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9 hrs ago


While youth have varying responses to mass shootings, possibly due to risk and protective factors as well as level of exposure, the mental health outcomes are significant and include posttraumatic stress, suicide, depression, substance abuse, and anxiety. Efforts at developing effective prevention and treatment programs are still underway but generally take a tiered public health approach. Mass shootings have significant mental health outcomes for youth survivors, particularly those with direct exposure or risk factors. Continued efforts are needed to better understand the effects of mass shootings and how to prevent them from occurring as well as how to best address the needs of survivors.
Despite the global increase in the prevalence of autism spectrum disorders (ASD), relevant research studies are lacking in Brunei Darussalam. Various studies have shown a significant association between a lowered 2D4D ratio (ratio of second digit/index finger to the fourth digit/ring finger) and ASD, making it one of the potential phenotypic biomarkers for early detection of autism, which is important for early intervention and management.

The objective of this study is to explore the association between 2D4D ratio and ASD in Brunei Darussalam, as a potential tool to complement early ASD diagnosis.

We conducted a case-control study comprising 28 ASD and 62 typically developing (TD) children in the case and control group, respectively (age range 3-11years old; median age 6yearsold). Median 2D4D ratios were measured, compared and analysed between the two groups. Logistic regression models were used to explore potential associations between the median 2D4D ratio and ASD in respective gender, for both left ts the importance of considering gender-specific biomarkers for ASD diagnosis.
The current American College of Cardiology and American Heart Association (ACC/AHA) guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel for 6months followed by lifelong aspirin after transcatheter aortic valve replacement (TAVR). However, studies that have DAPT with aspirin following TAVR have questioned this recommendation as DAPT has been associated with more bleeding events compared to aspirin. We performed a systematic review and meta-analysis of all the RCTs comparing DAPT (aspirin plus clopidogrel) with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement.

The databases of Embase, PubMed, and Cochrane library were searched from inception to Oct 1, 2020, and randomized controlled trials (RCTs) reporting aspirin plus clopidogrel with aspirin alone as antithrombotic treatment after TAVI were included. Revman 5.3 was used to conduct the analysis.

After screening 152 articles, four studies involving 1086 patients (541 patients in the stroke or myocardial infarction compared with DAPT.
Our systematic review and meta-analysis suggested that aspirin alone could decrease the risk of bleeding and was not associated with higher risk of mortality, stroke or myocardial infarction compared with DAPT.The effects of mental diseases on the employment and working situation can be substantial. They are one of the main reasons for inability to work and reduced earning capacity. Against this background the question arises about suitable occupational reintegration measures for people with severe mental illnesses. In recent years, the principle of supported employment has been internationally shown to be increasingly more successful. In this context mentally ill people are primarily placed at a position of the first employment market and supported on-site by a job coach. This concept is inclusive, individual and evidence based. Despite proven effectiveness, it has so far been insufficiently implemented in German-speaking regions. In the future it will be a matter of considering the individual needs for assistance of mentally ill people more intensively than previously and to respond with functional and in a best-case scenario, multiprofessional and flexible offers.Rivers are one of the major freshwater resources, which provide water for irrigation, domestic, recreational, environmental, and industrial purposes, but they are extremely vulnerable to pollution due to discharge of untreated waste. Establishing the baseline river water quality data is important, so that monitoring changes over time, assessing impacts of particular developmental projects and setting water quality standards for the protection of the river, can be undertaken. In the present study, water quality assessment was done for a segment of Yamuna River passing through Panipat district, Haryana, India. This study is an attempt to know the impact of wastewater generated due to urban and industrial activities taking place in Panipat city and nearby areas, on River Yamuna. https://www.selleckchem.com/products/OSI-930.html Furthermore, vulnerability zone of River Yamuna was delineated using CCME-WQI, NSF-WQI, and hierarchical cluster analysis (HCA). The water quality samples were further evaluated for the agricultural and industrial purposes to determine whether the water can be used for irrigation and industrial requirements. The study also considered the existing land use land cover (LULC) on left and right banks of the River Yamuna and the wastewater carrying drain. River Yamuna travels nearly a distance of ≈ 44 Kms in and around Panipat district and the results of the study indicated that nearly 13 Km stretch of River is more vulnerable to pollution. Thus, it is suggested that wastewater discharge regulation, installation of effluent treatments plants, and maintenance of environmental flow are prerequisite to protect and restore the River Yamuna.
Long non-coding RNA (lncRNA) has been testified to influence the initiation and evolution of sundry carcinomas. Recently, lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been found to display vital regulating functions in various cancers.

qRT-PCR was used to verify the dysregulation of FOXD2-AS1 expression in CCA cells and tissues, and the correlation of FOXD2-AS1 expression with clinicopathological characteristics was investigated. The viability, migration, and invasion of CCA cells were verified through CCK-8 assay, colony formation experiment, wound healing assay, and transwell assay. The regulatory networks of FOXD2-AS1 were analyzed by Bioinformatic prediction and dual-luciferase reporter assay.

We discovered that FOXD2-AS1 was significantly upregulated in CCA and its up-regulation was closely correlated with terminal TNM stage, lymph node metastasis and poor survival in the current research. In addition, it was revealed that FOXD2-AS1 was an independent prognostic factor. Functional tests uncovered that the cell viability, migration, and invasion could be restrained through downregulating the expression of FOXD2-AS1, while FOXD2-AS1 overexpression could facilitate the cell viability, migration, and invasion.

13 hrs ago


RESULTS Of the 40 subjects, 20(50%) each were in the two groups. https://www.selleckchem.com/products/lonafarnib-sch66336.html In Group-A mean age was 42.75±11.13 years. In Group-B, it was 40.50±9.14 years. Eccentric muscle energy technique and static stretching technique both showed significant results (p0.05 each) on all parameters. CONCLUSIONS Both the techniques used were found to be equally effective in decreasing pain, improving cervical range of motion and reducing neck disability.OBJECTIVE To determine the association of single nucleotide polymorphism in three CC, TT and TC genotypes of transforming growth factor β1 T29C in breast cancer patients. METHODS The case-control study was conducted from April 2017 to April 2018 at the Islamic International Medical College, Rawalpindi, Pakistan, in collaboration with Nuclear Oncology Medicine and Radiotherapy Institute and Holy Family Hospital, Rawalpindi. Using convenience sampling, breast cancer cases and healthy controls were enrolled. All investigations were done using standardized laboratory protocols. The outcomes were determined in terms of association of single nucleotide polymorphism of transforming growth factor β1with breast cancer. Data was analysed using SPSS 21. RESULTS Of the 150 subjects, 80(53.3%) were cases and 70(47.7%) were healthy controls. Among the cases, the most frequent genotype was CC 38(47.5%) followed by TC 26(32.5%) and TT 16(20%). Among the controls, the corrsesponding values were 50(71.42%), 13(18.5%) and 7(10%). Transforming growth factor β1 TC genotype was strongly associated with the increased risk of developing breast cancer (odds ratio 3.79). CONCLUSIONS The incidence of breast cancer was markedly lower among women with CC genotype compared to those with CT or TT genotypes.BACKGROUND Esophageal squamous cell carcinoma (ESCC), a major histological subtype of esophageal cancer, is a common cause of tumor-related deaths in the world. Due to the lack of understanding of the pathogenesis of ESCC, its clinical treatment is still a big challenge. In the present study, we aimed to identify an ESCC-related gene in the GEO dataset, and to explore its function and mechanism in ESCC. MATERIAL AND METHODS The GSE dataset (GSE100492) consisting of 10 samples was analyzed using GEO2R for identifying the differentially expressed genes between ESCC and normal samples. Expression levels of mRNA and miRNA in ESCC tissues and cells were detected via quantitative real-time polymerase chain reaction. Protein expression was analyzed by western blot. Cell proliferation viability was determined through MTT and colony formation. Cell distribution and apoptosis was detected by flow cytometry. MiRNA target prediction was analyzed by bioinformatics. The interplay between miR-340-5p and PIK3C3 was validated by dual-luciferase reporter assay. RESULTS PIK3C3 was lowly expressed in ESCC tissue and indicated a poor prognosis in patents. Overexpression of PIK3C3 in vitro repressed cell proliferation of KYSE-150 and TE-12 cells. Moreover, PIK3C3 overexpression was demonstrated to enhance the sensitivity of KYSE-150 and TE-12 cells to irradiation. In addition, miR-340-5p was revealed to directly bind and negatively modulate PIK3C3 expression in ESCC. Blockage of miR-340-5p promoted ESCC cell proliferation, while rescue of PIK3C3 reversed this effect. MiR-340-5p was highly expressed in ESCC tissue and it exhibited a negative correlation with PIK3C3 expression. CONCLUSIONS MiR-340-5p functioned as an oncogene of ESCC by directly binding and repressing the expression of PIK3C3.OBJECTIVE A major challenge in neuroprosthetics is the restoration of sensory-motor hand functions in upper-limb amputees. Neuroprostheses based on the direct re-connection of the peripheral nerves may be an interesting approach for re-establishing the natural and effective bidirectional control of hand prostheses. Recent results have shown that transverse intrafascicular multichannel electrodes (TIMEs) can restore natural and sophisticated sensory feedback. However, the potential of using TIME-recorded motor intraneural signals to decode grasping tasks has not as yet been explored. APPROACH In this study, we show that several hand-movement intentions can be decoded from intraneural signals recorded using four TIMEs implanted in the median and ulnar nerves of an upper limb amputee. Experimental sessions were performed over a week, from day 16 to day 23 after the surgical operation. Intraneural activity was recorded during several hand motor tasks imagined by the subject and processed offline. MAIN RESULTS We obtained a very high decoding accuracy, even when considering 11 class states (up to 83%). Moreover, the stability of the recording using TIMEs was robust and reliable in all sessions as shown by the possibility of using the same TIME channels for decoding over time. These results confirm that neural signals recorded by multichannel intraneural electrodes can be used to decode several movement intentions with high accuracy. SIGNIFICANCE Therefore, TIMEs could be used in the future to achieve a complete bidirectional approach exploiting neural pathways, to make a more natural and intuitive new generation of hand prostheses that have a closer resemblance to a healthy hand. Creative Commons Attribution license.AIMS To investigate the diagnostic performance of quantitative flow ratio (QFR) in assessing the physiological relevance of coronary lesions in the presence of severe aortic valve stenosis (SAS). METHODS AND RESULTS 115 SAS patients (138 coronary arteries) were included. Functional assessment of coronary stenoses was performed with fractional flow reserve (FFR) before transcatheter aortic-valve implantation (TAVI). Subsequently, QFR was calculated at a central core laboratory, blinded to FFR results. The diagnostic yield of QFR was assessed using FFR as reference. Coronary stenoses were intermediate (diameter stenosis 48±10%, FFR 0.84 [0.77-0.89], QFR 0.82 [0.73-0.89]). Per-vessel sensitivity, specificity, area under the ROC curve and accuracy of QFR were 84% (95% CI 71-92%), 80% (95% CI 69-88%), 0.88 (95% CI 0.82-0.93) and 81%, respectively. Diagnostic accuracy of QFR significantly decreased in patients with aortic valve area (AVA) less then 0.60 cm2. Diagnostic performance of QFR was superior to angiography in assessing the FFR-based functional significance (AUC 0.

13 hrs ago


Patients with low IGJ had a 7.2-fold (p<0.001) increase in risk of disease-specific death with a median DSS of 13 months. Low IGJ showed an area under curve (AUC) of 0.89 with 91.0% sensitivity and 87.6% specificity to identify early disease-specific mortality (defined as DSS ≤12 months). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed a global dampening of immune pathways in low IGJ tumors.

Our work showed that IGJ is a robust and independent prognostic biomarker for disease-specific mortality in HPV+ HNSCC. Patient with HPV+ HNSCC with limited adaptive immune functionality should not be candidates for treatment de-escalation modalities.
Our work showed that IGJ is a robust and independent prognostic biomarker for disease-specific mortality in HPV+ HNSCC. Patient with HPV+ HNSCC with limited adaptive immune functionality should not be candidates for treatment de-escalation modalities.Myeloid-derived cells, in particular macrophages, are increasingly recognized as critical regulators of the balance of immunity and tolerance. However, whether they initiate autoimmune disease or perpetuate disease progression in terms of epiphenomena remains undefined.Here, we show that depletion of MCPIP1 in macrophages and granulocytes (Mcpip1fl/fl-LysMcre+ C57BL/6 mice) is sufficient to trigger severe autoimmune disease. This was evidenced by the expansion of B cells and plasma cells and spontaneous production of autoantibodies, including anti-dsDNA, anti-Smith and anti-histone antibodies. Consequently, we document evidence of severe skin inflammation, pneumonitis and histopathologic evidence of glomerular IgG deposits alongside mesangioproliferative nephritis in 6-month-old mice. These phenomena are related to systemic autoinflammation, which secondarily induces a set of cytokines such as Baff, Il5, Il9 and Cd40L, affecting adaptive immune responses. Therefore, abnormal macrophage activation is a key factor involved in the loss of immune tolerance.Overall, we demonstrate that deficiency of MCPIP1 solely in myeloid cells triggers systemic lupus-like autoimmunity and that the control of myeloid cell activation is a crucial checkpoint in the development of systemic autoimmunity.
The balloon-expandable SAPIEN 3 (S3) is superior to the older-generation balloon-expandable SAPIEN XT (XT) in a lower incidence of paravalvular aortic regurgitation, lower complication rates and better survival in transcatheter aortic valve implantation (TAVI). However, prosthesis-patient mismatch (PPM) more frequently occurs in S3 than XT. Further, little information is available on PPM after TAVI using S3 in Asians. This study aims to determine the incidence and predictors of PPM in S3 by focusing on the difference between S3 and XT using data from a Japanese multicentre registry.

From the Optimised transCathEter vAlvular iNtervention-TAVI (OCEAN-TAVI) registry, 2134 patients undergoing TAVI using S3 or XT were included. PPM was defined as moderate if ≧0.65 but ≦0.85 cm
/m
or severe if <0.65 cm
/m
at the indexed effective orifice area by postprocedural echocardiography.

The incidence of moderate and severe PPM in S3 was 13.3% and 1.3%, respectively. The 20 mm transcatheter heart valve (THV) wconsiderable number of patients were treated by the 20 mm S3 in an Asian cohort. The 20 mm THV was identified as a strong predictor for PPM.
To determine the extent to which newborns with neonatal abstinence syndrome (NAS) are concentrated in some hospitals as compared with newborns without NAS and whether care quality and safety differed among these hospitals. We hypothesized that newborns with NAS would be cared for in poorer-quality hospitals.

Secondary analysis of 3 2016 data sets (1) the panel study of effects of changes in nursing on patient outcomes-US survey of hospital registered nurses regarding work conditions and safety, (2) inpatient discharge abstracts, and (3) the American Hospital Association annual survey. Newborns in 266 hospitals from the 4 states where the panel study of effects of changes in nursing on patient outcomes was conducted were included. We used Lorenz curves to determine if newborns with NAS were concentrated in different hospitals than newborns without NAS and whether care quality and safety differed among those hospitals. https://www.selleckchem.com/products/brd3308.html Quality and safety were assessed by staff nurses by using standard survey questions.

Of importance of examining hospital factors.
To examine visitor guidelines among children's hospitals in the United States in response to the coronavirus 2019 (COVID-19) pandemic.

A retrospective assessment of visitor guidelines in 239 children's hospitals in the United States.

In this study, we present an analysis of 239 children's hospital visitor guidelines posted to hospitals' Web sites during 1 week in June 2020. Of the 239 hospitals, only 28 did not have posted guidelines for review. The guidelines were analyzed and grouped by how the guidelines were updated in response to COVID-19. Parental visitation was restricted to 1 parent in 116 of the posted guidelines (49%). There were no obvious similarities among guidelines associated with their geographical (eg, state or local) location. As of February 2021, 33 of 55 (60%) randomly selected hospitals had not changed their visitor policy since our initial review.

The COVID-19 pandemic triggered changes in publicly reported visitor guidelines across the majority of children's hospitals. With our findings, we suggest wide variation in policies and practices in how guidelines were updated. More work is needed to understand how to optimize public safety and preserve family-centered care and parental authority in times of crisis.
The COVID-19 pandemic triggered changes in publicly reported visitor guidelines across the majority of children's hospitals. With our findings, we suggest wide variation in policies and practices in how guidelines were updated. More work is needed to understand how to optimize public safety and preserve family-centered care and parental authority in times of crisis.
Emerging evidence, predominately from European and Asian countries, describes opposing effects of occupational physical activity (OPA) and leisure-time physical activity (LTPA) on cardiovascular health. This analysis examined cardiovascular disease (CVD) prevalence associated with OPA and LTPA.

This cross-sectional analysis of 2015 National Health Interview Survey data (n=16 974) employed logistic regression to estimate odds (OR) of self-reported CVD (coronary heart disease, heart attack, stroke or angina) with self-reported total occupational activity (TOA), occupational exertion (OE), occupational standing and walking (OSW) and LTPA. OPA was measured using two questions 'How often does your job involve…' (1) 'repeated lifting, pushing, pulling or bending?' (OE) and (2) 'standing or walking around?' (OSW) with responses on a 5-item Likert scale (0=never, 4=always). TOA was categorised similarly after summing OE and OSW scores. LTPA was defined as 0, 1-149 or ≥150 min/week of moderate-to-vigorous activity.

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9 hrs ago


While youth have varying responses to mass shootings, possibly due to risk and protective factors as well as level of exposure, the mental health outcomes are significant and include posttraumatic stress, suicide, depression, substance abuse, and anxiety. Efforts at developing effective prevention and treatment programs are still underway but generally take a tiered public health approach. Mass shootings have significant mental health outcomes for youth survivors, particularly those with direct exposure or risk factors. Continued efforts are needed to better understand the effects of mass shootings and how to prevent them from occurring as well as how to best address the needs of survivors.
Despite the global increase in the prevalence of autism spectrum disorders (ASD), relevant research studies are lacking in Brunei Darussalam. Various studies have shown a significant association between a lowered 2D4D ratio (ratio of second digit/index finger to the fourth digit/ring finger) and ASD, making it one of the potential phenotypic biomarkers for early detection of autism, which is important for early intervention and management.

The objective of this study is to explore the association between 2D4D ratio and ASD in Brunei Darussalam, as a potential tool to complement early ASD diagnosis.

We conducted a case-control study comprising 28 ASD and 62 typically developing (TD) children in the case and control group, respectively (age range 3-11years old; median age 6yearsold). Median 2D4D ratios were measured, compared and analysed between the two groups. Logistic regression models were used to explore potential associations between the median 2D4D ratio and ASD in respective gender, for both left ts the importance of considering gender-specific biomarkers for ASD diagnosis.
The current American College of Cardiology and American Heart Association (ACC/AHA) guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel for 6months followed by lifelong aspirin after transcatheter aortic valve replacement (TAVR). However, studies that have DAPT with aspirin following TAVR have questioned this recommendation as DAPT has been associated with more bleeding events compared to aspirin. We performed a systematic review and meta-analysis of all the RCTs comparing DAPT (aspirin plus clopidogrel) with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement.

The databases of Embase, PubMed, and Cochrane library were searched from inception to Oct 1, 2020, and randomized controlled trials (RCTs) reporting aspirin plus clopidogrel with aspirin alone as antithrombotic treatment after TAVI were included. Revman 5.3 was used to conduct the analysis.

After screening 152 articles, four studies involving 1086 patients (541 patients in the stroke or myocardial infarction compared with DAPT.
Our systematic review and meta-analysis suggested that aspirin alone could decrease the risk of bleeding and was not associated with higher risk of mortality, stroke or myocardial infarction compared with DAPT.The effects of mental diseases on the employment and working situation can be substantial. They are one of the main reasons for inability to work and reduced earning capacity. Against this background the question arises about suitable occupational reintegration measures for people with severe mental illnesses. In recent years, the principle of supported employment has been internationally shown to be increasingly more successful. In this context mentally ill people are primarily placed at a position of the first employment market and supported on-site by a job coach. This concept is inclusive, individual and evidence based. Despite proven effectiveness, it has so far been insufficiently implemented in German-speaking regions. In the future it will be a matter of considering the individual needs for assistance of mentally ill people more intensively than previously and to respond with functional and in a best-case scenario, multiprofessional and flexible offers.Rivers are one of the major freshwater resources, which provide water for irrigation, domestic, recreational, environmental, and industrial purposes, but they are extremely vulnerable to pollution due to discharge of untreated waste. Establishing the baseline river water quality data is important, so that monitoring changes over time, assessing impacts of particular developmental projects and setting water quality standards for the protection of the river, can be undertaken. In the present study, water quality assessment was done for a segment of Yamuna River passing through Panipat district, Haryana, India. This study is an attempt to know the impact of wastewater generated due to urban and industrial activities taking place in Panipat city and nearby areas, on River Yamuna. https://www.selleckchem.com/products/OSI-930.html Furthermore, vulnerability zone of River Yamuna was delineated using CCME-WQI, NSF-WQI, and hierarchical cluster analysis (HCA). The water quality samples were further evaluated for the agricultural and industrial purposes to determine whether the water can be used for irrigation and industrial requirements. The study also considered the existing land use land cover (LULC) on left and right banks of the River Yamuna and the wastewater carrying drain. River Yamuna travels nearly a distance of ≈ 44 Kms in and around Panipat district and the results of the study indicated that nearly 13 Km stretch of River is more vulnerable to pollution. Thus, it is suggested that wastewater discharge regulation, installation of effluent treatments plants, and maintenance of environmental flow are prerequisite to protect and restore the River Yamuna.
Long non-coding RNA (lncRNA) has been testified to influence the initiation and evolution of sundry carcinomas. Recently, lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been found to display vital regulating functions in various cancers.

qRT-PCR was used to verify the dysregulation of FOXD2-AS1 expression in CCA cells and tissues, and the correlation of FOXD2-AS1 expression with clinicopathological characteristics was investigated. The viability, migration, and invasion of CCA cells were verified through CCK-8 assay, colony formation experiment, wound healing assay, and transwell assay. The regulatory networks of FOXD2-AS1 were analyzed by Bioinformatic prediction and dual-luciferase reporter assay.

We discovered that FOXD2-AS1 was significantly upregulated in CCA and its up-regulation was closely correlated with terminal TNM stage, lymph node metastasis and poor survival in the current research. In addition, it was revealed that FOXD2-AS1 was an independent prognostic factor. Functional tests uncovered that the cell viability, migration, and invasion could be restrained through downregulating the expression of FOXD2-AS1, while FOXD2-AS1 overexpression could facilitate the cell viability, migration, and invasion.

13 hrs ago


RESULTS Of the 40 subjects, 20(50%) each were in the two groups. https://www.selleckchem.com/products/lonafarnib-sch66336.html In Group-A mean age was 42.75±11.13 years. In Group-B, it was 40.50±9.14 years. Eccentric muscle energy technique and static stretching technique both showed significant results (p0.05 each) on all parameters. CONCLUSIONS Both the techniques used were found to be equally effective in decreasing pain, improving cervical range of motion and reducing neck disability.OBJECTIVE To determine the association of single nucleotide polymorphism in three CC, TT and TC genotypes of transforming growth factor β1 T29C in breast cancer patients. METHODS The case-control study was conducted from April 2017 to April 2018 at the Islamic International Medical College, Rawalpindi, Pakistan, in collaboration with Nuclear Oncology Medicine and Radiotherapy Institute and Holy Family Hospital, Rawalpindi. Using convenience sampling, breast cancer cases and healthy controls were enrolled. All investigations were done using standardized laboratory protocols. The outcomes were determined in terms of association of single nucleotide polymorphism of transforming growth factor β1with breast cancer. Data was analysed using SPSS 21. RESULTS Of the 150 subjects, 80(53.3%) were cases and 70(47.7%) were healthy controls. Among the cases, the most frequent genotype was CC 38(47.5%) followed by TC 26(32.5%) and TT 16(20%). Among the controls, the corrsesponding values were 50(71.42%), 13(18.5%) and 7(10%). Transforming growth factor β1 TC genotype was strongly associated with the increased risk of developing breast cancer (odds ratio 3.79). CONCLUSIONS The incidence of breast cancer was markedly lower among women with CC genotype compared to those with CT or TT genotypes.BACKGROUND Esophageal squamous cell carcinoma (ESCC), a major histological subtype of esophageal cancer, is a common cause of tumor-related deaths in the world. Due to the lack of understanding of the pathogenesis of ESCC, its clinical treatment is still a big challenge. In the present study, we aimed to identify an ESCC-related gene in the GEO dataset, and to explore its function and mechanism in ESCC. MATERIAL AND METHODS The GSE dataset (GSE100492) consisting of 10 samples was analyzed using GEO2R for identifying the differentially expressed genes between ESCC and normal samples. Expression levels of mRNA and miRNA in ESCC tissues and cells were detected via quantitative real-time polymerase chain reaction. Protein expression was analyzed by western blot. Cell proliferation viability was determined through MTT and colony formation. Cell distribution and apoptosis was detected by flow cytometry. MiRNA target prediction was analyzed by bioinformatics. The interplay between miR-340-5p and PIK3C3 was validated by dual-luciferase reporter assay. RESULTS PIK3C3 was lowly expressed in ESCC tissue and indicated a poor prognosis in patents. Overexpression of PIK3C3 in vitro repressed cell proliferation of KYSE-150 and TE-12 cells. Moreover, PIK3C3 overexpression was demonstrated to enhance the sensitivity of KYSE-150 and TE-12 cells to irradiation. In addition, miR-340-5p was revealed to directly bind and negatively modulate PIK3C3 expression in ESCC. Blockage of miR-340-5p promoted ESCC cell proliferation, while rescue of PIK3C3 reversed this effect. MiR-340-5p was highly expressed in ESCC tissue and it exhibited a negative correlation with PIK3C3 expression. CONCLUSIONS MiR-340-5p functioned as an oncogene of ESCC by directly binding and repressing the expression of PIK3C3.OBJECTIVE A major challenge in neuroprosthetics is the restoration of sensory-motor hand functions in upper-limb amputees. Neuroprostheses based on the direct re-connection of the peripheral nerves may be an interesting approach for re-establishing the natural and effective bidirectional control of hand prostheses. Recent results have shown that transverse intrafascicular multichannel electrodes (TIMEs) can restore natural and sophisticated sensory feedback. However, the potential of using TIME-recorded motor intraneural signals to decode grasping tasks has not as yet been explored. APPROACH In this study, we show that several hand-movement intentions can be decoded from intraneural signals recorded using four TIMEs implanted in the median and ulnar nerves of an upper limb amputee. Experimental sessions were performed over a week, from day 16 to day 23 after the surgical operation. Intraneural activity was recorded during several hand motor tasks imagined by the subject and processed offline. MAIN RESULTS We obtained a very high decoding accuracy, even when considering 11 class states (up to 83%). Moreover, the stability of the recording using TIMEs was robust and reliable in all sessions as shown by the possibility of using the same TIME channels for decoding over time. These results confirm that neural signals recorded by multichannel intraneural electrodes can be used to decode several movement intentions with high accuracy. SIGNIFICANCE Therefore, TIMEs could be used in the future to achieve a complete bidirectional approach exploiting neural pathways, to make a more natural and intuitive new generation of hand prostheses that have a closer resemblance to a healthy hand. Creative Commons Attribution license.AIMS To investigate the diagnostic performance of quantitative flow ratio (QFR) in assessing the physiological relevance of coronary lesions in the presence of severe aortic valve stenosis (SAS). METHODS AND RESULTS 115 SAS patients (138 coronary arteries) were included. Functional assessment of coronary stenoses was performed with fractional flow reserve (FFR) before transcatheter aortic-valve implantation (TAVI). Subsequently, QFR was calculated at a central core laboratory, blinded to FFR results. The diagnostic yield of QFR was assessed using FFR as reference. Coronary stenoses were intermediate (diameter stenosis 48±10%, FFR 0.84 [0.77-0.89], QFR 0.82 [0.73-0.89]). Per-vessel sensitivity, specificity, area under the ROC curve and accuracy of QFR were 84% (95% CI 71-92%), 80% (95% CI 69-88%), 0.88 (95% CI 0.82-0.93) and 81%, respectively. Diagnostic accuracy of QFR significantly decreased in patients with aortic valve area (AVA) less then 0.60 cm2. Diagnostic performance of QFR was superior to angiography in assessing the FFR-based functional significance (AUC 0.

13 hrs ago


Patients with low IGJ had a 7.2-fold (p<0.001) increase in risk of disease-specific death with a median DSS of 13 months. Low IGJ showed an area under curve (AUC) of 0.89 with 91.0% sensitivity and 87.6% specificity to identify early disease-specific mortality (defined as DSS ≤12 months). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed a global dampening of immune pathways in low IGJ tumors.

Our work showed that IGJ is a robust and independent prognostic biomarker for disease-specific mortality in HPV+ HNSCC. Patient with HPV+ HNSCC with limited adaptive immune functionality should not be candidates for treatment de-escalation modalities.
Our work showed that IGJ is a robust and independent prognostic biomarker for disease-specific mortality in HPV+ HNSCC. Patient with HPV+ HNSCC with limited adaptive immune functionality should not be candidates for treatment de-escalation modalities.Myeloid-derived cells, in particular macrophages, are increasingly recognized as critical regulators of the balance of immunity and tolerance. However, whether they initiate autoimmune disease or perpetuate disease progression in terms of epiphenomena remains undefined.Here, we show that depletion of MCPIP1 in macrophages and granulocytes (Mcpip1fl/fl-LysMcre+ C57BL/6 mice) is sufficient to trigger severe autoimmune disease. This was evidenced by the expansion of B cells and plasma cells and spontaneous production of autoantibodies, including anti-dsDNA, anti-Smith and anti-histone antibodies. Consequently, we document evidence of severe skin inflammation, pneumonitis and histopathologic evidence of glomerular IgG deposits alongside mesangioproliferative nephritis in 6-month-old mice. These phenomena are related to systemic autoinflammation, which secondarily induces a set of cytokines such as Baff, Il5, Il9 and Cd40L, affecting adaptive immune responses. Therefore, abnormal macrophage activation is a key factor involved in the loss of immune tolerance.Overall, we demonstrate that deficiency of MCPIP1 solely in myeloid cells triggers systemic lupus-like autoimmunity and that the control of myeloid cell activation is a crucial checkpoint in the development of systemic autoimmunity.
The balloon-expandable SAPIEN 3 (S3) is superior to the older-generation balloon-expandable SAPIEN XT (XT) in a lower incidence of paravalvular aortic regurgitation, lower complication rates and better survival in transcatheter aortic valve implantation (TAVI). However, prosthesis-patient mismatch (PPM) more frequently occurs in S3 than XT. Further, little information is available on PPM after TAVI using S3 in Asians. This study aims to determine the incidence and predictors of PPM in S3 by focusing on the difference between S3 and XT using data from a Japanese multicentre registry.

From the Optimised transCathEter vAlvular iNtervention-TAVI (OCEAN-TAVI) registry, 2134 patients undergoing TAVI using S3 or XT were included. PPM was defined as moderate if ≧0.65 but ≦0.85 cm
/m
or severe if <0.65 cm
/m
at the indexed effective orifice area by postprocedural echocardiography.

The incidence of moderate and severe PPM in S3 was 13.3% and 1.3%, respectively. The 20 mm transcatheter heart valve (THV) wconsiderable number of patients were treated by the 20 mm S3 in an Asian cohort. The 20 mm THV was identified as a strong predictor for PPM.
To determine the extent to which newborns with neonatal abstinence syndrome (NAS) are concentrated in some hospitals as compared with newborns without NAS and whether care quality and safety differed among these hospitals. We hypothesized that newborns with NAS would be cared for in poorer-quality hospitals.

Secondary analysis of 3 2016 data sets (1) the panel study of effects of changes in nursing on patient outcomes-US survey of hospital registered nurses regarding work conditions and safety, (2) inpatient discharge abstracts, and (3) the American Hospital Association annual survey. Newborns in 266 hospitals from the 4 states where the panel study of effects of changes in nursing on patient outcomes was conducted were included. We used Lorenz curves to determine if newborns with NAS were concentrated in different hospitals than newborns without NAS and whether care quality and safety differed among those hospitals. https://www.selleckchem.com/products/brd3308.html Quality and safety were assessed by staff nurses by using standard survey questions.

Of importance of examining hospital factors.
To examine visitor guidelines among children's hospitals in the United States in response to the coronavirus 2019 (COVID-19) pandemic.

A retrospective assessment of visitor guidelines in 239 children's hospitals in the United States.

In this study, we present an analysis of 239 children's hospital visitor guidelines posted to hospitals' Web sites during 1 week in June 2020. Of the 239 hospitals, only 28 did not have posted guidelines for review. The guidelines were analyzed and grouped by how the guidelines were updated in response to COVID-19. Parental visitation was restricted to 1 parent in 116 of the posted guidelines (49%). There were no obvious similarities among guidelines associated with their geographical (eg, state or local) location. As of February 2021, 33 of 55 (60%) randomly selected hospitals had not changed their visitor policy since our initial review.

The COVID-19 pandemic triggered changes in publicly reported visitor guidelines across the majority of children's hospitals. With our findings, we suggest wide variation in policies and practices in how guidelines were updated. More work is needed to understand how to optimize public safety and preserve family-centered care and parental authority in times of crisis.
The COVID-19 pandemic triggered changes in publicly reported visitor guidelines across the majority of children's hospitals. With our findings, we suggest wide variation in policies and practices in how guidelines were updated. More work is needed to understand how to optimize public safety and preserve family-centered care and parental authority in times of crisis.
Emerging evidence, predominately from European and Asian countries, describes opposing effects of occupational physical activity (OPA) and leisure-time physical activity (LTPA) on cardiovascular health. This analysis examined cardiovascular disease (CVD) prevalence associated with OPA and LTPA.

This cross-sectional analysis of 2015 National Health Interview Survey data (n=16 974) employed logistic regression to estimate odds (OR) of self-reported CVD (coronary heart disease, heart attack, stroke or angina) with self-reported total occupational activity (TOA), occupational exertion (OE), occupational standing and walking (OSW) and LTPA. OPA was measured using two questions 'How often does your job involve…' (1) 'repeated lifting, pushing, pulling or bending?' (OE) and (2) 'standing or walking around?' (OSW) with responses on a 5-item Likert scale (0=never, 4=always). TOA was categorised similarly after summing OE and OSW scores. LTPA was defined as 0, 1-149 or ≥150 min/week of moderate-to-vigorous activity.

13 hrs ago


Prevention is better than cure. A milestone of the anthropocene is the emergence of a series of epidemics and pandemics often characterized by the transmission of a pathogen from animals to human in the past two decades. In particular, the coronavirus disease 2019 (COVID-19) has made a profound impact on emergency responding and policy-making in a public health crisis. Classical solutions for controlling the virus, such as travel restrictions, lockdowns, repurposed drugs and vaccines, are socially unpopular and medically limited by the fast mutation and adaptation of the virus. This is exacerbated by microbial resistance to therapeutic drugs and the slowness of vaccine development. In other words, microbial pathogens are somehow 'smarter' and faster than us, thus calling for more intelligent cures to combat future pandemics. Here, we compare therapeutics for COVID-19 such as synthetic drugs, vaccines, antibodies and phages. We present the strength and limitations of antibiotic and antiviral drugs, vaccines, and antibody-based therapeutics. https://www.selleckchem.com/products/td139.html We describe smarter, cheaper and preventive cures such as bacteriophages, food medicine using probiotics and prebiotics, sports, healthy diet, music, yoga, Tai Chi, dance, reading, knitting, cooking and outdoor activities. Some of these preventive cures have been intuitively developed since thousands of years ago, as illustrated by the fascinating similarity of the Chinese characters for 'music' and 'herbal medicine.'In April 1989, the UK Prime Minister, Margaret Thatcher, convened a full cabinet meeting on climate change addressed by leading scientists. The presentation on mitigation of carbon dioxide emissions was made by the Head of the Energy Technology Support Unit (ETSU), Ken Currie, and identified the key potential options for mitigation by 2020. In this paper, we compare the mitigation potential identified for each proposed option with the 2019 outturn. The largest mitigation options identified were improved end use energy efficiency across the economy and the generation and use of low carbon electricity. Our analysis finds that these have been the key options adopted. Reductions in primary energy use, resulting from improvements in energy efficiency were concentrated in the period 2005-2012 which in 1989 were widely considered to be ambitious. Decarbonisation of electricity has been achieved by the displacement of coal, initially by gas and more recently by renewable electricity. Renewable electricity has exceeded 1989 expectations in the last 5 years and is now the biggest source of CO2 reductions from electricity generation. The contribution envisaged by nuclear electricity has not occurred, largely due its failure to compete in liberalised generation markets. In all cases, the policy environment has been important. We draw lessons for mitigation options to achieve the goal of net zero emissions in the next 30 years. The contribution of demand side and other modular options will remain crucial, as mass-produced technologies tend to improve more quickly than those requiring large construction projects. Environmental, social and political factors will be important, so analysis should not be a purely techno-economic assessment.Current research shows that children with sensory processing (SP) difficulties have limited participation and enjoyment in their daily activities at school. The aim of this study was to explore the prevalence of SP difficulties among Danish children and to explore possible associated factors. Since SP difficulties can affect children's prerequisites for participation in school activities and learning possibilities, this study focused on primary school children. Method. The study was designed as a cross-sectional survey. The sample consisted of 1723 children age 5 to 11 years, who were attending Danish public school (45.5% girls, 53.2% boys). The parents or caregivers of the child completed a Short Sensory Profile (SSP) questionnaire and a demographic questionnaire. One-way ANOVA was used to examine differences between girls and boys regarding sports, geographic area, and parental level of education. Chi-square analysis was used to explore the relationship between sex and SPP scores in the different behavioralnt interventions such as sensory integration through occupational therapy to help children with SP difficulties, in order to improve their ability to participate and learn from school activities.
This study is aimed at validating the A-ONE scale in an Italian population with Central Nervous System (CNS) dysfunction.
. Between May and November 2018, people aged between 60 and 90 with CNS dysfunction were recruited in a hospital in Rome, Italy. Patients were observed and evaluated during the activities of daily living. Internal consistency and reliability were evaluated with Cronbach's coefficient alpha and intraclass correlation coefficient, respectively. As measured with Pearson's correlation coefficient, the validity was examined comparing results of the A-ONE with the Barthel index. Responsiveness was evaluated 30 days after the first administration.

A total of 70 people having a diagnosis of neurological disorders were evaluated. The internal consistency showed Cronbach's coefficient alpha ranging from 0.634 to 0.959. The measurement of reliability varied from 0.984 to 0.997 for intrarater and from 0.979 to 0.998 for interrater. Pearson's correlation coefficient between the A-ONE and the Barthel index and the responsiveness showed statistically significant values (
< 0.01).

The present study provides preliminary evidence of reliability, validity, and responsiveness of the A-ONE when using elderly people with CNS dysfunction.
The present study provides preliminary evidence of reliability, validity, and responsiveness of the A-ONE when using elderly people with CNS dysfunction.
The prevalence of coronary artery disease (CAD) detected in preoperative work-up for transcatheter aortic valve implantation (TAVI) is high. Instead, the management of a concomitant CAD remains unclear. We evaluate the impact of CAD and percutaneous coronary intervention (PCI) on TAVI procedures.

A retrospective study was conducted on 1336 consecutive patients who underwent TAVI in Toulouse University Hospital, Rangueil, France. The studied population was divided into 2 groups CAD-TAVI group and No CAD-TAVI group. Then, the CAD-TAVI group was segregated into 2 subgroups PCI-TAVI group and No PCI-TAVI group. In-hospital adverse clinical outcomes were assessed in each group.

Pre-TAVI work-up revealed significant CAD in 36% of 1030 patients eligible for inclusion in the study. The overall prevalence of in-hospital death, stroke, major or life-threatening bleeding, minor bleeding, major vascular complications, minor vascular complications, pacemaker implantation, and acute kidney injury was 2.7%, 2.4%, 2.8%, 3.

15 hrs ago


Inhibition of Poly(ADP-ribose) polymerase (PARP) is effective for breast cancer susceptibility genes 1 (BRCA1)-deficient breast cancers. Although hormones play critical roles on the occurrence as well as being used in conventional therapies of breast cancer, their impacts on PARP-targeted therapy have been poorly addressed. Here, we showed that addition of estrogen could enhance the cytotoxicity of PARP inhibitors on estrogen receptor (ER)-positive breast cancer cells, causing significant suppression of cell growth. Further analysis revealed that the impact was due to estrogen's stimulating the production of nitric oxide (NO), which could be abrogated when blocking NO formation. Moreover, the effect of estrogen can be resembled by two exogenous nitric oxide donors (SNAP and GSNO). https://www.selleckchem.com/products/sr59230a.html Using ER-negative cell line MDA-MB231, estrogen could not enhance the cell killing of PARP inhibitors any more, but addition of NO donors re-established the enhancing effects. The increased NO level led to accumulation of DNA double strand breaks (DSBs) based on the formation of H2AX foci. Consistent with earlier studies, we demonstrated that NO suppressed the expression of BRCA1, a key player involved in DSB recombination repair. Taken together, these data reveal an important role of estrogen on the treatment of PARP inhibitors, which may affect its clinical treatment and should be considered in precision therapies for ER-positive and negative cancers.Medicinal or herbal plants are widely used for their many favourable properties and are generally safe without any side effects. Saponins are sugar conjugated natural compounds which possess a multitude of biological activities such as medicinal properties, antimicrobial activity, antiviral activity, etc. Saponin production is a part of the normal growth and development process in a lot of plants and plant extracts such as liquorice and ginseng which are exploited as potential drug sources. Herbal compounds have shown a great potential against a wide variety of infectious agents, including viruses such as the SARS-CoV; these are all-natural products and do not show any adverse side effects. This article reviews the various aspects of saponin biosynthesis and extraction, the need for their integration into more mainstream medicinal therapies and how they could be potentially useful in treating viral diseases such as COVID-19, HIV, HSV, rotavirus etc. The literature presents a close review on the saponin efficacy in targeting mentioned viral diseases that occupy a high mortality rate worldwide. This manuscript indicates the role of saponins as a source of dynamic plant based anti-viral remedies and their various methods for extraction from different sources.
Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce cardiac injury and inflammation in patients undergoing diverse cardiac invasive and surgical procedures. However, it is unclear whether RIPC has protective effects in patients undergoing the transfemoral- transcatheter aortic valve implantation (TF-TAVΙ) procedure.

Between September 2013 and September 2015, 55 random consecutive patients were prospectively assigned to receive SHAM preconditioning (SHAM, 22 patients) or Remote Ischemic Preconditioning (RIPC) (4 cycles of 5min intermittent leg ischemia and 5min reperfusion, 33 patients) prior to TF-TAVI. The primary endpoint was to determine the serum levels of hs-cTn-I (necrosis), CK-18 (apoptosis), and IL-1b (inflammation). Quantification was performed using commercially available ELISA kits. Patients were sampled 1-day pre TF-TAVΙ and 24-hours post TF-TAVΙ. Secondary endpoints included total mortality, incidence of periprocedural clinical acute myocardial infarction (AMI), acute kidney injury (AKI), and stroke.

22 SHAM patients and 33 RIPC patients were finally analyzed. Our data revealed no significant difference in serum levels of hs-cTn-I and CK-18 among various groups. However, in the RIPC group, the increase in IL1b level was significantly lower for 24-h post TF-TAVΙ, (p<0.01). There were no significant differences between groups in the secondary endpoints at the follow-up interval of one month. RIPC-related adverse events were not observed.

Our data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in the RIPC group.
Our data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in the RIPC group.
Paravalvular leak (PVL) is a common complication following valve replacement, which leads to heart failure and hemolysis. Transcatheter PVL closure has emerged as a reliable alternative with promising results. We quote the combined three-center experience of PVL patients treated percutaneously.

Consecutive patients treated percutaneously for PVL were retrospectively studied. Procedural characteristics, inhospital, and long-term clinical outcomes were assessed. Technical (successful deployment) and clinical (NYHA and/or hemolysis improvement) success were evaluated.

In total, 39 patients treated for PVL in either the aortic (12 patients) or the mitral (27 patients) position were studied. Amplatzer Vascular Plug III was the most commonly used device among the 45 devices totally implanted. Postprocedurally, the rates of at least moderate PVL (87.5% preprocedurally vs 10.5% at discharge) and functional status (mean NYHA class 2.8±0.7 on admission vs 1.5±0.8 at follow-up) were statistically significantly improved. Total population technical success rate was 89.7%, being comparable between patients treated for mitral or aortic valve PVLs (92.6% vs 83.3%, respectively). Clinical success was achieved in 82.1% of patient cohort without statistical difference among those with isolated aortic or mitral PVL or among those with PVL closure an indication of heart failure or hemolysis. During a mean follow-up of 33.5months, five patients died, including one periprocedural death.

This multicenter recorded experience confirms that percutaneous PVL closure can be performed with high technical and clinical success rates and limited complications that lead to significant PVL reduction and functional status improvement.
This multicenter recorded experience confirms that percutaneous PVL closure can be performed with high technical and clinical success rates and limited complications that lead to significant PVL reduction and functional status improvement.