and section of fertilized egg envelope are showed species specificity.
    The aim of this study was to examine the survival effect of adjuvant therapy in stage II-III endometrial cancer based on peritoneal cytology results.

    The National Cancer Institute'sSurveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II-III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results.

    Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p<0.05). In a propensity score-weighted model, malignant peritoneal cytology was associated with increased all-cause mortality compared with negative peritoneal cytology (hazard ratio 1.35, 95% confidence interval 1.23-1.48). Adjuvant therapy types varied based on histology and peritoneal cytology results.
    Premature or primary ovarian insufficiency (POI) affects approximately 1% of women and can be due to a variety of causes. Genetic causes include syndromic and non-syndromic POI. There are several promising candidate genes for whom a clear Mendelian association with non-syndromic POI has not yet been conclusively established, including GDF9. GDF9 is an oocyte-secreted factor and is part of the TGF-beta superfamily of morphogens. It has an important role in follicular development and granulosa cell maturation. We report the case of two siblings with primary ovarian insufficiency (POI) and a homozygous truncating variant in GDF9 (c.604C>T; p.(Gln202*). This report helps establish a clear gene-disease association between GDF9 and POI and argues for routine evaluation for GDF9 variants in patients undergoing genomic investigation for POI. To characterize national oocyte donation practice patterns from the perspective of individual donors rather than of recipients. Retrospective cohort including all donor oocyte retrievals and transfers reported to SARTCORS in 2016 and 2017 in the USA. https://www.selleckchem.com/products/bi-1015550.html Primary outcomes include characteristics of oocyte donors and of donor oocyte cycles. Secondary outcomes include overall pregnancy rates, elective single embryo transfer (eSET) rates, and perinatal outcomes among donor oocyte recipient transfers. During the study period, 49,193 donor oocyte retrievals were performed, of which the largest proportion were in the Western US. For all reported retrievals, there were 17,099 unique donors, each of whom underwent an average of 2.4 retrievals (range 1-22). Average donor age was 26.3 years (range 18-48). On average, 24.6 oocytes (SD 12.4) were retrieved each cycle, ranging from 0 to 102. Among 37,657 donor oocyte recipient transfers, 20,159 (53.5%) involved eSET, and 17,725 (47.1%) resulted in live birth. Miscarriagee donor recipient eSET rates. To assess perceived deficiencies of reproductive endocrinology and infertility (REI) fellow education due to changes in care secondary to COVID-19. This is a cross-sectional study performed in an academic setting. A survey was generated and administered to REI fellows and attendings practicing in programs across the United States. Descriptive statistics were used to quantify results regarding clinical volume, academic responsibilities, clinical safety, and fellowship education. The survey response rate was 23%. Eighty-four percent of respondents self-identified as fellows, and 16% identified as program directors or other REI academic instructors. Overall, the survey responses confirmed that the COVID-19 pandemic tremendously affected clinical volume, with 91% of participants reporting their clinical volume decreased by at least half. Although 67% of attendings believed that the changes related to COVID-19 have or will have significantly affected the clinical skills of fellows, 66% of fellows did not believe that their clinical training had been significantly impacted. Sixty-seven percent of fellows and 78% of attendings do not believe that changes related to COVID-19 willaffect the ability of fellows to practice independently. Even though most attendings surveyed believed that the changes related to COVID-19 would affect the clinical skills of fellows, the cessation of clinical and research activities was short-lived, likely tempering the overall effect on clinical training. Overall, most respondents did not believe that the pandemic significantly affected fellow education. Even though most attendings surveyed believed that the changes related to COVID-19 would affect the clinical skills of fellows, the cessation of clinical and research activities was short-lived, likely tempering the overall effect on clinical training. Overall, most respondents did not believe that the pandemic significantly affected fellow education.We examined the morphology of fertilized egg and ultrastructures of fertilized egg envelopes of dwarf rainbowfish (Melanotaenia praecox) belong to Melanotaeniidae using light and electron microscopes. The fertilized eggs were spherical with adhesive filament, transparent, demersal, and had a narrow perivitelline space and small oil droplets. The size of fertilized egg was 1.02 ± 0.18 mm (n = 30), and there were two kinds of adhesive filament on the fertilized eggs. The long and thick (diameter 12.22 ± 0.52 μm, n = 20) adhesive filaments were only at the area of animal pole, and short and thin (diameter 1.99 ± 0.23 μm, n = 20) adhesive filaments were around the long filaments. A micropyle was conical shaped with adhesive filament and located near the animal pole of egg. The outer surface of fertilized egg was rough side. Also, the total thickness of the fertilized egg envelope was about 7.46 ± 0.41 μm (n = 20), the fertilized egg envelope consisted of two layers, an inner lamellae layer and an outer layer with high electron-density. And the inner layer was 8 layers. Collectively, these morphological characteristics and adhesive property of fertilized egg with adhesive filaments, and ultrastructures of micropyle, outer surface, and section of fertilized egg envelope are showed species specificity. The aim of this study was to examine the survival effect of adjuvant therapy in stage II-III endometrial cancer based on peritoneal cytology results. The National Cancer Institute'sSurveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II-III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results. Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p<0.05). In a propensity score-weighted model, malignant peritoneal cytology was associated with increased all-cause mortality compared with negative peritoneal cytology (hazard ratio 1.35, 95% confidence interval 1.23-1.48). Adjuvant therapy types varied based on histology and peritoneal cytology results.
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  • Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.Mental imagery of movement is a potentially valuable rehabilitation task, but its therapeutic efficacy may depend on the specific cognitive strategy employed. Individuals use two main strategies to perform the hand mental rotation task (HMRT), which involves determining whether a visual image depicts a left or right hand. One is the motor imagery (MI) strategy, which involves mentally simulating one's own hand movements. In this case, task performance as measured by response time (RT) is subject to a medial-lateral effect wherein the RT is reduced when the fingertips are directed medially, presumably as the actual motion would be easier. The other strategy is to employ visual imagery (VI), which involves mentally rotating the picture and is not subject to this medial-lateral effect. The rehabilitative benefits of the HMRT are thought to depend on the MI strategy (mental practice), so it is essential to examine the effects of individual factors such as age, image perspective (e.g., palm or **** of the hand), and innate ability (as indicated by baseline RT) on the strategy adopted. When presented with pictures of the palm, all subjects in the current study used the MI strategy, regardless of age and ability. In contrast, when subjects were presented with pictures of the **** of the hand, the VI strategy predominated among the young age group regardless of performance, while the strategy used by middle-age and elderly groups depended on performance ability. In the middle-age and elderly groups, the VI approach predominated in those with high performance skill, whereas the MI strategy predominated among those with low performance skill. Thus, higher-skill middle-aged and elderly individuals may not necessarily form a motion image during the HMRT, potentially limiting rehabilitation efficacy.Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation (rTMS). While recording the electroencephalogram (EEG), we applied single-pulse TMS (sp-TMS) and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. https://www.selleckchem.com/products/gdc-0084.html We assessed local and global modulation of phase dynamics using the phase-locking factor (PLF). sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies (natural frequencies) enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony.Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson's disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed - one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the "start" and the "end" EPs respectively.
    Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.Mental imagery of movement is a potentially valuable rehabilitation task, but its therapeutic efficacy may depend on the specific cognitive strategy employed. Individuals use two main strategies to perform the hand mental rotation task (HMRT), which involves determining whether a visual image depicts a left or right hand. One is the motor imagery (MI) strategy, which involves mentally simulating one's own hand movements. In this case, task performance as measured by response time (RT) is subject to a medial-lateral effect wherein the RT is reduced when the fingertips are directed medially, presumably as the actual motion would be easier. The other strategy is to employ visual imagery (VI), which involves mentally rotating the picture and is not subject to this medial-lateral effect. The rehabilitative benefits of the HMRT are thought to depend on the MI strategy (mental practice), so it is essential to examine the effects of individual factors such as age, image perspective (e.g., palm or back of the hand), and innate ability (as indicated by baseline RT) on the strategy adopted. When presented with pictures of the palm, all subjects in the current study used the MI strategy, regardless of age and ability. In contrast, when subjects were presented with pictures of the back of the hand, the VI strategy predominated among the young age group regardless of performance, while the strategy used by middle-age and elderly groups depended on performance ability. In the middle-age and elderly groups, the VI approach predominated in those with high performance skill, whereas the MI strategy predominated among those with low performance skill. Thus, higher-skill middle-aged and elderly individuals may not necessarily form a motion image during the HMRT, potentially limiting rehabilitation efficacy.Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation (rTMS). While recording the electroencephalogram (EEG), we applied single-pulse TMS (sp-TMS) and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. https://www.selleckchem.com/products/gdc-0084.html We assessed local and global modulation of phase dynamics using the phase-locking factor (PLF). sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies (natural frequencies) enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony.Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson's disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed - one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the "start" and the "end" EPs respectively.
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  • Gray mold disease caused by Botrytis cinerea is a devastating disease that leads to serious financial loss. In this study, the entomopathogenic fungus Metarhizium anisopliae that acts against the gray mold pathogen B. cinerea was evaluated. M. anisopliae produced a significant inhibition zone in front of the B. https://www.selleckchem.com/products/emd-1214063.html cinerea colony in the dual culture test. In addition, volatile organic compounds generated by M. anisopliae were shown to have an inhibitory effect on B. cinerea mycelia growth and reduced 41% of gray mold severity of postharvest tomatoes. The 10% concentration of the culture filtrate of M. anisopliae inhibited 88.62% of colony radial growth as well as 63.85% of sclerotia germination and all conidia germination of B. cinerea. Furthermore, the culture filtrate of M. anisopliae retained its inhibitory effect against the radial growth of B. cinerea even after heating for 15 min at 100 °C. Feasible mechanisms of M. anisopliae involved in the control of B. cinerea were explored, and it was demonstrated that the plasma membrane of B. cinerea conidia was damaged by the product of metabolism of M. anisopliae. In addition, after treating with culture filtrate of M. anisopliae, the B. cinerea phenotype was shown to be abnormal, and cell organelles of B. cinerea mycelia were damaged significantly. A significant control efficacy of M. anisopliae against tomato gray mold was detected on both the detached leaf assay (84.24%) as well as the whole plant (72.38%). In addition, a 78% reduction in tomato fruit mold was detected at a 10% treated concentration of M. anisopliae. These findings suggest that M. anisopliae possesses potential as a biocontrol agent against tomato gray mold in the greenhouse and during the postharvest stage.The daily operation and maintenance work of railways are very dangerous. Railway employees often have safety accidents while working, and the safety citizenship behavior (SCB) of railway employees can effectively reduce the accident rate. Therefore, it is of great significance to identify the main safety constructs affecting the SCB of railway employees to minimize accidents. This paper puts forward a supposed model of the influence mechanism of safety leadership (SL) on employee SCB through the mediation of safety attitude (SA). A questionnaire was used with railway employees, and 238 valid responses were finally collected. A structural equation model (SEM) was used to explore the relationship between SL, SA and SCB. The results showed the SL is positively related to the SA, and it can further promote the SCB of railway employees. In addition, SA has a positive impact on employee SCB.Obesity is a comorbidity that plays a role in the development and severity of inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. The relationships between obesity and adipose tissue and the treatments given for inflammatory joint diseases are bidirectional. In fact, biological agents (bDMARDs) and targeted synthetic agents (tsDMARDs) may influence body weight and body composition of treated patients, while obesity in turn may influence clinical response to these agents. Obesity is a prevalent comorbidity mainly affecting patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) with specific phenotypes. Tumour necrosis factor alpha (TNFα) inhibitors have been associated with changes in body composition by improving lean mass, but also by significantly increasing fat mass, which localized toward the abdominal/visceral region. The IL-6 inhibitor tocilizumab is associated with an increase in lean mass without change in fat mass. The clinical response to TNFα inhibitors is attenuated by obesity, an effect that is less pronounced with IL-6 inhibitors and the B-cell depletion agent rituximab. Conversely, body weight has no influence on the response to the costimulation inhibitor abatacept. These effects may be of help to the physician in personalized medicine, and may guide the therapeutic choice in obese/overweight patients.Unsupervised feature extraction algorithms form one of the most important building blocks in machine learning systems. These algorithms are often adapted to the event-based domain to perform online learning in neuromorphic hardware. However, not designed for the purpose, such algorithms typically require significant simplification during implementation to meet hardware constraints, creating trade offs with performance. Furthermore, conventional feature extraction algorithms are not designed to generate useful intermediary signals which are valuable only in the context of neuromorphic hardware limitations. In this work a novel event-based feature extraction method is proposed that focuses on these issues. The algorithm operates via simple adaptive selection thresholds which allow a simpler implementation of network homeostasis than previous works by trading off a small amount of information loss in the form of missed events that fall outside the selection thresholds. The behavior of the selection thresholds and the output of the network as a whole are shown to provide uniquely useful signals indicating network weight convergence without the need to access network weights. A novel heuristic method for network size selection is proposed which makes use of noise events and their feature representations. The use of selection thresholds is shown to produce network activation patterns that predict classification accuracy allowing rapid evaluation and optimization of system parameters without the need to run ****-end classifiers. The feature extraction method is tested on both the N-MNIST (Neuromorphic-MNIST) benchmarking dataset and a dataset of airplanes passing through the field of view. Multiple configurations with different classifiers are tested with the results quantifying the resultant performance gains at each processing stage.Integrity of the musculoskeletal system is essential for the transfer of muscular contraction force to the associated bones. Tendons and skeletal muscles intertwine, but on a cellular level, the myotendinous junctions (MTJs) display a sharp transition zone with a highly specific molecular adaption. The function of MTJs could go beyond a mere structural role and might include homeostasis of this musculoskeletal tissue compound, thus also being involved in skeletal muscle regeneration. Repair processes recapitulate several developmental mechanisms, and as myotendinous interaction does occur already during development, MTJs could likewise contribute to muscle regeneration. Recent studies identified tendon-related, scleraxis-expressing cells that reside in close proximity to the MTJs and the muscle belly. As the muscle-specific function of these scleraxis positive cells is unknown, we compared the influence of two immortalized mesenchymal stem cell (MSC) lines-differing only by the overexpression of scleraxis-on myoblasts morphology, metabolism, migration, fusion, and alignment.
    Gray mold disease caused by Botrytis cinerea is a devastating disease that leads to serious financial loss. In this study, the entomopathogenic fungus Metarhizium anisopliae that acts against the gray mold pathogen B. cinerea was evaluated. M. anisopliae produced a significant inhibition zone in front of the B. https://www.selleckchem.com/products/emd-1214063.html cinerea colony in the dual culture test. In addition, volatile organic compounds generated by M. anisopliae were shown to have an inhibitory effect on B. cinerea mycelia growth and reduced 41% of gray mold severity of postharvest tomatoes. The 10% concentration of the culture filtrate of M. anisopliae inhibited 88.62% of colony radial growth as well as 63.85% of sclerotia germination and all conidia germination of B. cinerea. Furthermore, the culture filtrate of M. anisopliae retained its inhibitory effect against the radial growth of B. cinerea even after heating for 15 min at 100 °C. Feasible mechanisms of M. anisopliae involved in the control of B. cinerea were explored, and it was demonstrated that the plasma membrane of B. cinerea conidia was damaged by the product of metabolism of M. anisopliae. In addition, after treating with culture filtrate of M. anisopliae, the B. cinerea phenotype was shown to be abnormal, and cell organelles of B. cinerea mycelia were damaged significantly. A significant control efficacy of M. anisopliae against tomato gray mold was detected on both the detached leaf assay (84.24%) as well as the whole plant (72.38%). In addition, a 78% reduction in tomato fruit mold was detected at a 10% treated concentration of M. anisopliae. These findings suggest that M. anisopliae possesses potential as a biocontrol agent against tomato gray mold in the greenhouse and during the postharvest stage.The daily operation and maintenance work of railways are very dangerous. Railway employees often have safety accidents while working, and the safety citizenship behavior (SCB) of railway employees can effectively reduce the accident rate. Therefore, it is of great significance to identify the main safety constructs affecting the SCB of railway employees to minimize accidents. This paper puts forward a supposed model of the influence mechanism of safety leadership (SL) on employee SCB through the mediation of safety attitude (SA). A questionnaire was used with railway employees, and 238 valid responses were finally collected. A structural equation model (SEM) was used to explore the relationship between SL, SA and SCB. The results showed the SL is positively related to the SA, and it can further promote the SCB of railway employees. In addition, SA has a positive impact on employee SCB.Obesity is a comorbidity that plays a role in the development and severity of inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. The relationships between obesity and adipose tissue and the treatments given for inflammatory joint diseases are bidirectional. In fact, biological agents (bDMARDs) and targeted synthetic agents (tsDMARDs) may influence body weight and body composition of treated patients, while obesity in turn may influence clinical response to these agents. Obesity is a prevalent comorbidity mainly affecting patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) with specific phenotypes. Tumour necrosis factor alpha (TNFα) inhibitors have been associated with changes in body composition by improving lean mass, but also by significantly increasing fat mass, which localized toward the abdominal/visceral region. The IL-6 inhibitor tocilizumab is associated with an increase in lean mass without change in fat mass. The clinical response to TNFα inhibitors is attenuated by obesity, an effect that is less pronounced with IL-6 inhibitors and the B-cell depletion agent rituximab. Conversely, body weight has no influence on the response to the costimulation inhibitor abatacept. These effects may be of help to the physician in personalized medicine, and may guide the therapeutic choice in obese/overweight patients.Unsupervised feature extraction algorithms form one of the most important building blocks in machine learning systems. These algorithms are often adapted to the event-based domain to perform online learning in neuromorphic hardware. However, not designed for the purpose, such algorithms typically require significant simplification during implementation to meet hardware constraints, creating trade offs with performance. Furthermore, conventional feature extraction algorithms are not designed to generate useful intermediary signals which are valuable only in the context of neuromorphic hardware limitations. In this work a novel event-based feature extraction method is proposed that focuses on these issues. The algorithm operates via simple adaptive selection thresholds which allow a simpler implementation of network homeostasis than previous works by trading off a small amount of information loss in the form of missed events that fall outside the selection thresholds. The behavior of the selection thresholds and the output of the network as a whole are shown to provide uniquely useful signals indicating network weight convergence without the need to access network weights. A novel heuristic method for network size selection is proposed which makes use of noise events and their feature representations. The use of selection thresholds is shown to produce network activation patterns that predict classification accuracy allowing rapid evaluation and optimization of system parameters without the need to run back-end classifiers. The feature extraction method is tested on both the N-MNIST (Neuromorphic-MNIST) benchmarking dataset and a dataset of airplanes passing through the field of view. Multiple configurations with different classifiers are tested with the results quantifying the resultant performance gains at each processing stage.Integrity of the musculoskeletal system is essential for the transfer of muscular contraction force to the associated bones. Tendons and skeletal muscles intertwine, but on a cellular level, the myotendinous junctions (MTJs) display a sharp transition zone with a highly specific molecular adaption. The function of MTJs could go beyond a mere structural role and might include homeostasis of this musculoskeletal tissue compound, thus also being involved in skeletal muscle regeneration. Repair processes recapitulate several developmental mechanisms, and as myotendinous interaction does occur already during development, MTJs could likewise contribute to muscle regeneration. Recent studies identified tendon-related, scleraxis-expressing cells that reside in close proximity to the MTJs and the muscle belly. As the muscle-specific function of these scleraxis positive cells is unknown, we compared the influence of two immortalized mesenchymal stem cell (MSC) lines-differing only by the overexpression of scleraxis-on myoblasts morphology, metabolism, migration, fusion, and alignment.
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  • Cardiomyopathies are a heterogeneous group of cardiac diseases for which diagnosis and treatment are not always simple. The diagnosis of cardiomyopathy, in particular the etiology, comes from an integration between symptoms and results collected by several instrumental exams. The brain storming for the diagnosis includes also the identification of the "red flags", i.e. the pathognomonic features for each etiology that can drive the choice of appropriate diagnostic tests and therapy. In this review, we provide a step by step approach in order to help cardiologists, not specifically dedicated to cardiomyopathies, to draw the diagnosis, therapy and follow-up. This approach will be accompanied by the consultation of other specialists to discuss together the results of the exams performed and to deepen extracardiac signs and symptoms.Myocarditis is a complex inflammatory disease of the myocardium, occurring secondary to viral infections or autoimmune mechanisms in most cases. Among its multiple clinical manifestations, arrhythmias are often underdiagnosed, in spite of their important prognostic value. In particular, ventricular arrhythmias complicating either active or previous myocarditis, are a significant cause of sudden cardiac death, especially in young people. Because of the absence of clinical trials specifically addressing this topic, nowadays updated international guidelines report extremely generic recommendations about optimal clinical management of patients with arrhythmic myocarditis. This review aims at both (i) showing the state of the art about patients with myocarditis and arrhythmias (ventricular arrhythmias in particular); and (ii) suggesting optimal diagnostic and therapeutic strategies for these patients, based on the experience of a high-volume referral center for arrhythmic myocarditis and ventricular arrhythmia management.Acute pulmonary embolism (PE) still represents the third leading cause of cardiovascular mortality in developed countries. In this regard, the last European guidelines offer important suggestions on the management of the disease in daily clinical practice but, at the same time, they do not take into account the feasibility of the recommendations according to the local available resources, including the presence or lack of adequate healthcare facilities (cardiological intensive care unit, cath-lab) or specialists (cardiologist available on a 24 h basis, interventional cardiologist, cardiac surgeon, etc.) all over the day. In the real clinical practice, those recommendations should be adapted to the local available resources. The aim of this document is to provide some suggestions regarding the diagnosis and treatment of acute PE, according to the possible available resources in different local circumstances.BACKGROUND Double balloon enteroscopy (DBE) is a diagnosis and therapy method for suspected small bowel bleeding (SSBB). The data for emergent DBE is limited in overt SSBB cases. The aim of this study was to investigate the role of diagnosis and therapy of emergent DBE in patients with overt SSBB. MATERIAL AND METHODS The clinical and endoscopic data for patients with overt SSBB undergoing DBE in a single center from January 2010 to December 2017 were collected and analyzed. Emergent DBE was defined as DBE performed less than 3 days of last bleeding onset. https://www.selleckchem.com/products/mgh-cp1.html RESULTS A total of 265 DBEs in 265 patients with overt SSBB were enrolled (mean age, 44.7±17.3 years; 66.8% males). The patients were divided into 3 groups according to the timing of DBE less than 3 days (n=32), more than 3 days and less than 7 days (n=146), and more than 7 days (n=87) (first group was the emergent group, the latter 2 groups were the non-emergent groups). The diagnosis yield for the emergent group was significantly higher than the non-emergent groups (84.4% versus 65.1% or 59.8%, respectively, P7 days group 78.1%, 58.2% and 39.1%, respectively, P less then 0.05. The top 3 endoscopic treatments were hemostatic clips (21.9%), argon plasma coagulation (15.8%), and epinephrine injection (14.0%). CONCLUSIONS The emergent DBE had the highest yields for diagnosis and therapy. The study finding showed a pivotal role of emergent DBE in overt SSBB.The scattering of acoustic phonons by nonreciprocal spring defects inserted in an harmonic chain is investigated. The degree of nonreciprocity of the forces mediated by the defect springs is parameterized by a single quantity Δ that effectively takes into account the interaction of the coupled masses with hidden degrees of freedom of an underlying nonequilibrium system. We demonstrate a pronounced rectification effect with transmission having a preferential direction. Nonreciprocity also allows energy exchange between the system and the medium. Further, we show a cooperative action between defects mediated by resonant cavity modes. The influence of damping forces is also explored and shown to promote the rectification of the reflected vibrational wave component.Biocompatibility and neuron regenerating properties of various bioactive glass (BG)/Polyhydroxyalkanoate (PHA) blend composites were assessed in order to study their suitability for peripheral nerve tissue applications, specifically as lumen structures for nerve guidance conduits (NGCs). BG/PHA blend composites were fabricated using Bioactive glass® 45S5 (BG1) and BG 1393 (BG2) with the 2535 poly(3-hydroxyoctanoate/poly3-hydroxybutyrate), 2575 P(3HO)/P(3HB) blend (PHA blend). Various concentrations of each BG (0.5, 1.0 and 2.5 wt%) were used to determine the effect of BG on neuronal growth and differentiation, in single culture using NG108-15 neuronal cells and in a co-culture along with RN22 Schwann cells. NG108-15 cells exhibited good growth and differentiation on all the PHA blend composites showing that both BGs have good biocompatibility at 0.5, 1.0 and 2.5 wt% within the PHA blend. The Young's modulus values displayed by all the PHA blend/BG composites ranged from 385.6 MPa to 1792.6 MPa, which are able to provide the required support and protective effect for regeneration of peripheral nerves. More specifically, the tensile strength obtained in the PHA blend/BG1 (1.0 wt%) (10.0 ± 0.6 MPa) was found to be similar to that of rabbit peroneal nerve. This composite also exhibited the best biological performance in supporting growth and neuronal differentiation among all the substrates. The neurite extension on this composite was found to be remarkable with the neurites forming a complex connection network. Creative Commons Attribution license.
    Cardiomyopathies are a heterogeneous group of cardiac diseases for which diagnosis and treatment are not always simple. The diagnosis of cardiomyopathy, in particular the etiology, comes from an integration between symptoms and results collected by several instrumental exams. The brain storming for the diagnosis includes also the identification of the "red flags", i.e. the pathognomonic features for each etiology that can drive the choice of appropriate diagnostic tests and therapy. In this review, we provide a step by step approach in order to help cardiologists, not specifically dedicated to cardiomyopathies, to draw the diagnosis, therapy and follow-up. This approach will be accompanied by the consultation of other specialists to discuss together the results of the exams performed and to deepen extracardiac signs and symptoms.Myocarditis is a complex inflammatory disease of the myocardium, occurring secondary to viral infections or autoimmune mechanisms in most cases. Among its multiple clinical manifestations, arrhythmias are often underdiagnosed, in spite of their important prognostic value. In particular, ventricular arrhythmias complicating either active or previous myocarditis, are a significant cause of sudden cardiac death, especially in young people. Because of the absence of clinical trials specifically addressing this topic, nowadays updated international guidelines report extremely generic recommendations about optimal clinical management of patients with arrhythmic myocarditis. This review aims at both (i) showing the state of the art about patients with myocarditis and arrhythmias (ventricular arrhythmias in particular); and (ii) suggesting optimal diagnostic and therapeutic strategies for these patients, based on the experience of a high-volume referral center for arrhythmic myocarditis and ventricular arrhythmia management.Acute pulmonary embolism (PE) still represents the third leading cause of cardiovascular mortality in developed countries. In this regard, the last European guidelines offer important suggestions on the management of the disease in daily clinical practice but, at the same time, they do not take into account the feasibility of the recommendations according to the local available resources, including the presence or lack of adequate healthcare facilities (cardiological intensive care unit, cath-lab) or specialists (cardiologist available on a 24 h basis, interventional cardiologist, cardiac surgeon, etc.) all over the day. In the real clinical practice, those recommendations should be adapted to the local available resources. The aim of this document is to provide some suggestions regarding the diagnosis and treatment of acute PE, according to the possible available resources in different local circumstances.BACKGROUND Double balloon enteroscopy (DBE) is a diagnosis and therapy method for suspected small bowel bleeding (SSBB). The data for emergent DBE is limited in overt SSBB cases. The aim of this study was to investigate the role of diagnosis and therapy of emergent DBE in patients with overt SSBB. MATERIAL AND METHODS The clinical and endoscopic data for patients with overt SSBB undergoing DBE in a single center from January 2010 to December 2017 were collected and analyzed. Emergent DBE was defined as DBE performed less than 3 days of last bleeding onset. https://www.selleckchem.com/products/mgh-cp1.html RESULTS A total of 265 DBEs in 265 patients with overt SSBB were enrolled (mean age, 44.7±17.3 years; 66.8% males). The patients were divided into 3 groups according to the timing of DBE less than 3 days (n=32), more than 3 days and less than 7 days (n=146), and more than 7 days (n=87) (first group was the emergent group, the latter 2 groups were the non-emergent groups). The diagnosis yield for the emergent group was significantly higher than the non-emergent groups (84.4% versus 65.1% or 59.8%, respectively, P7 days group 78.1%, 58.2% and 39.1%, respectively, P less then 0.05. The top 3 endoscopic treatments were hemostatic clips (21.9%), argon plasma coagulation (15.8%), and epinephrine injection (14.0%). CONCLUSIONS The emergent DBE had the highest yields for diagnosis and therapy. The study finding showed a pivotal role of emergent DBE in overt SSBB.The scattering of acoustic phonons by nonreciprocal spring defects inserted in an harmonic chain is investigated. The degree of nonreciprocity of the forces mediated by the defect springs is parameterized by a single quantity Δ that effectively takes into account the interaction of the coupled masses with hidden degrees of freedom of an underlying nonequilibrium system. We demonstrate a pronounced rectification effect with transmission having a preferential direction. Nonreciprocity also allows energy exchange between the system and the medium. Further, we show a cooperative action between defects mediated by resonant cavity modes. The influence of damping forces is also explored and shown to promote the rectification of the reflected vibrational wave component.Biocompatibility and neuron regenerating properties of various bioactive glass (BG)/Polyhydroxyalkanoate (PHA) blend composites were assessed in order to study their suitability for peripheral nerve tissue applications, specifically as lumen structures for nerve guidance conduits (NGCs). BG/PHA blend composites were fabricated using Bioactive glass® 45S5 (BG1) and BG 1393 (BG2) with the 2535 poly(3-hydroxyoctanoate/poly3-hydroxybutyrate), 2575 P(3HO)/P(3HB) blend (PHA blend). Various concentrations of each BG (0.5, 1.0 and 2.5 wt%) were used to determine the effect of BG on neuronal growth and differentiation, in single culture using NG108-15 neuronal cells and in a co-culture along with RN22 Schwann cells. NG108-15 cells exhibited good growth and differentiation on all the PHA blend composites showing that both BGs have good biocompatibility at 0.5, 1.0 and 2.5 wt% within the PHA blend. The Young's modulus values displayed by all the PHA blend/BG composites ranged from 385.6 MPa to 1792.6 MPa, which are able to provide the required support and protective effect for regeneration of peripheral nerves. More specifically, the tensile strength obtained in the PHA blend/BG1 (1.0 wt%) (10.0 ± 0.6 MPa) was found to be similar to that of rabbit peroneal nerve. This composite also exhibited the best biological performance in supporting growth and neuronal differentiation among all the substrates. The neurite extension on this composite was found to be remarkable with the neurites forming a complex connection network. Creative Commons Attribution license.
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  • Trehalose and glycogen content and trehalase activity were regulated by differential expression of TRE and TPS genes. Female beetles weighed more than males and survived in low temperatures for longer periods of time, regardless of elytra colour, suggesting that mass is a stronger predictor of overwintering survival rather than colour morph. https://www.selleckchem.com/products/stemRegenin-1.html Our results provide a guide for comparing cold resistance in insects and a theoretical basis for cold storage of H. axyridis for use as natural enemies of pests in biological control programs.[This corrects the article DOI 10.1371/journal.pone.0224222.].A total of 201 patients with major depressive disorder from four hospitals in Malaysia were followed up for 5 years to determine the prognostic factors of recurrent major depressive disorder that could potentially contribute to improving the management of MDD patients. For each individual patient, at the time of recruitment as part of a case-control study, information was collected on recent threatening life events, personality and social and occupational functioning, while blood samples were collected to genotype single nucleotide polymorphisms of vitamin D receptor (VDR), zinc transporter-3 (ZnT3), dopamine transporter-1 (DAT1), brain-derived neurotropic factor (BDNF), serotonin receptor 1A (HT1A) and 2A (HT2A) genes. Kaplan-Meier and Cox-regression were used to estimate hazard functions for recurrence of major depressive disorder. Individuals with severe MDD in previous major depressive episodes had five and a half times higher hazard of developing recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631-18.994, p = 0.006). Individuals who scored higher on social avoidance had three and a half times higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349-9.209; p = 0.010). There was significant interaction between ApaI +64978C>A single nucleotide polymorphism and severity. The hazard ratio increased by 6.4 times from mild and moderate to severe MDD for A/A genotype while that for C/A genotype increased by 11.3 times. Social avoidance and severity of depression at first episode were prognostic of recurrence. Screening for personality factors at first encounter with MDD patients needs to be considered as part of the clinical practice. For those at risk of recurrence in relation to social avoidance, the psychological intervention prescribed should be customized to focus on this modifiable factor. Prompt and appropriate management of severe MDD is recommended to reduce risk of recurrence.INTRODUCTION The management of minor conditions represents a significant burden for urgent and emergency care services and reduces the capacity to provide specialist care for higher acuity healthcare need. A pilot Digital Minor Illness Service (DMIRS) was commenced in the North East of England in December 2017 to feasibility test the NHS 111 referral to community pharmacy for patients presenting with minor conditions. OBJECTIVES A formative evaluation of the service activity data and qualitative investigation of stakeholders involved in the service design, management, delivery and use, aims to present and investigate the service outcomes. METHOD Routine service activity data was evaluated during Jan-Dec 2018 to investigate the demographics of patients included in the service; the presenting conditions; and how those referrals were managed by community pharmacies. Semi-structured interviews with NHS 111 call handlers, project team members, community pharmacists and patients were undertaken to investigate the dound the management of minor conditions within the urgent and emergency care setting.Mitochondria are mostly inherited by maternal via, that is, only mitochondria from eggs are retained in the embryos. However, this general assumption of uniparentally transmitted, homoplasmic and non-recombining mitochondrial genomes is becoming more and more controversial. The presence of different sequences of mtDNA within a cell or individual, known as heteroplasmy, is increasingly reported in several taxon of animals, such as molluscs, arthropods and vertebrates. In this work, a considerable frequency of heteroplasmy were detected in the COI and 16S genes of the spider crab Maja brachydactyla, possibly associated to hybridisation with the congeneric species Maja squinado. This finding is a fact to keep in mind before addressing molecular analyses based on mitochondrial markers, since the assumption of maternal inheritance could lead to erroneous results. As M. brachydactyla is a commercial species, heteroplasmy is an important aspect to take into account for the fisheries management of this resource, since effective population size could be overestimated.Spatio-temporal variation in resource availability leads to a variety of animal movement strategies. In the case of ungulates, temporally unpredictable landscapes are associated with nomadism, while high predictability in the resource distribution favours migratory or sedentary behaviours depending on the spatial and temporal scale of landscape dynamics. As most of the surveys on moose (Alces alces) movement behaviours in Europe have been conducted on Scandinavian populations, little is known about the movement strategies of moose at the southern edge of the species' range. We expected that decreasing habitat patchiness in central Europe would be associated with the prevalence of migratory behaviours. To verify this hypothesis, we analysed 32 moose fitted with GPS collars from two study areas in eastern Poland which differed in a level of habitat patchiness. We classified moose movements using the net squared displacement method. As presumed, lower patchiness in the Biebrza study site was associated with the predominance of individuals migrating short-distance, while in more patchy landscape of Polesie, resident moose dominated. At the individual level, the propensity of moose to migrate decreased with increasing abundance of forest habitats in their summer ranges. In addition, the parameters (migration distance, timing and duration) for migratory individuals varied substantially between individuals and years. Yet, in spring individual moose expressed a consistent migration timing across years. There was little synchronization of migration timing between individuals from the same population both in spring and autumn, which may have been related to mild weather conditions. We observed that moose postponed their migrations and started movement toward summer ranges at a similar time window in years when spring was delayed due to harsh weather. Hence, in light of global warming, we presume further changes in animal movements will arise.
    Trehalose and glycogen content and trehalase activity were regulated by differential expression of TRE and TPS genes. Female beetles weighed more than males and survived in low temperatures for longer periods of time, regardless of elytra colour, suggesting that mass is a stronger predictor of overwintering survival rather than colour morph. https://www.selleckchem.com/products/stemRegenin-1.html Our results provide a guide for comparing cold resistance in insects and a theoretical basis for cold storage of H. axyridis for use as natural enemies of pests in biological control programs.[This corrects the article DOI 10.1371/journal.pone.0224222.].A total of 201 patients with major depressive disorder from four hospitals in Malaysia were followed up for 5 years to determine the prognostic factors of recurrent major depressive disorder that could potentially contribute to improving the management of MDD patients. For each individual patient, at the time of recruitment as part of a case-control study, information was collected on recent threatening life events, personality and social and occupational functioning, while blood samples were collected to genotype single nucleotide polymorphisms of vitamin D receptor (VDR), zinc transporter-3 (ZnT3), dopamine transporter-1 (DAT1), brain-derived neurotropic factor (BDNF), serotonin receptor 1A (HT1A) and 2A (HT2A) genes. Kaplan-Meier and Cox-regression were used to estimate hazard functions for recurrence of major depressive disorder. Individuals with severe MDD in previous major depressive episodes had five and a half times higher hazard of developing recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631-18.994, p = 0.006). Individuals who scored higher on social avoidance had three and a half times higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349-9.209; p = 0.010). There was significant interaction between ApaI +64978C>A single nucleotide polymorphism and severity. The hazard ratio increased by 6.4 times from mild and moderate to severe MDD for A/A genotype while that for C/A genotype increased by 11.3 times. Social avoidance and severity of depression at first episode were prognostic of recurrence. Screening for personality factors at first encounter with MDD patients needs to be considered as part of the clinical practice. For those at risk of recurrence in relation to social avoidance, the psychological intervention prescribed should be customized to focus on this modifiable factor. Prompt and appropriate management of severe MDD is recommended to reduce risk of recurrence.INTRODUCTION The management of minor conditions represents a significant burden for urgent and emergency care services and reduces the capacity to provide specialist care for higher acuity healthcare need. A pilot Digital Minor Illness Service (DMIRS) was commenced in the North East of England in December 2017 to feasibility test the NHS 111 referral to community pharmacy for patients presenting with minor conditions. OBJECTIVES A formative evaluation of the service activity data and qualitative investigation of stakeholders involved in the service design, management, delivery and use, aims to present and investigate the service outcomes. METHOD Routine service activity data was evaluated during Jan-Dec 2018 to investigate the demographics of patients included in the service; the presenting conditions; and how those referrals were managed by community pharmacies. Semi-structured interviews with NHS 111 call handlers, project team members, community pharmacists and patients were undertaken to investigate the dound the management of minor conditions within the urgent and emergency care setting.Mitochondria are mostly inherited by maternal via, that is, only mitochondria from eggs are retained in the embryos. However, this general assumption of uniparentally transmitted, homoplasmic and non-recombining mitochondrial genomes is becoming more and more controversial. The presence of different sequences of mtDNA within a cell or individual, known as heteroplasmy, is increasingly reported in several taxon of animals, such as molluscs, arthropods and vertebrates. In this work, a considerable frequency of heteroplasmy were detected in the COI and 16S genes of the spider crab Maja brachydactyla, possibly associated to hybridisation with the congeneric species Maja squinado. This finding is a fact to keep in mind before addressing molecular analyses based on mitochondrial markers, since the assumption of maternal inheritance could lead to erroneous results. As M. brachydactyla is a commercial species, heteroplasmy is an important aspect to take into account for the fisheries management of this resource, since effective population size could be overestimated.Spatio-temporal variation in resource availability leads to a variety of animal movement strategies. In the case of ungulates, temporally unpredictable landscapes are associated with nomadism, while high predictability in the resource distribution favours migratory or sedentary behaviours depending on the spatial and temporal scale of landscape dynamics. As most of the surveys on moose (Alces alces) movement behaviours in Europe have been conducted on Scandinavian populations, little is known about the movement strategies of moose at the southern edge of the species' range. We expected that decreasing habitat patchiness in central Europe would be associated with the prevalence of migratory behaviours. To verify this hypothesis, we analysed 32 moose fitted with GPS collars from two study areas in eastern Poland which differed in a level of habitat patchiness. We classified moose movements using the net squared displacement method. As presumed, lower patchiness in the Biebrza study site was associated with the predominance of individuals migrating short-distance, while in more patchy landscape of Polesie, resident moose dominated. At the individual level, the propensity of moose to migrate decreased with increasing abundance of forest habitats in their summer ranges. In addition, the parameters (migration distance, timing and duration) for migratory individuals varied substantially between individuals and years. Yet, in spring individual moose expressed a consistent migration timing across years. There was little synchronization of migration timing between individuals from the same population both in spring and autumn, which may have been related to mild weather conditions. We observed that moose postponed their migrations and started movement toward summer ranges at a similar time window in years when spring was delayed due to harsh weather. Hence, in light of global warming, we presume further changes in animal movements will arise.
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  • In the current study, we aimed to assess the impact of antibiotics (ATB) and metabolic parameters on clinical outcome of non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI).

    Data from fifty NSCLC patients referred for ICI between December 2015 and May 2019 were analyzed. All patients underwent 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) and contrast-enhanced CT at baseline and for response assessment after 6-8 weeks. Patients who received ATB within 1 month before or after the first dose of ICI were compared with those who did not. Response assessment according to iRECIST and EORTC was evaluated, as well as progression-free survival (PFS) and overall survival (OS). For semi-quantitative parameters, we computed metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their variations (∆).

    Twenty NSCLC cases of 50 (40%) had received ATB. Patients receiving ATB had a higher number of metastases (
    = 0.046), and were associated with an elevated tumor burden, expressed by TLG (687 vs. 235.3,
    = 0.007) and MTV (125.6 vs. 40.6,
    = 0.002), compared to no-ATB patients. According to iRECIST, progressive disease rate was significantly higher for ATB group (64.7% vs. 27.6%,
    = 0.029). Likewise, PFS was shorter for ATB compared to no-ATB (median 4.1 vs. 12.4 months,
    = 0.004), while no difference for OS was detected. On multivariate analysis, the effect of ATB remained significant for poor PFS along with performance status (ECOG ≥ 1), and ∆SUVmax.

    ATB therapy seems to be associated with a worse treatment response, PFS, and higher metabolic tumor burden in NSCLC patients treated with ICI.
    ATB therapy seems to be associated with a worse treatment response, PFS, and higher metabolic tumor burden in NSCLC patients treated with ICI.Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. https://www.selleckchem.com/products/sr-0813.html Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.Recently, hemp (Cannabis Sativa L.) was rediscovery as a plant that offers a wide variety of applications (textile, pharmaceuticals, construction, etc.), including also the use in animal and human nutrition. The inclusion of whole seeds and co-products obtained by processing of seeds (cake, meal, and oil) in the diets of farm animals can allow the transfer of bioactive substances to human food. Few publications are available on the use of hemp in dairy ruminants but some authors reported a positive effect on the fatty acids profile of milk and cheese with an increase of n-3 fatty acids and c9,t11 conjugated linoleic acid. The protein content, amino acids profile, and rumen undegradable protein (RUP) of hempseed and co-products of hemp appear interesting and suitable for ruminant nutrition. Negative effects of anti-nutritional factors (i.e., phytate) are not observed. However, the researches on the effects of the use of hempseed and co-products in diets for dairy ruminants do not allow to suggest optimal levels of inclusion. In addition, no data are published on the use of whole or part of the hemp plant as forage, as another possibility to use the hemp in the perspective of the circular economy.This study examines the influence of self-rated health and subjective economic status on the life satisfaction of older Chinese immigrants in the United States. Data were obtained from a cross-sectional survey of 205 older Chinese immigrants aged 66 to 90 years living in Los Angeles and Honolulu. Ordinary Least Squares (OLS) regression analysis was employed to explore the independent effects of self-rated health and subjective economic status. The results demonstrated that self-rated health and subjective economic status were positively associated with life satisfaction. This cross-sectional study provides empirical evidence that self-rated health and subjective economic status are directly associated with subjective life satisfaction among older Chinese immigrants.Due to the inappropriate use and overuse of antibiotics, the emergence and spread of antibiotic-resistant bacteria are increasing and have become a major threat to human health. A key factor in the treatment of bacterial infections and slowing down the emergence of antibiotic resistance is to perform antimicrobial susceptibility testing (AST) of infecting bacteria rapidly to prescribe appropriate drugs and reduce the use of broad-spectrum antibiotics. Current phenotypic AST methods based on the detection of bacterial growth are generally reliable but are too slow. There is an urgent need for new methods that can perform AST rapidly. Bacterial metabolism is a fast process, as bacterial cells double about every 20 to 30 min for fast-growing species. Moreover, bacterial metabolism has shown to be related to drug resistance, so a comparison of differences in microbial metabolic processes in the presence or absence of antimicrobials provides an alternative approach to traditional culture for faster AST. In this review, we summarize recent developments in rapid AST methods through metabolic profiling of bacteria under antibiotic treatment.
    In the current study, we aimed to assess the impact of antibiotics (ATB) and metabolic parameters on clinical outcome of non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). Data from fifty NSCLC patients referred for ICI between December 2015 and May 2019 were analyzed. All patients underwent 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) and contrast-enhanced CT at baseline and for response assessment after 6-8 weeks. Patients who received ATB within 1 month before or after the first dose of ICI were compared with those who did not. Response assessment according to iRECIST and EORTC was evaluated, as well as progression-free survival (PFS) and overall survival (OS). For semi-quantitative parameters, we computed metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their variations (∆). Twenty NSCLC cases of 50 (40%) had received ATB. Patients receiving ATB had a higher number of metastases ( = 0.046), and were associated with an elevated tumor burden, expressed by TLG (687 vs. 235.3, = 0.007) and MTV (125.6 vs. 40.6, = 0.002), compared to no-ATB patients. According to iRECIST, progressive disease rate was significantly higher for ATB group (64.7% vs. 27.6%, = 0.029). Likewise, PFS was shorter for ATB compared to no-ATB (median 4.1 vs. 12.4 months, = 0.004), while no difference for OS was detected. On multivariate analysis, the effect of ATB remained significant for poor PFS along with performance status (ECOG ≥ 1), and ∆SUVmax. ATB therapy seems to be associated with a worse treatment response, PFS, and higher metabolic tumor burden in NSCLC patients treated with ICI. ATB therapy seems to be associated with a worse treatment response, PFS, and higher metabolic tumor burden in NSCLC patients treated with ICI.Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. https://www.selleckchem.com/products/sr-0813.html Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.Recently, hemp (Cannabis Sativa L.) was rediscovery as a plant that offers a wide variety of applications (textile, pharmaceuticals, construction, etc.), including also the use in animal and human nutrition. The inclusion of whole seeds and co-products obtained by processing of seeds (cake, meal, and oil) in the diets of farm animals can allow the transfer of bioactive substances to human food. Few publications are available on the use of hemp in dairy ruminants but some authors reported a positive effect on the fatty acids profile of milk and cheese with an increase of n-3 fatty acids and c9,t11 conjugated linoleic acid. The protein content, amino acids profile, and rumen undegradable protein (RUP) of hempseed and co-products of hemp appear interesting and suitable for ruminant nutrition. Negative effects of anti-nutritional factors (i.e., phytate) are not observed. However, the researches on the effects of the use of hempseed and co-products in diets for dairy ruminants do not allow to suggest optimal levels of inclusion. In addition, no data are published on the use of whole or part of the hemp plant as forage, as another possibility to use the hemp in the perspective of the circular economy.This study examines the influence of self-rated health and subjective economic status on the life satisfaction of older Chinese immigrants in the United States. Data were obtained from a cross-sectional survey of 205 older Chinese immigrants aged 66 to 90 years living in Los Angeles and Honolulu. Ordinary Least Squares (OLS) regression analysis was employed to explore the independent effects of self-rated health and subjective economic status. The results demonstrated that self-rated health and subjective economic status were positively associated with life satisfaction. This cross-sectional study provides empirical evidence that self-rated health and subjective economic status are directly associated with subjective life satisfaction among older Chinese immigrants.Due to the inappropriate use and overuse of antibiotics, the emergence and spread of antibiotic-resistant bacteria are increasing and have become a major threat to human health. A key factor in the treatment of bacterial infections and slowing down the emergence of antibiotic resistance is to perform antimicrobial susceptibility testing (AST) of infecting bacteria rapidly to prescribe appropriate drugs and reduce the use of broad-spectrum antibiotics. Current phenotypic AST methods based on the detection of bacterial growth are generally reliable but are too slow. There is an urgent need for new methods that can perform AST rapidly. Bacterial metabolism is a fast process, as bacterial cells double about every 20 to 30 min for fast-growing species. Moreover, bacterial metabolism has shown to be related to drug resistance, so a comparison of differences in microbial metabolic processes in the presence or absence of antimicrobials provides an alternative approach to traditional culture for faster AST. In this review, we summarize recent developments in rapid AST methods through metabolic profiling of bacteria under antibiotic treatment.
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  • r therapy-resistant, genetically predisposed colon cancer.Maintenance of genomic diversity is critically dependent on gene regulation at the transcriptional level. This occurs via the interaction of regulatory DNA sequence motifs with DNA-binding transcription factors. The zinc finger, BED-type (ZBED) gene family contains major DNA-binding motifs present in human transcriptional factors. It encodes proteins that present markedly diverse regulatory functions. ZBED1 has similar structural and functional properties to its Drosophila homolog DNA replication-related element-binding factor (DREF) and plays a critical role in the regulation of transcription. ZBED1 regulates the expression of several genes associated with cell proliferation, including cell cycle regulation, chromatin remodeling and protein metabolism, and some genes associated with apoptosis and differentiation. https://www.selleckchem.com/products/rcm-1.html In the present review, the origin, structure and functional role of ZBED1 were comprehensively assessed. In addition, the similarities and differences between ZBED1 and its Drosophila homolog DREF were highlighted, and future research directions, particularly in the area of clinical cancer, were discussed.Cancer treatment remains a serious challenge worldwide. Thus, finding novel antitumour agents is of great importance. In the present study, nine new benzenesulphonohydrazide derivatives (1-9) were synthesized, and the chemical structures of the obtained compounds were confirmed by spectral analysis methods, including IR, 1H nuclear magnetic resonance (NMR) and 13C NMR. Experimental lipophilicity values were established using reversed phase-high performance thin layer chromatography. The antiproliferative activity of the synthesized compounds was tested against three tumour cell lines (769-P, HepG2 and NCI-H2170) and one normal cell line (Vero). Among the newly developed molecules, compound 4 exhibited generally the highest cytotoxicity across all tumour cell lines, and it was highly selective. However, higher selectivity towards the tested cancer cell lines was observed using compound 2, when compared with compound 4, which also exhibited significant antiproliferative activity against these tumour cells. In 769-P cells, compounds 5 and 6 were the most selective among all tested compounds. Compound 5 exhibited high cytotoxicity with an estimated IC50 value of 1.94 µM. In the NCI-H2170 cell line, compound 7 was the most cytotoxic and the most selective. In brief, the combination of fluorine and bromine substituents at the phenyl ring showed the most promising results, exerting high cytotoxicity and selectivity towards cancer cells. The renal adenocarcinoma cell line (769-P) appeared to be the most sensitive to the anticancer properties of the novel benzenesulphonohydrazones.This study explored the changes and predictive value of miR-34a in nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), and its association with cognitive function. Fifty NPC patients admitted to Shunde Hospital, and another fifty healthy individuals were assigned into treated group and control group, respectively. Patients in the treated group received 3 courses of CCRT. The relative expression of miR-34a in the two groups was detected, and the cognitive function of patients was assessed. Diagnostic and predictive values of miR-34a in advanced NPC were analyzed. The expression of miR-34a in the control group was significantly higher than that in the treated group (t=13.364, P less then 0.001), with an area under the curve (AUC) of 0.979. The expression of miR-34a was significantly upregulated after treatment (t=4.559, P less then 0.001). After treatment, there were 32 complete remission (CR) patients and 18 partial remission (PR) patients. According to efficacy, CR patients were classified as significant group and PR patients as general group. The expression of miR-34a in the significant group was higher than that in the general group before treatment (t=4.704, P less then 0.001), with an AUC of 0.852. The Montreal Cognitive Assessment (****) score was significantly decreased after treatment (t=13.042, P less then 0.001). The expression of miR-34a was positively correlated with the **** score after treatment, that is, **** score gradually increased with the upregulation of miR-34a expression (r=0.379, P=0.006). There is a positive correlation between miR-34a and cognitive function of patients. Moreover, the expression of miR-34a can be used as a potential predictor of the efficacy of CCRT in patients with NPC.The present study aimed at investigating how long-chain non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) regulates the malignant biological behavior of osteosarcoma cells. Tumor tissues and adjacent tissues of 30 patients with osteosarcoma were collected, and the expression levels of lncRNA TUSC7 and miR-375 were detected by RT-qPCR. lncRNA TUSC7 mimic and miR-375 mimic transfection models were established in MG63 osteosarcoma cells, and Transwell assays were used to detect the migration ability of MG63 cells. An MTT assay was used to assess the proliferation ability of MG63 cells. lncRNA TUSC7 in osteosarcoma tissue was significantly lower than that of adjacent tissues, while miR-375 levels were significantly higher than that of adjacent tissues; the two levels have a negative correlation. lncRNA TUSC7 mimic inhibited MG63 proliferation and migration abilities. miR-375 mimic promoted MG63 proliferation and migration abilities. The lncRNA TUSC7 mimic and miR-375 mimic co-transfection system could partially rescue the inhibition of lncRNA TUSC7 mimic on MG63 cells. In conclusion, lncRNA TUSC7 inhibited the proliferation and migration of MG63 osteosarcoma cells by regulating miR-375.Colorectal cancer is an aggressive disease with a poor prognosis and low survival rate at the advanced stage, therefore new innovative targets are urgently required. Flurbiprofen has been reported to exhibit therapeutic effects in other types of cancer, such as esophageal cancer, breast cancer and colorectal cancer. Therefore, the present study aimed to investigate the function of flurbiprofen in colorectal cancer. SW620 colorectal cancer cells were treated with different concentrations of flurbiprofen to determine the optimum concentration. Subsequently, COX2 expression affected by flurbiprofen was tested using western blotting, reverse transcription-quantitative PCR and immunofluorescence. Enzyme-linked immunosorbent assay was used to determine the levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β. Cell Counting Kit-8, colony formation and flow cytometry assays were used to assess the proliferation and apoptosis of SW620 cells in various groups. Western blotting was performed to investigate the expression of proliferation-, apoptosis- and migration-related proteins after different treatments.
    r therapy-resistant, genetically predisposed colon cancer.Maintenance of genomic diversity is critically dependent on gene regulation at the transcriptional level. This occurs via the interaction of regulatory DNA sequence motifs with DNA-binding transcription factors. The zinc finger, BED-type (ZBED) gene family contains major DNA-binding motifs present in human transcriptional factors. It encodes proteins that present markedly diverse regulatory functions. ZBED1 has similar structural and functional properties to its Drosophila homolog DNA replication-related element-binding factor (DREF) and plays a critical role in the regulation of transcription. ZBED1 regulates the expression of several genes associated with cell proliferation, including cell cycle regulation, chromatin remodeling and protein metabolism, and some genes associated with apoptosis and differentiation. https://www.selleckchem.com/products/rcm-1.html In the present review, the origin, structure and functional role of ZBED1 were comprehensively assessed. In addition, the similarities and differences between ZBED1 and its Drosophila homolog DREF were highlighted, and future research directions, particularly in the area of clinical cancer, were discussed.Cancer treatment remains a serious challenge worldwide. Thus, finding novel antitumour agents is of great importance. In the present study, nine new benzenesulphonohydrazide derivatives (1-9) were synthesized, and the chemical structures of the obtained compounds were confirmed by spectral analysis methods, including IR, 1H nuclear magnetic resonance (NMR) and 13C NMR. Experimental lipophilicity values were established using reversed phase-high performance thin layer chromatography. The antiproliferative activity of the synthesized compounds was tested against three tumour cell lines (769-P, HepG2 and NCI-H2170) and one normal cell line (Vero). Among the newly developed molecules, compound 4 exhibited generally the highest cytotoxicity across all tumour cell lines, and it was highly selective. However, higher selectivity towards the tested cancer cell lines was observed using compound 2, when compared with compound 4, which also exhibited significant antiproliferative activity against these tumour cells. In 769-P cells, compounds 5 and 6 were the most selective among all tested compounds. Compound 5 exhibited high cytotoxicity with an estimated IC50 value of 1.94 µM. In the NCI-H2170 cell line, compound 7 was the most cytotoxic and the most selective. In brief, the combination of fluorine and bromine substituents at the phenyl ring showed the most promising results, exerting high cytotoxicity and selectivity towards cancer cells. The renal adenocarcinoma cell line (769-P) appeared to be the most sensitive to the anticancer properties of the novel benzenesulphonohydrazones.This study explored the changes and predictive value of miR-34a in nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), and its association with cognitive function. Fifty NPC patients admitted to Shunde Hospital, and another fifty healthy individuals were assigned into treated group and control group, respectively. Patients in the treated group received 3 courses of CCRT. The relative expression of miR-34a in the two groups was detected, and the cognitive function of patients was assessed. Diagnostic and predictive values of miR-34a in advanced NPC were analyzed. The expression of miR-34a in the control group was significantly higher than that in the treated group (t=13.364, P less then 0.001), with an area under the curve (AUC) of 0.979. The expression of miR-34a was significantly upregulated after treatment (t=4.559, P less then 0.001). After treatment, there were 32 complete remission (CR) patients and 18 partial remission (PR) patients. According to efficacy, CR patients were classified as significant group and PR patients as general group. The expression of miR-34a in the significant group was higher than that in the general group before treatment (t=4.704, P less then 0.001), with an AUC of 0.852. The Montreal Cognitive Assessment (MoCA) score was significantly decreased after treatment (t=13.042, P less then 0.001). The expression of miR-34a was positively correlated with the MoCA score after treatment, that is, MoCA score gradually increased with the upregulation of miR-34a expression (r=0.379, P=0.006). There is a positive correlation between miR-34a and cognitive function of patients. Moreover, the expression of miR-34a can be used as a potential predictor of the efficacy of CCRT in patients with NPC.The present study aimed at investigating how long-chain non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) regulates the malignant biological behavior of osteosarcoma cells. Tumor tissues and adjacent tissues of 30 patients with osteosarcoma were collected, and the expression levels of lncRNA TUSC7 and miR-375 were detected by RT-qPCR. lncRNA TUSC7 mimic and miR-375 mimic transfection models were established in MG63 osteosarcoma cells, and Transwell assays were used to detect the migration ability of MG63 cells. An MTT assay was used to assess the proliferation ability of MG63 cells. lncRNA TUSC7 in osteosarcoma tissue was significantly lower than that of adjacent tissues, while miR-375 levels were significantly higher than that of adjacent tissues; the two levels have a negative correlation. lncRNA TUSC7 mimic inhibited MG63 proliferation and migration abilities. miR-375 mimic promoted MG63 proliferation and migration abilities. The lncRNA TUSC7 mimic and miR-375 mimic co-transfection system could partially rescue the inhibition of lncRNA TUSC7 mimic on MG63 cells. In conclusion, lncRNA TUSC7 inhibited the proliferation and migration of MG63 osteosarcoma cells by regulating miR-375.Colorectal cancer is an aggressive disease with a poor prognosis and low survival rate at the advanced stage, therefore new innovative targets are urgently required. Flurbiprofen has been reported to exhibit therapeutic effects in other types of cancer, such as esophageal cancer, breast cancer and colorectal cancer. Therefore, the present study aimed to investigate the function of flurbiprofen in colorectal cancer. SW620 colorectal cancer cells were treated with different concentrations of flurbiprofen to determine the optimum concentration. Subsequently, COX2 expression affected by flurbiprofen was tested using western blotting, reverse transcription-quantitative PCR and immunofluorescence. Enzyme-linked immunosorbent assay was used to determine the levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β. Cell Counting Kit-8, colony formation and flow cytometry assays were used to assess the proliferation and apoptosis of SW620 cells in various groups. Western blotting was performed to investigate the expression of proliferation-, apoptosis- and migration-related proteins after different treatments.
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  • Data were analyzed using One-way ANOVA (α  =  0.05). Both the GO-coated NiTi and GO/Ag-coated NiTi alloys showed better corrosion resistance, a lower rate of corrosion, and higher protection efficiency than the bare NiTi alloy. The coated NiTi alloys were biocompatible to human pulp fibroblasts and showed upregulation of IL-6 and IL-8 levels.Exposure to childhood adverse events is associated with severe consequences for general health and structural and functional changes in the brain of its survivors. In order to unravel and in the end influence the pathway linking adversity and pathology, neuroimaging research is crucial. Up till now studies in minors are scarce and differ in type of adversity or methodology. Almost all studies report lower cortical thickness, but in a broad variety of regions. In this study we investigated cortical thickness measures and clinical data in a well circumscribed group of adolescents with PTSD related to childhood sexual abuse (CSA) (N = 21) and a healthy non-traumatised control group (N = 21). The ventromedial PFC (vmPFC), ACC, insula, and middle/superior temporal gyrus were chosen as ROI's due to their respective roles in emotion and information processing. No significant effect of group was found for cortical thickness, surface area or volume in any of the ROIs. This is in line with the results of research in adult women with sexual abuse related PTSD, suggesting that this may be specific to this group, independent of age. Recent research points to differential biological and pathological consequences of different types of childhood adversity.Pure intravascular growth of epithelioid hemangioma (EH) is exceptional. Herein, we report a series of 21 intravascular EHs, representing a potential serious diagnostic pitfall by mimicking malignant vascular neoplsms with epithelioid morphology. The tumors developed in 12 males and 4 females, aged from 11 to 71 years (mean age 40.2 years) with a predilection for the extremities (13 of 21, 61.9%), followed by the head and neck (8 of 21, 38.1%). Lesions ranged in size from 2 to 30 mm (mean size 13 mm). The most common presenting feature was a slowly growing nodule. Most neoplasms were solitary (13 of 16 patients, 81.2%) but three patients developed more than one intravascular EH (3 of 16, 18.8%). Treatment consisted of complete surgical excision and was generally curative. Follow-up was available for 13 lesions that had developed in ten patients (range 4-72 months, mean 27.3 months). No recurrences or development of additional tumors were observed. All 21 lesions developed in subcutaneous veins. Two morphologiive by immunohistochemistry (6 out of 6), one out of six cases (case 6) displayed FOSB nuclear positivity in about 30% of the lesional endothelial cells. Eight cases were analysed by FISH for the presence of FOS and FOSB gene rearrangements. While all cases were negative for FOSB rearrangements, a single case proved positive for FOS gene break-apart. In conclusion, intravascular growth of EH is not associated with adverse biological behavior. Solid intravascular proliferations of endothelial cells can mimic a malignant vascular tumor with epithelioid morphology. Nevertheless, intravascular EHs display mild cytological atypia coupled with low mitotic activity, and a lack of atypical mitoses, pronounced nuclear atypia, multilayering or tumor necrosis. Finally, the FOS gene is infrequently rearranged, and there are no FOSB gene abnormalities in this subset of EHs, suggesting a potential distinct pathogenesis than most classic EHs.Diagnosis of osteocartilaginous pathologies depends on morphological examination and immunohistochemical and molecular biology analyses. Decalcification is required before tissue processing, but available protocols often lead to altered proteins and nucleic acids, and thus compromise the diagnosis. The objective of this study was to compare the effect of different methods of decalcification on histomolecular analyses required for diagnosis and to recommend an optimal protocol for processing these samples in routine practice. We prospectively submitted 35 tissue samples to different decalcification procedures with hydrochloric acid, formic acid, and EDTA, in short, overnight and long cycles for 1 to >10 cycles. Preservation of protein integrity was examined by immunohistochemistry, and quality of nucleic acids was estimated after extraction (DNA and RNA concentrations, 260/280 ratios, PCR cycle thresholds), analysis of DNA mutations (high-resolution melting) or amplifications (PCR, in situ hybridization), and detection of fusion transcripts (RT-PCR, in situ hybridization). Hydrochloric acid- and long-term formic acid-based decalcification induced false-negative results on immunohistochemistry and molecular analysis. EDTA and short-term formic acid-based decalcification ( less then 5 cycles of 6 h each) did not alter antigenicity and allowed for detection of gene mutations, amplifications or even fusion transcripts. EDTA showed superiority for in situ hybridization techniques. According to these results and our institutional experience, we propose recommendations for decalcification of bone samples, from biopsies to surgical specimens.Hereditary spastic paraplegia (HSP) is a heterogeneous inherited disorder that manifests with lower extremity weakness and spasticity. HSP can be inherited by autosomal dominant, autosomal recessive, and X-linked inheritance patterns. https://www.selleckchem.com/products/namodenoson-cf-102.html Recent studies have shown that, although rare, mutations in a single gene can lead to multiple patterns of inheritance of HSP. We enrolled the HSP family showing autosomal dominant inheritance and performed genetic study to find the cause of phenotype in this family. We recruited five members of a Korean family as study participants. Four of the five family members had pure HSP. Part of the family members underwent whole-exome sequencing (WES) to identify the causative mutation. As the result of WES and Sanger sequencing analysis, a novel missense mutation (c.452 C > T, p.Ala151Val) of ERLIN2 gene was identified as the cause of the autosomal dominant HSP in the family. Our study suggests that the ERLIN2 gene leads to both autosomal recessive and autosomal dominant patterns of inheritance in HSP.
    Data were analyzed using One-way ANOVA (α  =  0.05). Both the GO-coated NiTi and GO/Ag-coated NiTi alloys showed better corrosion resistance, a lower rate of corrosion, and higher protection efficiency than the bare NiTi alloy. The coated NiTi alloys were biocompatible to human pulp fibroblasts and showed upregulation of IL-6 and IL-8 levels.Exposure to childhood adverse events is associated with severe consequences for general health and structural and functional changes in the brain of its survivors. In order to unravel and in the end influence the pathway linking adversity and pathology, neuroimaging research is crucial. Up till now studies in minors are scarce and differ in type of adversity or methodology. Almost all studies report lower cortical thickness, but in a broad variety of regions. In this study we investigated cortical thickness measures and clinical data in a well circumscribed group of adolescents with PTSD related to childhood sexual abuse (CSA) (N = 21) and a healthy non-traumatised control group (N = 21). The ventromedial PFC (vmPFC), ACC, insula, and middle/superior temporal gyrus were chosen as ROI's due to their respective roles in emotion and information processing. No significant effect of group was found for cortical thickness, surface area or volume in any of the ROIs. This is in line with the results of research in adult women with sexual abuse related PTSD, suggesting that this may be specific to this group, independent of age. Recent research points to differential biological and pathological consequences of different types of childhood adversity.Pure intravascular growth of epithelioid hemangioma (EH) is exceptional. Herein, we report a series of 21 intravascular EHs, representing a potential serious diagnostic pitfall by mimicking malignant vascular neoplsms with epithelioid morphology. The tumors developed in 12 males and 4 females, aged from 11 to 71 years (mean age 40.2 years) with a predilection for the extremities (13 of 21, 61.9%), followed by the head and neck (8 of 21, 38.1%). Lesions ranged in size from 2 to 30 mm (mean size 13 mm). The most common presenting feature was a slowly growing nodule. Most neoplasms were solitary (13 of 16 patients, 81.2%) but three patients developed more than one intravascular EH (3 of 16, 18.8%). Treatment consisted of complete surgical excision and was generally curative. Follow-up was available for 13 lesions that had developed in ten patients (range 4-72 months, mean 27.3 months). No recurrences or development of additional tumors were observed. All 21 lesions developed in subcutaneous veins. Two morphologiive by immunohistochemistry (6 out of 6), one out of six cases (case 6) displayed FOSB nuclear positivity in about 30% of the lesional endothelial cells. Eight cases were analysed by FISH for the presence of FOS and FOSB gene rearrangements. While all cases were negative for FOSB rearrangements, a single case proved positive for FOS gene break-apart. In conclusion, intravascular growth of EH is not associated with adverse biological behavior. Solid intravascular proliferations of endothelial cells can mimic a malignant vascular tumor with epithelioid morphology. Nevertheless, intravascular EHs display mild cytological atypia coupled with low mitotic activity, and a lack of atypical mitoses, pronounced nuclear atypia, multilayering or tumor necrosis. Finally, the FOS gene is infrequently rearranged, and there are no FOSB gene abnormalities in this subset of EHs, suggesting a potential distinct pathogenesis than most classic EHs.Diagnosis of osteocartilaginous pathologies depends on morphological examination and immunohistochemical and molecular biology analyses. Decalcification is required before tissue processing, but available protocols often lead to altered proteins and nucleic acids, and thus compromise the diagnosis. The objective of this study was to compare the effect of different methods of decalcification on histomolecular analyses required for diagnosis and to recommend an optimal protocol for processing these samples in routine practice. We prospectively submitted 35 tissue samples to different decalcification procedures with hydrochloric acid, formic acid, and EDTA, in short, overnight and long cycles for 1 to >10 cycles. Preservation of protein integrity was examined by immunohistochemistry, and quality of nucleic acids was estimated after extraction (DNA and RNA concentrations, 260/280 ratios, PCR cycle thresholds), analysis of DNA mutations (high-resolution melting) or amplifications (PCR, in situ hybridization), and detection of fusion transcripts (RT-PCR, in situ hybridization). Hydrochloric acid- and long-term formic acid-based decalcification induced false-negative results on immunohistochemistry and molecular analysis. EDTA and short-term formic acid-based decalcification ( less then 5 cycles of 6 h each) did not alter antigenicity and allowed for detection of gene mutations, amplifications or even fusion transcripts. EDTA showed superiority for in situ hybridization techniques. According to these results and our institutional experience, we propose recommendations for decalcification of bone samples, from biopsies to surgical specimens.Hereditary spastic paraplegia (HSP) is a heterogeneous inherited disorder that manifests with lower extremity weakness and spasticity. HSP can be inherited by autosomal dominant, autosomal recessive, and X-linked inheritance patterns. https://www.selleckchem.com/products/namodenoson-cf-102.html Recent studies have shown that, although rare, mutations in a single gene can lead to multiple patterns of inheritance of HSP. We enrolled the HSP family showing autosomal dominant inheritance and performed genetic study to find the cause of phenotype in this family. We recruited five members of a Korean family as study participants. Four of the five family members had pure HSP. Part of the family members underwent whole-exome sequencing (WES) to identify the causative mutation. As the result of WES and Sanger sequencing analysis, a novel missense mutation (c.452 C > T, p.Ala151Val) of ERLIN2 gene was identified as the cause of the autosomal dominant HSP in the family. Our study suggests that the ERLIN2 gene leads to both autosomal recessive and autosomal dominant patterns of inheritance in HSP.
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