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  • Level III-retrospective cohort study.
    Level III-retrospective cohort study.
    Whether to preserve or sacrifice the intercostobrachial nerves (ICBN) is a controversial issue. In this trial, we aim to assess the effects of preservation of the ICBN during axillary dissection for patients with breast cancer in terms of pain score immediately postoperatively and several hours later, need for simple analgesia and narcotics, numbness and arm swelling.

    This is a single-institution, single-surgeon randomized controlled trial where a sample of 48 patients with breast cancer, of various age groups, were allocated randomly to any of the 2; preservation or sacrifice categories. Postoperatively, patients were asked by a physician to fill a predesigned questionnaire to assess the studied items during hospitalization and after discharge.

    Among the 48 included patients, ICBN was sacrificed in 24 patients; of which 18 patients (75%) developed numbness in the inner aspect of the arm. While in the ICBN preservation group (24 patients) only 6 patients suffered numbness (25%) with a significant P-valudissecting the axilla properly without injuring these ICBN.
    One of the most common pediatric fractures is a midshaft both bone forearm fracture. The preferred nonoperative treatment is cast immobilization for 6 to 8 weeks; however, 4% to 8% refracture within 6 months. There are no comparative studies evaluating the efficacy of bracing after cast immobilization. We hypothesized that children treated with prolonged functional bracing would have a lower rate of refracture than casting alone or short-term bracing.

    This is a retrospective review of children younger than 15 years of age treated nonoperatively following radius and ulnar shaft fractures treated at 3 tertiary pediatric hospitals. We excluded distal radius/ulna fractures, isolated fractures of the radius/ulna, and fractures near the elbow. Logistic regression analysis on casting plus functional bracing was run to determine if age, translation, or the number of days in brace were associated with refracture. The incidence of refracture was compared between groups.

    A total of 1549 patients were screened and arison study of its kind.
    This is the first level III retrospective comparison study of its kind.
    Synthetic casting materials have been used as alternatives to plaster of Paris (POP) in the treatment of clubfoot using the Ponseti method. The aim of this study was to evaluate the clinical outcome of children with idiopathic clubfoot managed by the Ponseti method using POP versus semirigid fiberglass (SRF).

    Medical records were retrospectively reviewed for all newborns with idiopathic clubfoot who underwent manipulation and casting by the Ponseti technique between January 2013 and December 2016 at 2 different institutions. In all, 136 consecutive clubfeet were included, of which 68 underwent casting with POP (Group A), and 68 were casted using SRF (Group B). Statistical analysis was performed using the Fisher exact test for categorical variables, and the unpaired t test for quantitative parameters.

    Mean age at time of first cast was 10 days (range, 3 to 21 d). Mean Pirani score at start of treatment was 4.6 and 4.5 in Groups A and B, respectively. Mean number of casts for each patient in Group A was 5.2 against 4.2 in patients in Group B. Mean follow-up was 63.8 months (range, 42 to 88 mo). In each group, 4 cases of relapse were reported (2.9%). No complications related to cast phase or brace phase were recorded. Shorter duration of cast treatment was recorded in Group B.

    Despite its higher cost and slightly lower moldability, the use of SRF in experienced hands showed comparable results in idiopathic clubfeet treated by the Ponseti technique.

    Level III.
    Level III.
    The complex syndactyly in Apert syndrome hands is challenging to operate. The synostosis and tightness of skin between third and fourth digits lead to severe coverage problems during ray release. A soft tissue distractor can simplify the release with the aim to keep all 10 fingers.

    A retrospective follow-up of 12 patients/24 hands, median age 8 years (6 to 17 y), 6 boys and 6 girls, operated between 2000 and 2013 was done from 2015 to 2016. The surgical management started with syndactyly release of the first and fourth web, and later of the second. The third stage was placing a soft tissue distractor on the third and fourth finger after osteotomy on the synostosis between them. Four weeks of distraction and 2 weeks of rest resulted in regenerated skin between the digits giving **** better coverage of the released digits at time of separation 6 weeks later. Assessment of hand function, grip strength and completion of the Patient Reported Outcome Measure CHEQ was performed.

    Soft tissue coverage at the time of digit separation was considerably facilitated. We experienced 2 infections in 2 hands. In 18/24 hands median 2 (1 to 3) small full thickness skin grafts were needed, usually for coverage of the base of the digits. All wounds healed well. The children managed different practical tasks well, alternating between best functioning grip depending on the activity. According to CHEQ, the children did median 19 (13 to 27) activities independently and median 8 (2 to 15) nonindependently, of a total of 29. Peak strength values for 10/12 children were for the right hand median 17.8% (9.6% to 40.6%) of normative data and for left hand median 13.6% (2.4% to 20.5%) of normative data.

    Soft tissue distraction facilitates the treatment of acrocephalosyndactyly hands, giving 5-fingered hands. Apert children manage many activities independently but struggled with fine motor skills demanding strength.

    Level IV evidence.
    Level IV evidence.
    Amniotic band syndrome (ABS) is a congenital disorder resulting in fibrous bands that can cause limb anomalies, amputations, and deformities. Clubfoot has been reported in up to 50% of patients with ABS. https://www.selleckchem.com/products/simnotrelvir.html The purpose of this study is to compare treatment characteristics and outcomes of clubfoot patients with ABS to those with idiopathic clubfoot treated with the Ponseti method.

    An Institution Review Board (IRB) approved retrospective review of prospectively gathered data was performed at a single pediatric hospital over a 20-year period. Patients with either idiopathic clubfeet or clubfeet associated with concomitant ABS who were <1 year of age and treated by the Ponseti method were included. Initial Dimeglio score, number of casts, need for heel cord tenotomy, recurrence, and need for further surgery were recorded. Outcomes were classified as "good" (plantigrade foot±heel cord tenotomy), "fair" (need for a limited procedure), or "poor" (need for a full posteromedial release).

    Forty-three clubfeet in 32 patients with ABS, and 320 idiopathic clubfeet in 215 patients were identified.
    Level III-retrospective cohort study. Level III-retrospective cohort study. Whether to preserve or sacrifice the intercostobrachial nerves (ICBN) is a controversial issue. In this trial, we aim to assess the effects of preservation of the ICBN during axillary dissection for patients with breast cancer in terms of pain score immediately postoperatively and several hours later, need for simple analgesia and narcotics, numbness and arm swelling. This is a single-institution, single-surgeon randomized controlled trial where a sample of 48 patients with breast cancer, of various age groups, were allocated randomly to any of the 2; preservation or sacrifice categories. Postoperatively, patients were asked by a physician to fill a predesigned questionnaire to assess the studied items during hospitalization and after discharge. Among the 48 included patients, ICBN was sacrificed in 24 patients; of which 18 patients (75%) developed numbness in the inner aspect of the arm. While in the ICBN preservation group (24 patients) only 6 patients suffered numbness (25%) with a significant P-valudissecting the axilla properly without injuring these ICBN. One of the most common pediatric fractures is a midshaft both bone forearm fracture. The preferred nonoperative treatment is cast immobilization for 6 to 8 weeks; however, 4% to 8% refracture within 6 months. There are no comparative studies evaluating the efficacy of bracing after cast immobilization. We hypothesized that children treated with prolonged functional bracing would have a lower rate of refracture than casting alone or short-term bracing. This is a retrospective review of children younger than 15 years of age treated nonoperatively following radius and ulnar shaft fractures treated at 3 tertiary pediatric hospitals. We excluded distal radius/ulna fractures, isolated fractures of the radius/ulna, and fractures near the elbow. Logistic regression analysis on casting plus functional bracing was run to determine if age, translation, or the number of days in brace were associated with refracture. The incidence of refracture was compared between groups. A total of 1549 patients were screened and arison study of its kind. This is the first level III retrospective comparison study of its kind. Synthetic casting materials have been used as alternatives to plaster of Paris (POP) in the treatment of clubfoot using the Ponseti method. The aim of this study was to evaluate the clinical outcome of children with idiopathic clubfoot managed by the Ponseti method using POP versus semirigid fiberglass (SRF). Medical records were retrospectively reviewed for all newborns with idiopathic clubfoot who underwent manipulation and casting by the Ponseti technique between January 2013 and December 2016 at 2 different institutions. In all, 136 consecutive clubfeet were included, of which 68 underwent casting with POP (Group A), and 68 were casted using SRF (Group B). Statistical analysis was performed using the Fisher exact test for categorical variables, and the unpaired t test for quantitative parameters. Mean age at time of first cast was 10 days (range, 3 to 21 d). Mean Pirani score at start of treatment was 4.6 and 4.5 in Groups A and B, respectively. Mean number of casts for each patient in Group A was 5.2 against 4.2 in patients in Group B. Mean follow-up was 63.8 months (range, 42 to 88 mo). In each group, 4 cases of relapse were reported (2.9%). No complications related to cast phase or brace phase were recorded. Shorter duration of cast treatment was recorded in Group B. Despite its higher cost and slightly lower moldability, the use of SRF in experienced hands showed comparable results in idiopathic clubfeet treated by the Ponseti technique. Level III. Level III. The complex syndactyly in Apert syndrome hands is challenging to operate. The synostosis and tightness of skin between third and fourth digits lead to severe coverage problems during ray release. A soft tissue distractor can simplify the release with the aim to keep all 10 fingers. A retrospective follow-up of 12 patients/24 hands, median age 8 years (6 to 17 y), 6 boys and 6 girls, operated between 2000 and 2013 was done from 2015 to 2016. The surgical management started with syndactyly release of the first and fourth web, and later of the second. The third stage was placing a soft tissue distractor on the third and fourth finger after osteotomy on the synostosis between them. Four weeks of distraction and 2 weeks of rest resulted in regenerated skin between the digits giving much better coverage of the released digits at time of separation 6 weeks later. Assessment of hand function, grip strength and completion of the Patient Reported Outcome Measure CHEQ was performed. Soft tissue coverage at the time of digit separation was considerably facilitated. We experienced 2 infections in 2 hands. In 18/24 hands median 2 (1 to 3) small full thickness skin grafts were needed, usually for coverage of the base of the digits. All wounds healed well. The children managed different practical tasks well, alternating between best functioning grip depending on the activity. According to CHEQ, the children did median 19 (13 to 27) activities independently and median 8 (2 to 15) nonindependently, of a total of 29. Peak strength values for 10/12 children were for the right hand median 17.8% (9.6% to 40.6%) of normative data and for left hand median 13.6% (2.4% to 20.5%) of normative data. Soft tissue distraction facilitates the treatment of acrocephalosyndactyly hands, giving 5-fingered hands. Apert children manage many activities independently but struggled with fine motor skills demanding strength. Level IV evidence. Level IV evidence. Amniotic band syndrome (ABS) is a congenital disorder resulting in fibrous bands that can cause limb anomalies, amputations, and deformities. Clubfoot has been reported in up to 50% of patients with ABS. https://www.selleckchem.com/products/simnotrelvir.html The purpose of this study is to compare treatment characteristics and outcomes of clubfoot patients with ABS to those with idiopathic clubfoot treated with the Ponseti method. An Institution Review Board (IRB) approved retrospective review of prospectively gathered data was performed at a single pediatric hospital over a 20-year period. Patients with either idiopathic clubfeet or clubfeet associated with concomitant ABS who were <1 year of age and treated by the Ponseti method were included. Initial Dimeglio score, number of casts, need for heel cord tenotomy, recurrence, and need for further surgery were recorded. Outcomes were classified as "good" (plantigrade foot±heel cord tenotomy), "fair" (need for a limited procedure), or "poor" (need for a full posteromedial release). Forty-three clubfeet in 32 patients with ABS, and 320 idiopathic clubfeet in 215 patients were identified.
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  • Microalgae have shown great potential as a source of biofuels, food, and other bioproducts. More recently, microfluidic devices have been employed in microalgae-related studies. https://www.selleckchem.com/products/methylene-blue-trihydrate.html However, at small fluid volumes, the options for controlling flow conditions are more limited and mixing becomes largely reliant on diffusion. In this study, we fabricated magnetic artificial cilia (MAC) and implemented them in millimeter scale culture wells and conducted growth experiments with Scenedesmus subspicatus while actuating the ****in a rotating magnetic field to create flow and mixing. In addition, surface of ****was made hydrophilic using plasma treatment and its effect on growth was compared with untreated, hydrophobic MAC. The experiments showed that the growth was enhanced by ten and two times with hydrophobic and hydrophilic MAC, respectively, compared with control groups which contain no MAC. This technique can be used to investigate mixing and flow in small sample volumes, and the enhancement in growth can be beneficial for the throughput of screening studies. Moreover, the methods used for creating and controlling ****can be easily adopted in labs without microfabrication infrastructures, and they can be mastered by people with little prior experience in microfluidics.
    To compare the mental health and neurodevelopmental profiles of school-age children born very preterm, with and without an anxiety disorder, and to identify neonatal medical, psychosocial, and concurrent neurodevelopmental correlates.

    A regional cohort of 102 (51 males, 51 females) children born very preterm (mean [SD] gestation at birth=28wks [2], range=23-31wks) was studied from birth to age 9years alongside a comparison group of 109 (58 males, 51 females) children born at term (mean [SD] gestation at birth=40wks [1], range=38-41wks). At age 9years, all children underwent a neurodevelopmental evaluation while parents were interviewed using the Development and Well-Being Assessment to diagnose a range of DSM-IV childhood psychiatric disorders. Detailed information was also available about the children's neonatal medical course and postnatal psychosocial environment, including maternal mental health and parenting.

    At age 9 years, 21% (n=21) of very preterm and 13% (n=14) of term-born children met diagnogh-risk population.Sexual selection is often thought to promote speciation. This expectation is largely driven by the fact that sexually selected traits can influence mating patterns and contribute to reproductive isolation. Indeed, some comparative studies have shown that clades with sexually selected traits have increased rates of speciation and diversification. However, these studies have almost exclusively focused on one mechanism of sexual selection female choice. Another widespread mechanism is male-male competition. Few empirical studies (if any) have investigated the role of this alternative mechanism in driving diversification. Nevertheless, recent reviews have suggested that male-male competition can increase speciation rates. Here, we investigated whether traits associated with precopulatory male-male competition (i.e., sexually selected weapons) have promoted speciation and diversification in insects. We focused on three clades with both weapons and suitable phylogenies leaf-footed and broad-headed bugs (Coreidae+Alydidae; ∼2850 species), stick insects and relatives (Phasmatodea; ∼3284 species), and scarab beetles (Scarabaeoidea; ∼39,717 species). We found no evidence that weapon-bearing lineages in these clades have higher rates of speciation or diversification than their weaponless relatives. Thus, our results suggest that precopulatory male-male competition may not have strong, general effects on speciation and diversification in insects, a group encompassing ∼60% of all described species.The sodium-dependent phosphate transporters Pit 1 and Pit 2 belong to the solute carrier 20 (SLC20) family of membrane proteins. They are ubiquitously distributed in the human body. Their crucial function is the intracellular transport of inorganic phosphate (Pi) in the form of H2 PO4 - . They are one of the main elements in maintaining physiological phosphate homeostasis. Recent data have emerged that indicate novel roles of Pit 1 and Pit 2 proteins besides the well-known function of Pi transporters. These membrane proteins are believed to be precise phosphate sensors that mediate Pi-dependent intracellular signaling. They are also involved in insulin signaling and influence cellular insulin sensitivity. In diseases that are associated with hyperphosphatemia, such as diabetes and chronic kidney disease (CKD), disturbances in the function of Pit 1 and Pit 2 are observed. Phosphate transporters from the SLC20 family participate in the calcification of soft tissues, mainly blood vessels, during the course of CKD. The glomerulus and podocytes therein can also be a target of pathological calcification that damages these structures. A few studies have demonstrated the development of Pi-dependent podocyte injury that is mediated by Pit 1 and Pit 2. This paper discusses the role of Pit 1 and Pit 2 proteins in podocyte function, mainly in the context of the development of pathological calcification that disrupts permeability of the renal filtration barrier. We also describe the mechanisms that may contribute to podocyte damage by Pit 1 and Pit 2.Increasing demands for protein-based therapeutics such as monoclonal antibodies, fusion proteins, bispecific molecules, and antibody fragments require researchers to constantly find innovative solutions. To increase yields and decrease costs of next generation bioprocesses, highly concentrated cell culture media formulations are developed but often limited by the low solubility of amino acids such as tyrosine, cystine, leucine, and isoleucine, in particular at physiological pH. This study sought to investigate highly soluble and bioavailable derivatives of leucine and isoleucine that are applicable for fed-batch processes. N-lactoyl-leucine and N-lactoyl-isoleucine sodium salts were tested in cell culture media and proved to be beneficial to increase the overall solubility of cell culture media formulations. These modified amino acids proved to be bioavailable for various Chinese hamster ovary (CHO) cells and were suitable for replacement of canonical amino acids in cell culture feeds. The quality of the final recombinant protein was studied in bioprocesses using the derivatives, and the mechanism of cleavage was investigated in CHO cells.
    Microalgae have shown great potential as a source of biofuels, food, and other bioproducts. More recently, microfluidic devices have been employed in microalgae-related studies. https://www.selleckchem.com/products/methylene-blue-trihydrate.html However, at small fluid volumes, the options for controlling flow conditions are more limited and mixing becomes largely reliant on diffusion. In this study, we fabricated magnetic artificial cilia (MAC) and implemented them in millimeter scale culture wells and conducted growth experiments with Scenedesmus subspicatus while actuating the MAC in a rotating magnetic field to create flow and mixing. In addition, surface of MAC was made hydrophilic using plasma treatment and its effect on growth was compared with untreated, hydrophobic MAC. The experiments showed that the growth was enhanced by ten and two times with hydrophobic and hydrophilic MAC, respectively, compared with control groups which contain no MAC. This technique can be used to investigate mixing and flow in small sample volumes, and the enhancement in growth can be beneficial for the throughput of screening studies. Moreover, the methods used for creating and controlling MAC can be easily adopted in labs without microfabrication infrastructures, and they can be mastered by people with little prior experience in microfluidics. To compare the mental health and neurodevelopmental profiles of school-age children born very preterm, with and without an anxiety disorder, and to identify neonatal medical, psychosocial, and concurrent neurodevelopmental correlates. A regional cohort of 102 (51 males, 51 females) children born very preterm (mean [SD] gestation at birth=28wks [2], range=23-31wks) was studied from birth to age 9years alongside a comparison group of 109 (58 males, 51 females) children born at term (mean [SD] gestation at birth=40wks [1], range=38-41wks). At age 9years, all children underwent a neurodevelopmental evaluation while parents were interviewed using the Development and Well-Being Assessment to diagnose a range of DSM-IV childhood psychiatric disorders. Detailed information was also available about the children's neonatal medical course and postnatal psychosocial environment, including maternal mental health and parenting. At age 9 years, 21% (n=21) of very preterm and 13% (n=14) of term-born children met diagnogh-risk population.Sexual selection is often thought to promote speciation. This expectation is largely driven by the fact that sexually selected traits can influence mating patterns and contribute to reproductive isolation. Indeed, some comparative studies have shown that clades with sexually selected traits have increased rates of speciation and diversification. However, these studies have almost exclusively focused on one mechanism of sexual selection female choice. Another widespread mechanism is male-male competition. Few empirical studies (if any) have investigated the role of this alternative mechanism in driving diversification. Nevertheless, recent reviews have suggested that male-male competition can increase speciation rates. Here, we investigated whether traits associated with precopulatory male-male competition (i.e., sexually selected weapons) have promoted speciation and diversification in insects. We focused on three clades with both weapons and suitable phylogenies leaf-footed and broad-headed bugs (Coreidae+Alydidae; ∼2850 species), stick insects and relatives (Phasmatodea; ∼3284 species), and scarab beetles (Scarabaeoidea; ∼39,717 species). We found no evidence that weapon-bearing lineages in these clades have higher rates of speciation or diversification than their weaponless relatives. Thus, our results suggest that precopulatory male-male competition may not have strong, general effects on speciation and diversification in insects, a group encompassing ∼60% of all described species.The sodium-dependent phosphate transporters Pit 1 and Pit 2 belong to the solute carrier 20 (SLC20) family of membrane proteins. They are ubiquitously distributed in the human body. Their crucial function is the intracellular transport of inorganic phosphate (Pi) in the form of H2 PO4 - . They are one of the main elements in maintaining physiological phosphate homeostasis. Recent data have emerged that indicate novel roles of Pit 1 and Pit 2 proteins besides the well-known function of Pi transporters. These membrane proteins are believed to be precise phosphate sensors that mediate Pi-dependent intracellular signaling. They are also involved in insulin signaling and influence cellular insulin sensitivity. In diseases that are associated with hyperphosphatemia, such as diabetes and chronic kidney disease (CKD), disturbances in the function of Pit 1 and Pit 2 are observed. Phosphate transporters from the SLC20 family participate in the calcification of soft tissues, mainly blood vessels, during the course of CKD. The glomerulus and podocytes therein can also be a target of pathological calcification that damages these structures. A few studies have demonstrated the development of Pi-dependent podocyte injury that is mediated by Pit 1 and Pit 2. This paper discusses the role of Pit 1 and Pit 2 proteins in podocyte function, mainly in the context of the development of pathological calcification that disrupts permeability of the renal filtration barrier. We also describe the mechanisms that may contribute to podocyte damage by Pit 1 and Pit 2.Increasing demands for protein-based therapeutics such as monoclonal antibodies, fusion proteins, bispecific molecules, and antibody fragments require researchers to constantly find innovative solutions. To increase yields and decrease costs of next generation bioprocesses, highly concentrated cell culture media formulations are developed but often limited by the low solubility of amino acids such as tyrosine, cystine, leucine, and isoleucine, in particular at physiological pH. This study sought to investigate highly soluble and bioavailable derivatives of leucine and isoleucine that are applicable for fed-batch processes. N-lactoyl-leucine and N-lactoyl-isoleucine sodium salts were tested in cell culture media and proved to be beneficial to increase the overall solubility of cell culture media formulations. These modified amino acids proved to be bioavailable for various Chinese hamster ovary (CHO) cells and were suitable for replacement of canonical amino acids in cell culture feeds. The quality of the final recombinant protein was studied in bioprocesses using the derivatives, and the mechanism of cleavage was investigated in CHO cells.
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  • The role of epigenetic regulation in immunity is emerging, especially for RNA N6-methyladenosine (m6A) modification. However, little is known about the role of m6A in the regulation of the immune microenvironment of periodontitis. Thus, we aim to investigate the impact of m6A modification in periodontitis immune microenvironment. The RNA modification patterns mediated by 23 m6A-regulators were systematically evaluated in 310 periodontitis samples. The impact of m6A modification on immune microenvironment characteristics was explored, including infiltrating immunocytes, immune reaction gene-sets and HLAs (human leukocyte antigen) gene. m6A phenotype-related immune genes were also identified. 17 m6A regulators were dysregulated and a 15-m6A regulator signature can well distinguish periodontitis and control samples. ALKBH5 and FMR1 are closely related to infiltrating monocyte abundance. ELAVL1 and CBLL1 are significant regulators in immune reaction of TNF_Family_Members_Receptors and Cytokine. The expression of HLA-B and HLA-DOA is affected by ALKBH5 and LRPPRC. 3 distinct RNA modification patterns mediated by 23 m6A regulators were identified. They differ from immunocyte abundance, immune reaction and HLA gene. 1631 m6A phenotype-related genes and 70 m6A-mediated immune genes were identified, and the biological functions of these were explored. Our finding demonstrated the m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment of periodontitis.
    The risk factors of early implant failure were controversial among previous studies, especially for implants in different sites.

    To analyze the rate and risk factors of early implant failure occurring before the placement of final prosthesis.

    A retrospective study was conducted based on electrical medical records of patients who received dental implant placement from 2015 to 2019. Generalized estimation equation analyses were used to explore potential risk factors influencing early implant failure.

    Overall, 6113 implants in 3785 patients were included. The rate of early implant failure was 1.6% at patient level and 1.2% at implant level. The early implant failure was significantly associated with implants in the posterior maxilla, with specific surface modifications and in previously augmented sites (p < 0.05). Risk factors for maxillary implants included surface modification and bone augmentation procedures (p < 0.01), whereas risk factors for mandibular implants included gender and bone augmentation procedures (p < 0.05). For implants placed in previously augmented sites, implants placed in the anterior mandible had a higher risk of early failure (p < 0.05).

    The risk factors for early implant failures varied among different sites; hence, they should be comprehensively considered in presurgical treatment plan.
    The risk factors for early implant failures varied among different sites; hence, they should be comprehensively considered in presurgical treatment plan.
    Sickle cell disease (SCD) is characterized by hemolysis-associated platelet dysfunction which leads to increased risk of thrombosis and plays a role in the high morbidity and mortality of the disease. The mechanisms by which hemolysis induces platelet activation remain unclear. We recently demonstrated that patients with SCD showed increased platelet mitochondrial reactive oxygen species (mtROS) production that correlates with markers of hemolysis and platelet activation. Experiments in isolated platelets demonstrated that mtROS stimulated platelet activation. However, the role of hemolysis-induced mtROS in thrombus formation in vivo remains unclear.

    Here, we hypothesize that scavenging of mtROS attenuates the propensity for thrombosis in mouse models of hemolysis.

    We show that infusion of hemolysate in wildtype **** induces platelet mtROS production and decreases time to vessel occlusion in a model of ferric chloride-induced carotid artery thrombosis. https://www.selleckchem.com/products/mi-3-menin-mll-inhibitor.html Increased mtROS and propensity for thrombosis was also observed in the Berkley transgenic mouse model of SCD, a chronic model of hemolysis. Notably, treatment with mtROS scavengers decreased platelet mtROS levels and attenuated the propensity for thrombus formation in both models.

    These data demonstrate that mtROS significantly contribute to the mechanism of hemolysis-induced thrombosis in vivo and suggest a potential role for mitochondrially-targeted antioxidant therapy in hemolysis and SCD-related thrombosis.
    These data demonstrate that mtROS significantly contribute to the mechanism of hemolysis-induced thrombosis in vivo and suggest a potential role for mitochondrially-targeted antioxidant therapy in hemolysis and SCD-related thrombosis.New spectroscopic methods were developed for dexlansoprazole estimation in capsule formulation based on the formation of a reaction between dexlansoprazole and Mercurochrome (MER) at pH 3.7. The formed complex was measured spectrophotometrically (Method I) at 557 nm and spectrofluorometrically (Method II) at 300 nm/538 nm, because the drug caused quantitative quenching of the native fluorescence of Mercurochrome. The spectrophotometric method was linear over the concentration 25-55 μg/ml with a limit of detection (LOD) of 1.15 μg/ml and a limit of quantification (LOQ) of 3.48 μg/ml. The spectrofluorometric method had a linear range 20-45 μg/ml with an LOD of 1.13 μg/ml and an LOQ of 3.45 μg/ml. The suggested methods were used to analyze capsules to test the interference from excipients and the data indicated good selectivity. Data obtained were statistically analyzed and were favourably good. The new methods are environmentally benign and depend on distilled water mainly as the diluting solvent. This property was confirmed by assessing their greenness.
    To evaluate the rate of surgical site infection (SSI) and associated risk factors after parotid gland surgery including the impact of antibiotic prophylaxis.

    Retrospective single-centre clinical study.

    Tertiary referral centre for head and neck surgery.

    Seven hundred and fifty four patients who underwent parotid gland surgery at the University Hospital Heidelberg, Germany, between 2007 and 2014 were enrolled in this study. Data on patient age, American Society of Anesthesiologists (ASA) classification system, smoking status, diabetes mellitus, operation time, and antibiotic prophylaxis were collected. Additionally, the National Healthcare Safety Network (NHSN) risk index was calculated. Association of these factors with SSI was evaluated in univariate analyses and a multivariate logistic regression model.

    Rate of SSI.

    Twenty four patients (3.2%) had an SSI according to the NHSN definition. In univariate analyses, only smokers (P=.048) and male patients (P=.01) had a significantly higher rate of SSI.
    The role of epigenetic regulation in immunity is emerging, especially for RNA N6-methyladenosine (m6A) modification. However, little is known about the role of m6A in the regulation of the immune microenvironment of periodontitis. Thus, we aim to investigate the impact of m6A modification in periodontitis immune microenvironment. The RNA modification patterns mediated by 23 m6A-regulators were systematically evaluated in 310 periodontitis samples. The impact of m6A modification on immune microenvironment characteristics was explored, including infiltrating immunocytes, immune reaction gene-sets and HLAs (human leukocyte antigen) gene. m6A phenotype-related immune genes were also identified. 17 m6A regulators were dysregulated and a 15-m6A regulator signature can well distinguish periodontitis and control samples. ALKBH5 and FMR1 are closely related to infiltrating monocyte abundance. ELAVL1 and CBLL1 are significant regulators in immune reaction of TNF_Family_Members_Receptors and Cytokine. The expression of HLA-B and HLA-DOA is affected by ALKBH5 and LRPPRC. 3 distinct RNA modification patterns mediated by 23 m6A regulators were identified. They differ from immunocyte abundance, immune reaction and HLA gene. 1631 m6A phenotype-related genes and 70 m6A-mediated immune genes were identified, and the biological functions of these were explored. Our finding demonstrated the m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment of periodontitis. The risk factors of early implant failure were controversial among previous studies, especially for implants in different sites. To analyze the rate and risk factors of early implant failure occurring before the placement of final prosthesis. A retrospective study was conducted based on electrical medical records of patients who received dental implant placement from 2015 to 2019. Generalized estimation equation analyses were used to explore potential risk factors influencing early implant failure. Overall, 6113 implants in 3785 patients were included. The rate of early implant failure was 1.6% at patient level and 1.2% at implant level. The early implant failure was significantly associated with implants in the posterior maxilla, with specific surface modifications and in previously augmented sites (p < 0.05). Risk factors for maxillary implants included surface modification and bone augmentation procedures (p < 0.01), whereas risk factors for mandibular implants included gender and bone augmentation procedures (p < 0.05). For implants placed in previously augmented sites, implants placed in the anterior mandible had a higher risk of early failure (p < 0.05). The risk factors for early implant failures varied among different sites; hence, they should be comprehensively considered in presurgical treatment plan. The risk factors for early implant failures varied among different sites; hence, they should be comprehensively considered in presurgical treatment plan. Sickle cell disease (SCD) is characterized by hemolysis-associated platelet dysfunction which leads to increased risk of thrombosis and plays a role in the high morbidity and mortality of the disease. The mechanisms by which hemolysis induces platelet activation remain unclear. We recently demonstrated that patients with SCD showed increased platelet mitochondrial reactive oxygen species (mtROS) production that correlates with markers of hemolysis and platelet activation. Experiments in isolated platelets demonstrated that mtROS stimulated platelet activation. However, the role of hemolysis-induced mtROS in thrombus formation in vivo remains unclear. Here, we hypothesize that scavenging of mtROS attenuates the propensity for thrombosis in mouse models of hemolysis. We show that infusion of hemolysate in wildtype mice induces platelet mtROS production and decreases time to vessel occlusion in a model of ferric chloride-induced carotid artery thrombosis. https://www.selleckchem.com/products/mi-3-menin-mll-inhibitor.html Increased mtROS and propensity for thrombosis was also observed in the Berkley transgenic mouse model of SCD, a chronic model of hemolysis. Notably, treatment with mtROS scavengers decreased platelet mtROS levels and attenuated the propensity for thrombus formation in both models. These data demonstrate that mtROS significantly contribute to the mechanism of hemolysis-induced thrombosis in vivo and suggest a potential role for mitochondrially-targeted antioxidant therapy in hemolysis and SCD-related thrombosis. These data demonstrate that mtROS significantly contribute to the mechanism of hemolysis-induced thrombosis in vivo and suggest a potential role for mitochondrially-targeted antioxidant therapy in hemolysis and SCD-related thrombosis.New spectroscopic methods were developed for dexlansoprazole estimation in capsule formulation based on the formation of a reaction between dexlansoprazole and Mercurochrome (MER) at pH 3.7. The formed complex was measured spectrophotometrically (Method I) at 557 nm and spectrofluorometrically (Method II) at 300 nm/538 nm, because the drug caused quantitative quenching of the native fluorescence of Mercurochrome. The spectrophotometric method was linear over the concentration 25-55 μg/ml with a limit of detection (LOD) of 1.15 μg/ml and a limit of quantification (LOQ) of 3.48 μg/ml. The spectrofluorometric method had a linear range 20-45 μg/ml with an LOD of 1.13 μg/ml and an LOQ of 3.45 μg/ml. The suggested methods were used to analyze capsules to test the interference from excipients and the data indicated good selectivity. Data obtained were statistically analyzed and were favourably good. The new methods are environmentally benign and depend on distilled water mainly as the diluting solvent. This property was confirmed by assessing their greenness. To evaluate the rate of surgical site infection (SSI) and associated risk factors after parotid gland surgery including the impact of antibiotic prophylaxis. Retrospective single-centre clinical study. Tertiary referral centre for head and neck surgery. Seven hundred and fifty four patients who underwent parotid gland surgery at the University Hospital Heidelberg, Germany, between 2007 and 2014 were enrolled in this study. Data on patient age, American Society of Anesthesiologists (ASA) classification system, smoking status, diabetes mellitus, operation time, and antibiotic prophylaxis were collected. Additionally, the National Healthcare Safety Network (NHSN) risk index was calculated. Association of these factors with SSI was evaluated in univariate analyses and a multivariate logistic regression model. Rate of SSI. Twenty four patients (3.2%) had an SSI according to the NHSN definition. In univariate analyses, only smokers (P=.048) and male patients (P=.01) had a significantly higher rate of SSI.
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  • There is no standard treatment for marginally resectable soft tissue sarcomas (STSs) of the extremities and trunk wall, and current approaches produce unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5 × 5 Gy hypofractionated radiotherapy can generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity.

    We conducted a single-arm prospective clinical trial. Treatment combined 1 cycle of AI with subsequent 5 × 5 Gy radiotherapy within 1 week, followed by 2 cycles of AI and surgery. The primary endpoint was to assess the number of patients in whom en bloc R0 resection was achieved.

    Forty-six patients met the eligibility criteria. Three patients had resectable lung metastases at baseline. Forty-two received the planned protocol treatment. In 2 patients, the treatment was prematurely stopped because of the toxicity of chemotherapy. One patient died of septic shock because of severe bone marrow suppression after the second AI cycle; a second death was not related to treatment for STS. Three patients underwent amputation. In 72% of patients in the intention-to-treat analysis, we achieved en bloc R0 resections. Grade 3+ Common Terminology Criteria for Adverse Events 4.03 chemotherapy toxicity requiring dose reduction or treatment interruption occurred in 15 patients. Wound complications occurred in 18 patients, but they were severe in only 6 patients.

    Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. Further evaluation of this strategy is warranted.
    Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. https://www.selleckchem.com/products/nedometinib.html Further evaluation of this strategy is warranted.Chronic cerebral ischemia leads to vascular cognitive impairment (VCI) that exacerbates along with ischemia time and eventually develops into dementia. Recent advances in molecular neuroimaging contribute to understand its pathological characteristics. We previously traced the anisotropic diffusion of water molecules suggests that chronic cerebral ischemia leads to irreversible progressive damage to white matter integrity. However, the abnormalities of gray matter activity following chronic cerebral ischemia remains not entirely understood. In this study, in vivo hydrogen proton magnetic resonance spectroscopy (1H-MRS) was applied to longitudinally track the neurochemical metabolic disorder of gray matter associated with working memory, and optogenetics modulation of neurochemical metabolism was performed for targeted treatment of VCI. The results showed that the concentration of N-acetylaspartate (NAA) in the right hippocampus, left hippocampus, right medial prefrontal cortex (mPFC) and mediodorsal thalamus modulation of parvalbumin (PV) neurons in the mPFC can improve the neurochemical metabolism of working memory neural circuit and enhance working memory.Previous studies have shown that alterations in autophagy-related proteins exist extensively after traumatic brain injury (TBI). However, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, a controlled cortical impact was used to establish a model of moderate TBI in rats. We found that a significant increase in protein levels of LC3-II and SQSTM1 in the injured cortex group. However, there were no significant differences in protein levels of VPS34, Beclin-1, and phosphor-ULK1, which are the promoters of autophagy. Lysosome dysfunction after TBI might lead to autophagosome accumulation. In addition, the highly specific autophagy inhibitor SAR405 administration reduced TBI-induced apoptosis-related protein cleaved caspase-3 and cleaved caspase-9 levels in the ipsilateral cortex, as well as brain edema and neurological defects accessed by mNSS. Furthermore, chloroquine treatment reversed the beneficial effects of SAR405 by increasing the accumulation of autophagosomes. Finally, our data showed that autophagy inhibition by VPS34 gene knockout method attenuated cell death after TBI. Our findings indicate that impaired autophagosome degradation is involved in the pathological reaction after TBI, and the inhibition of autophagy contributes to attenuate neuronal cell death and functional defects.Brain EGR1 (early growth response protein 1) overexpression aggravates focal ischemic brain injury, but its role in intracerebral hemorrhage (ICH) induced cerebral injury remains obscure. In this study, a rat ICH model was established by injecting type VII collagenase into the brain, and EGR1 knockdown reversed the increase of hematoma area, neurological function score, brain water content, blood-brain barrier (BBB) permeability, inflammation, p300 and retinoid a X receptor-α (RXRα) protein levels, as well as RXRα acetylation level induced by ICH. EGR1 expression was up-regulated in primary brain microvascular endothelial cells (BMECs), neurons, and astrocytes after ICH induction, and the up-regulation was most significant in BMECs. We also found that EGR1 promoted RXRα acetylation level by regulating p300 in BMECs. Silencing EGR1 rescued the upregulation of cell inflammation and the reduction of cell viability and TEER (transendothelial electric resistance) caused by OGD (oxygen glucose deprivation) plus hemin via p300-mediated RXRα acetylation. Furthermore, the STAT3/NF-κB pathway was activated after treatment with OGD plus hemin, which was suppressed by silencing EGR1. Treatment with Stattic (an inhibitor of STAT3) restrained the effect of OGD plus hemin on NF-κB pathway activity, inflammation, cell viability and TEER. In conclusion, EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, Through the STAT3/NF-κB pathway.The novel coronavirus 2019 (COVID-19) pandemic has placed an unprecedented strain on healthcare systems and frontline workers worldwide. The large influx of these high acuity patients has placed pressure on services to modify their operations to meet this increased need. We describe how the Vascular Access Service (VAS) at a New York City academic hospital adopted a team-based approach to efficiently meet increased demand for vascular access devices, while ensuring safety and conserving personal protective equipment.
    There is no standard treatment for marginally resectable soft tissue sarcomas (STSs) of the extremities and trunk wall, and current approaches produce unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5 × 5 Gy hypofractionated radiotherapy can generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity. We conducted a single-arm prospective clinical trial. Treatment combined 1 cycle of AI with subsequent 5 × 5 Gy radiotherapy within 1 week, followed by 2 cycles of AI and surgery. The primary endpoint was to assess the number of patients in whom en bloc R0 resection was achieved. Forty-six patients met the eligibility criteria. Three patients had resectable lung metastases at baseline. Forty-two received the planned protocol treatment. In 2 patients, the treatment was prematurely stopped because of the toxicity of chemotherapy. One patient died of septic shock because of severe bone marrow suppression after the second AI cycle; a second death was not related to treatment for STS. Three patients underwent amputation. In 72% of patients in the intention-to-treat analysis, we achieved en bloc R0 resections. Grade 3+ Common Terminology Criteria for Adverse Events 4.03 chemotherapy toxicity requiring dose reduction or treatment interruption occurred in 15 patients. Wound complications occurred in 18 patients, but they were severe in only 6 patients. Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. Further evaluation of this strategy is warranted. Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. https://www.selleckchem.com/products/nedometinib.html Further evaluation of this strategy is warranted.Chronic cerebral ischemia leads to vascular cognitive impairment (VCI) that exacerbates along with ischemia time and eventually develops into dementia. Recent advances in molecular neuroimaging contribute to understand its pathological characteristics. We previously traced the anisotropic diffusion of water molecules suggests that chronic cerebral ischemia leads to irreversible progressive damage to white matter integrity. However, the abnormalities of gray matter activity following chronic cerebral ischemia remains not entirely understood. In this study, in vivo hydrogen proton magnetic resonance spectroscopy (1H-MRS) was applied to longitudinally track the neurochemical metabolic disorder of gray matter associated with working memory, and optogenetics modulation of neurochemical metabolism was performed for targeted treatment of VCI. The results showed that the concentration of N-acetylaspartate (NAA) in the right hippocampus, left hippocampus, right medial prefrontal cortex (mPFC) and mediodorsal thalamus modulation of parvalbumin (PV) neurons in the mPFC can improve the neurochemical metabolism of working memory neural circuit and enhance working memory.Previous studies have shown that alterations in autophagy-related proteins exist extensively after traumatic brain injury (TBI). However, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, a controlled cortical impact was used to establish a model of moderate TBI in rats. We found that a significant increase in protein levels of LC3-II and SQSTM1 in the injured cortex group. However, there were no significant differences in protein levels of VPS34, Beclin-1, and phosphor-ULK1, which are the promoters of autophagy. Lysosome dysfunction after TBI might lead to autophagosome accumulation. In addition, the highly specific autophagy inhibitor SAR405 administration reduced TBI-induced apoptosis-related protein cleaved caspase-3 and cleaved caspase-9 levels in the ipsilateral cortex, as well as brain edema and neurological defects accessed by mNSS. Furthermore, chloroquine treatment reversed the beneficial effects of SAR405 by increasing the accumulation of autophagosomes. Finally, our data showed that autophagy inhibition by VPS34 gene knockout method attenuated cell death after TBI. Our findings indicate that impaired autophagosome degradation is involved in the pathological reaction after TBI, and the inhibition of autophagy contributes to attenuate neuronal cell death and functional defects.Brain EGR1 (early growth response protein 1) overexpression aggravates focal ischemic brain injury, but its role in intracerebral hemorrhage (ICH) induced cerebral injury remains obscure. In this study, a rat ICH model was established by injecting type VII collagenase into the brain, and EGR1 knockdown reversed the increase of hematoma area, neurological function score, brain water content, blood-brain barrier (BBB) permeability, inflammation, p300 and retinoid a X receptor-α (RXRα) protein levels, as well as RXRα acetylation level induced by ICH. EGR1 expression was up-regulated in primary brain microvascular endothelial cells (BMECs), neurons, and astrocytes after ICH induction, and the up-regulation was most significant in BMECs. We also found that EGR1 promoted RXRα acetylation level by regulating p300 in BMECs. Silencing EGR1 rescued the upregulation of cell inflammation and the reduction of cell viability and TEER (transendothelial electric resistance) caused by OGD (oxygen glucose deprivation) plus hemin via p300-mediated RXRα acetylation. Furthermore, the STAT3/NF-κB pathway was activated after treatment with OGD plus hemin, which was suppressed by silencing EGR1. Treatment with Stattic (an inhibitor of STAT3) restrained the effect of OGD plus hemin on NF-κB pathway activity, inflammation, cell viability and TEER. In conclusion, EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, Through the STAT3/NF-κB pathway.The novel coronavirus 2019 (COVID-19) pandemic has placed an unprecedented strain on healthcare systems and frontline workers worldwide. The large influx of these high acuity patients has placed pressure on services to modify their operations to meet this increased need. We describe how the Vascular Access Service (VAS) at a New York City academic hospital adopted a team-based approach to efficiently meet increased demand for vascular access devices, while ensuring safety and conserving personal protective equipment.
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  • Development of novel technologies provides the best tissue constructs engineering and maximizes their therapeutic effects in regenerative therapy, especially for liver dysfunctions. Among the currently investigated approaches of tissue engineering, scaffold-based and scaffold-free tissues are widely suggested for liver regeneration. Analogs of liver acellular extracellular matrix (ECM) are utilized in native scaffolds to increase the self-repair and healing ability of organs. Native ECM analog could improve liver repairing through providing the supportive framework for cells and signaling molecules, exerting normal biomechanical, biochemical, and physiological signal complexes. Recently, innovative cell sheet technology is introduced as an alternative for conventional tissue engineering with the advantage of fewer scaffold restrictions and cell culture on a Thermo-Responsive Polymer Surface. These sheets release the layered cells through a temperature-controlled procedure without enzymatic digestion, while preserving the cell-ECM contacts and adhesive molecules on cell-cell junctions. In addition, several novelties have been introduced into the cell sheet and decellularization technologies to aid cell growth, instruct differentiation/angiogenesis, and promote cell migration. In this review, recent trends, advancements, and issues linked to translation into clinical practice are dissected and compared regarding the decellularization and cell sheet technologies for liver tissue engineering.MiR-375, a primitively described beta cell-specific miRNA, is confirmed to function as multi-functional regulator in diverse typical cellular pathways according to the follow-up researches. Based on the existing studies, miR-375 can regulate many functional genes and ectopic expressions of miR-375 are usually associated with pathological changes, and its expression regulation mechanism is mainly related to promoter methylation or circRNA. In this review, the regulatory functions of miR-375 in immunity, such as its relevance with macrophages, T helper cells and autoimmune diseases were briefly discussed. Also, the functions of miR-375 involved in inflammation, development and virus replication were reviewed. Finally, the mechanisms and application prospects of miR-375 in cancers were analyzed. Studies show that the application of miR-375 as therapeutic target and biomarker has a broad developing space in future. We hope this paper can provide reference for its further study.
    This study aimed to investigate the gastroprotective effect of chlorogenic acid (CGA) against Indomethacin (IND)-induced gastric ulcer (**) in rats and its underlying mechanism, especially through autophagic and apoptotic pathways.

    Seventy-five rats were divided into five groups; control, IND (50mg/kg, p.o.), CGA (100mg/kg, p.o., 14days), IND pretreated with CGA (50mg/kg or 100mg/kg, p.o., 14days). The stomach tissues were examined to calculate the ulcer index and analyze markers of autophagy (beclin-1, LC3-II/LC3-I and p62), lysosomal function (cathepsin-D) and apoptosis (Bcl-2, Bax and caspase-3), along with expression of Akt/mTOR pathway using western blot or ELISA techniques. In addition, viability of gastric mucosal cells was detected by flowcytometry. Structural changes were assessed histologically, while autophagic and apoptotic changes of gastric mucosa were observed by transmission electron microscopy.

    CGA exhibited a dose-dependent gastroprotective effect by reversing IND-induced accumulation /mTOR pathway reactivation, and alleviation of IND-induced lysosomal dysfunction.Human neurodegenerative polyglutamine [poly(Q)] disorders, such as Huntington's disease (HD) and spinocerebellar ataxias (SCA), are characterised by an abnormal expansion of CAG repeats in the affected gene. https://www.selleckchem.com/products/heparin.html The mutated proteins misfold and aggregate to form inclusion bodies that sequester important factors involved in cellular transcription, growth, stress and autophagic response and other essential functions. The insulin signalling pathway has been demonstrated as a major modifier and a potential drug target to ameliorate the poly(Q) mediated neurotoxicity in various model systems. Insulin signalling cascade harbours several downstream sub-pathways, which are synergistically involved in discharging indispensable biological functions such as growth and proliferation, metabolism, autophagy, regulation of cell death pathways etc. Hence, it is difficult to conclude whether the mitigation of poly(Q) neurotoxicity is an accumulative outcome of the insulin cascade, or the result of a specific sub-pathway. For the first time, we report that the ligand binding domain of insulin receptor mediated downstream growth promoting sub-pathway plays the pivotal role in operating the rescue event. We show that the growth promoting activity of insulin cascade is essential to minimize the abundance of inclusion bodies, to restrict neurodegeneration, and to restore the cellular transcriptional balance. Subsequently, we noted the involvement of the mTOR/S6k/4E-BP candidates in mitigating poly(Q) mediated neurotoxicity. Due to the conserved cellular functioning of the insulin cascade across species, and availability of several growth promoting molecules, our results in Drosophila poly(Q) models indicate towards a possibility of designing novel therapeutic strategies to restrict the pathogenesis of devastating human poly(Q) disorders.Gender differences in emotion regulation (ER) have been postulated, yet their neural basis remains poorly understood. The goal of this study was to investigate this issue from a functional connectivity (FC) perspective. Utilizing a region of interest (ROI) analysis, we investigated whether men and women (N = 48) differed in their FC pattern while viewing versus regulating negative emotion induced by highly salient pictures, and whether this pattern related to their self-reported negative affect and suppression success. Despite women reporting more negative affect, both genders had comparable suppression success. Moreover, differences emerged between men and women's FC patterns. During the regulation of negative emotion, better suppression in women was associated with stronger FC within a cingulo-opercular network, while men exhibited stronger FC within posterior regions of the ventral attentional network. We conclude that due to their propensity for higher emotional reactivity, women may employ a frontal top-down control network to downregulate negative emotion, while men may redirect attention away from the negative stimulus by using posterior regions of the ventral attention network.
    Development of novel technologies provides the best tissue constructs engineering and maximizes their therapeutic effects in regenerative therapy, especially for liver dysfunctions. Among the currently investigated approaches of tissue engineering, scaffold-based and scaffold-free tissues are widely suggested for liver regeneration. Analogs of liver acellular extracellular matrix (ECM) are utilized in native scaffolds to increase the self-repair and healing ability of organs. Native ECM analog could improve liver repairing through providing the supportive framework for cells and signaling molecules, exerting normal biomechanical, biochemical, and physiological signal complexes. Recently, innovative cell sheet technology is introduced as an alternative for conventional tissue engineering with the advantage of fewer scaffold restrictions and cell culture on a Thermo-Responsive Polymer Surface. These sheets release the layered cells through a temperature-controlled procedure without enzymatic digestion, while preserving the cell-ECM contacts and adhesive molecules on cell-cell junctions. In addition, several novelties have been introduced into the cell sheet and decellularization technologies to aid cell growth, instruct differentiation/angiogenesis, and promote cell migration. In this review, recent trends, advancements, and issues linked to translation into clinical practice are dissected and compared regarding the decellularization and cell sheet technologies for liver tissue engineering.MiR-375, a primitively described beta cell-specific miRNA, is confirmed to function as multi-functional regulator in diverse typical cellular pathways according to the follow-up researches. Based on the existing studies, miR-375 can regulate many functional genes and ectopic expressions of miR-375 are usually associated with pathological changes, and its expression regulation mechanism is mainly related to promoter methylation or circRNA. In this review, the regulatory functions of miR-375 in immunity, such as its relevance with macrophages, T helper cells and autoimmune diseases were briefly discussed. Also, the functions of miR-375 involved in inflammation, development and virus replication were reviewed. Finally, the mechanisms and application prospects of miR-375 in cancers were analyzed. Studies show that the application of miR-375 as therapeutic target and biomarker has a broad developing space in future. We hope this paper can provide reference for its further study. This study aimed to investigate the gastroprotective effect of chlorogenic acid (CGA) against Indomethacin (IND)-induced gastric ulcer (GU) in rats and its underlying mechanism, especially through autophagic and apoptotic pathways. Seventy-five rats were divided into five groups; control, IND (50mg/kg, p.o.), CGA (100mg/kg, p.o., 14days), IND pretreated with CGA (50mg/kg or 100mg/kg, p.o., 14days). The stomach tissues were examined to calculate the ulcer index and analyze markers of autophagy (beclin-1, LC3-II/LC3-I and p62), lysosomal function (cathepsin-D) and apoptosis (Bcl-2, Bax and caspase-3), along with expression of Akt/mTOR pathway using western blot or ELISA techniques. In addition, viability of gastric mucosal cells was detected by flowcytometry. Structural changes were assessed histologically, while autophagic and apoptotic changes of gastric mucosa were observed by transmission electron microscopy. CGA exhibited a dose-dependent gastroprotective effect by reversing IND-induced accumulation /mTOR pathway reactivation, and alleviation of IND-induced lysosomal dysfunction.Human neurodegenerative polyglutamine [poly(Q)] disorders, such as Huntington's disease (HD) and spinocerebellar ataxias (SCA), are characterised by an abnormal expansion of CAG repeats in the affected gene. https://www.selleckchem.com/products/heparin.html The mutated proteins misfold and aggregate to form inclusion bodies that sequester important factors involved in cellular transcription, growth, stress and autophagic response and other essential functions. The insulin signalling pathway has been demonstrated as a major modifier and a potential drug target to ameliorate the poly(Q) mediated neurotoxicity in various model systems. Insulin signalling cascade harbours several downstream sub-pathways, which are synergistically involved in discharging indispensable biological functions such as growth and proliferation, metabolism, autophagy, regulation of cell death pathways etc. Hence, it is difficult to conclude whether the mitigation of poly(Q) neurotoxicity is an accumulative outcome of the insulin cascade, or the result of a specific sub-pathway. For the first time, we report that the ligand binding domain of insulin receptor mediated downstream growth promoting sub-pathway plays the pivotal role in operating the rescue event. We show that the growth promoting activity of insulin cascade is essential to minimize the abundance of inclusion bodies, to restrict neurodegeneration, and to restore the cellular transcriptional balance. Subsequently, we noted the involvement of the mTOR/S6k/4E-BP candidates in mitigating poly(Q) mediated neurotoxicity. Due to the conserved cellular functioning of the insulin cascade across species, and availability of several growth promoting molecules, our results in Drosophila poly(Q) models indicate towards a possibility of designing novel therapeutic strategies to restrict the pathogenesis of devastating human poly(Q) disorders.Gender differences in emotion regulation (ER) have been postulated, yet their neural basis remains poorly understood. The goal of this study was to investigate this issue from a functional connectivity (FC) perspective. Utilizing a region of interest (ROI) analysis, we investigated whether men and women (N = 48) differed in their FC pattern while viewing versus regulating negative emotion induced by highly salient pictures, and whether this pattern related to their self-reported negative affect and suppression success. Despite women reporting more negative affect, both genders had comparable suppression success. Moreover, differences emerged between men and women's FC patterns. During the regulation of negative emotion, better suppression in women was associated with stronger FC within a cingulo-opercular network, while men exhibited stronger FC within posterior regions of the ventral attentional network. We conclude that due to their propensity for higher emotional reactivity, women may employ a frontal top-down control network to downregulate negative emotion, while men may redirect attention away from the negative stimulus by using posterior regions of the ventral attention network.
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  • measures to combat this pandemic should not affect routine immunization programmes, especially in our resource-constrained country. https://www.selleckchem.com/products/LY2228820.html It is essential to continue vaccination schedule for children and to identify children who have missed vaccine doses in order to implement catch-up vaccination.
    measures to combat this pandemic should not affect routine immunization programmes, especially in our resource-constrained country. It is essential to continue vaccination schedule for children and to identify children who have missed vaccine doses in order to implement catch-up vaccination.COVID-19 is caused by SARS-CoV-2 virus, which is genetically similar to severe acute respiratory syndrome (SARS) virus. In pediatrics, it has a benign clinical course. Since the outbreak of COVID-19 pandemic in Guinea, whose epicenter was Conakry, pediatric cases have been reported at the CTEIP in Donka. The purpose of this study was to determine their epidemiological profile. We conducted a descriptive cross-sectional study of children aged 0-16 years admitted to the CTEIP, Donka, over a period of four months. Out of 7308 patients, coming predominantly from 5 communes of Conakry and hospitalized in the CTEPI, 189 were aged between 0 and 16 years (2 .59%). The majority of patients were within the age-group 0-4-years (38.62%) with a sex-ratio (F/M) of 1.52; 62.96% were students, 70% of children lived in Conakry, 28.57% of mothers were traders and contact persons (39.68%); 37.57% of fathers were civil servants, 2.65% of children had a history of sickle cell disease and 1.59% had allergic rhinitis. Asymptomatic patients accounted for 52.38% of cases and diagnosed patients were 74.6%. Symptoms included fever, rhinorrhea, headache, cough, abdominal pain, sneezing, diarrhea, physical asthenia. The incidence of COVID-19 among children hospitalized in the CTEIP of Donka is low. Children aged 5 years and older are more affected and nearly 50% are asymptomatic. Common symptoms are fever, headache, rhinorrhea, cough, abdominal pain, sneezing, diarrhea, physical asthenia.
    mobile health technologies are increasingly being used as innovative solutions to improve antenatal care in Primary Care Services (PCSs). This study assessed the acceptability and satisfaction with PANDA system used in PCSs in Burkina Faso.

    we conducted a cross-sectional mixed-methods study of 35 users of PCSs and 35 health workers in the Koupela Health District, in the Central East region of Burkina Faso in September 2017. Interviews and 4 focus groups were conducted among PCSs users and semi-structured interviews among health-care professionals. Quantitative data analysis was carried out using the SPSS software and qualitative data analysis using a thematic analysis with NVivo 10.

    PANDA system was very well accepted and appreciated by users and healthcare providers. Factors influencing customer satisfaction included the improvement of interactions with health care providers and the access to better quality care at lower cost. Health care providers appreciated the relevance of PANDA system as well as service improvements, follow-up and monitoring of pregnant women.

    in primary health-care system in Burkina Faso, PANDA system is very well accepted and appreciated by both health care providers and users of prenatal care services.
    in primary health-care system in Burkina Faso, PANDA system is very well accepted and appreciated by both health care providers and users of prenatal care services.Idiopathic velopharyngeal insufficiency is a rare clinical entity. Typical clinical features are rhinolalia and nasopharyngeal regurgitation. It is usually observed in children. We report a case of a 28-year-old female with this rare disorder. The symptoms were rhinolalia and regurgitation of liquids into the nose. The magnetic resonance imaging of the brain and upper cervical region was normal. The infectious serologies were negative.
    the prevalence of denture related mucosa lesions (DRML) varies across different countries and a recent study reported an increasing trend in its prevalence. The objective of this study was to determine the prevalence of DRML and factors related to the lesions among denture wearers seen in a Nigerian teaching hospital.

    interviewer's administered questionnaire was used to obtain information from consecutive patients that had used removable denture for at least six months and consented to participate. Data related to gender, age, types of denture and presence of denture induced oral lesions were obtained, entered into a computer and analyzed using IBM SPSS Version 20. Descriptive statistics were expressed as frequency and percentages. Fisher's exact test was performed for discrete variables. A P-value less than 0.05 was regarded as statistically significant.

    a total of 104 respondents participated in the study and 14 had DRML giving a prevalence of 13.5%. The majority, 11 out of the 14 (78.57%) presented with mucosa ulceration, while 8 (57.14%) out of the 14 cases of DRML were caused by over extension of the denture flanges. There was no statistically significant relationship between daily removal of denture fore going to bed to sleep at night and DRML (p=0.776).

    the prevalence of denture related mucosal lesion was 13.3% and the major cause was over extension of denture flange. There is need to emphasize adherence to review appointments for early detection and correction of denture instability and over extension of denture flange to prevent DRML.
    the prevalence of denture related mucosal lesion was 13.3% and the major cause was over extension of denture flange. There is need to emphasize adherence to review appointments for early detection and correction of denture instability and over extension of denture flange to prevent DRML.
    in Rwanda, the estimated out-of-pocket health expenditure has been increased from 24.46% in 2000 to 26% in 2015. Despite the existence of guideline in estimation of out-of-pocket health expenditures provided by WHO (2018), the estimation of out-of-pocket health expenditure still have difficulties in many countries including Rwanda.

    the purpose of this paper was to figure out the best model which predicts the out-of-pocket health expenditures in Rwanda during the process of considering various techniques of machine learning by using the Rwanda Integrated Living Conditions Surveys (EICV5) of 14580 households (2018).

    our findings presented the model which predict the out-of-pocket health expenditures with higher accuracy and was found as treenet model. Furthermore, machine learning techniques were used to judge which predictor variable was important in our prediction process and comparison of the performance of the algorithms through train accuracy and test accuracy metric measures. Finally, the findings show that the tests of accuracy of the models were 50.
    measures to combat this pandemic should not affect routine immunization programmes, especially in our resource-constrained country. https://www.selleckchem.com/products/LY2228820.html It is essential to continue vaccination schedule for children and to identify children who have missed vaccine doses in order to implement catch-up vaccination. measures to combat this pandemic should not affect routine immunization programmes, especially in our resource-constrained country. It is essential to continue vaccination schedule for children and to identify children who have missed vaccine doses in order to implement catch-up vaccination.COVID-19 is caused by SARS-CoV-2 virus, which is genetically similar to severe acute respiratory syndrome (SARS) virus. In pediatrics, it has a benign clinical course. Since the outbreak of COVID-19 pandemic in Guinea, whose epicenter was Conakry, pediatric cases have been reported at the CTEIP in Donka. The purpose of this study was to determine their epidemiological profile. We conducted a descriptive cross-sectional study of children aged 0-16 years admitted to the CTEIP, Donka, over a period of four months. Out of 7308 patients, coming predominantly from 5 communes of Conakry and hospitalized in the CTEPI, 189 were aged between 0 and 16 years (2 .59%). The majority of patients were within the age-group 0-4-years (38.62%) with a sex-ratio (F/M) of 1.52; 62.96% were students, 70% of children lived in Conakry, 28.57% of mothers were traders and contact persons (39.68%); 37.57% of fathers were civil servants, 2.65% of children had a history of sickle cell disease and 1.59% had allergic rhinitis. Asymptomatic patients accounted for 52.38% of cases and diagnosed patients were 74.6%. Symptoms included fever, rhinorrhea, headache, cough, abdominal pain, sneezing, diarrhea, physical asthenia. The incidence of COVID-19 among children hospitalized in the CTEIP of Donka is low. Children aged 5 years and older are more affected and nearly 50% are asymptomatic. Common symptoms are fever, headache, rhinorrhea, cough, abdominal pain, sneezing, diarrhea, physical asthenia. mobile health technologies are increasingly being used as innovative solutions to improve antenatal care in Primary Care Services (PCSs). This study assessed the acceptability and satisfaction with PANDA system used in PCSs in Burkina Faso. we conducted a cross-sectional mixed-methods study of 35 users of PCSs and 35 health workers in the Koupela Health District, in the Central East region of Burkina Faso in September 2017. Interviews and 4 focus groups were conducted among PCSs users and semi-structured interviews among health-care professionals. Quantitative data analysis was carried out using the SPSS software and qualitative data analysis using a thematic analysis with NVivo 10. PANDA system was very well accepted and appreciated by users and healthcare providers. Factors influencing customer satisfaction included the improvement of interactions with health care providers and the access to better quality care at lower cost. Health care providers appreciated the relevance of PANDA system as well as service improvements, follow-up and monitoring of pregnant women. in primary health-care system in Burkina Faso, PANDA system is very well accepted and appreciated by both health care providers and users of prenatal care services. in primary health-care system in Burkina Faso, PANDA system is very well accepted and appreciated by both health care providers and users of prenatal care services.Idiopathic velopharyngeal insufficiency is a rare clinical entity. Typical clinical features are rhinolalia and nasopharyngeal regurgitation. It is usually observed in children. We report a case of a 28-year-old female with this rare disorder. The symptoms were rhinolalia and regurgitation of liquids into the nose. The magnetic resonance imaging of the brain and upper cervical region was normal. The infectious serologies were negative. the prevalence of denture related mucosa lesions (DRML) varies across different countries and a recent study reported an increasing trend in its prevalence. The objective of this study was to determine the prevalence of DRML and factors related to the lesions among denture wearers seen in a Nigerian teaching hospital. interviewer's administered questionnaire was used to obtain information from consecutive patients that had used removable denture for at least six months and consented to participate. Data related to gender, age, types of denture and presence of denture induced oral lesions were obtained, entered into a computer and analyzed using IBM SPSS Version 20. Descriptive statistics were expressed as frequency and percentages. Fisher's exact test was performed for discrete variables. A P-value less than 0.05 was regarded as statistically significant. a total of 104 respondents participated in the study and 14 had DRML giving a prevalence of 13.5%. The majority, 11 out of the 14 (78.57%) presented with mucosa ulceration, while 8 (57.14%) out of the 14 cases of DRML were caused by over extension of the denture flanges. There was no statistically significant relationship between daily removal of denture fore going to bed to sleep at night and DRML (p=0.776). the prevalence of denture related mucosal lesion was 13.3% and the major cause was over extension of denture flange. There is need to emphasize adherence to review appointments for early detection and correction of denture instability and over extension of denture flange to prevent DRML. the prevalence of denture related mucosal lesion was 13.3% and the major cause was over extension of denture flange. There is need to emphasize adherence to review appointments for early detection and correction of denture instability and over extension of denture flange to prevent DRML. in Rwanda, the estimated out-of-pocket health expenditure has been increased from 24.46% in 2000 to 26% in 2015. Despite the existence of guideline in estimation of out-of-pocket health expenditures provided by WHO (2018), the estimation of out-of-pocket health expenditure still have difficulties in many countries including Rwanda. the purpose of this paper was to figure out the best model which predicts the out-of-pocket health expenditures in Rwanda during the process of considering various techniques of machine learning by using the Rwanda Integrated Living Conditions Surveys (EICV5) of 14580 households (2018). our findings presented the model which predict the out-of-pocket health expenditures with higher accuracy and was found as treenet model. Furthermore, machine learning techniques were used to judge which predictor variable was important in our prediction process and comparison of the performance of the algorithms through train accuracy and test accuracy metric measures. Finally, the findings show that the tests of accuracy of the models were 50.
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  • In patients, the rate of severe vessel dissection was significantly lower in the SSI than non-SSI group (17.6% vs. 55.2%, respectively; P less then 0.001). Multivariate regression analysis revealed that SSI was an independent factor preventing severe dissection (odds ratio 0.18; 95% confidence interval 0.06-0.53; P=0.002). Conclusions SSI is a gentle and effective method for the preparation of femoropopliteal lesions to reduce the incidence of severe angiographic dissection when using drug-coated balloons.Background Sleep disordered breathing (SDB) is prevalent and associated with increased mortality in patients both with and without cardiovascular disease (CVD). Many portable monitoring devices, including peripheral arterial tonometry (PAT)-based devices, have been developed. Although previous studies have demonstrated that the apnea-hypopnea index (AHI) determined by PAT devices (pAHI) is strongly correlated with AHI determined by polysomnography (AHI-PSG), no data have been reported from a Japanese patient population or patients with CVD. In this study we compared the parameters determined by PAT-based devices with those determined by polysomnography in Japanese patients with CVD. Methods and Results We enrolled 120 patients undergoing overnight polysomnography at 6 Japanese centers. A PAT-based device was used simultaneously with polysomnography. Polysomnography recordings were scored centrally by a technician in a blinded manner. PAT-based device recordings were scored using an automatic algorithm. There was a strong correlation between pAHI and AHI-PSG (r=0.896; P less then 0.001) with acceptable agreement. The strong correlation between pAHI and AHI-PSG was observed in patients with CVD (n=55; P=0.849; P less then 0.001) and without CVD (n=65; r=0.927; P less then 0.001). The presence or absence of CVD did not affect the relationship between pAHI and AHI-PSG (P=0.225). Conclusions A PAT-based device provides a reliable AHI in a Japanese patient population, even in patients with CVD. These findings may help reduce the number of patients with undiagnosed SDB and CVD.Background We hypothesized that the intracoronary-electrocardiogram (IC-ECG)-based pressure index would be more stable and precise than the instantaneous flow reserve (iFR). We investigated the usefulness of the IC-ECG-based pressure index for diagnosing myocardial ischemia. Methods and Results Thirty-seven consecutive patients with coronary stenosis requiring physiological assessment were enrolled in the study. iFR was measured at rest and under hyperemia in 51 and 40 lesions, respectively. The IC-ECG-triggered distal pressure (Pd)/aortic pressure (Pa) ratio (ICE-T) was defined as the mean Pd/Pa ratio in the period corresponding to the isoelectric line. The ICE-T was significantly lower than the iFR both at rest and during hyperemia (P less then 0.00001 for both). https://www.selleckchem.com/products/inixaciclib.html Fluctuations in the ICE-T pressure parameters (Pd/Pa, Pa, and Pd) were significantly smaller than those of iFR both at rest and during hyperemia. The diagnostic accuracy of predicting a fractional flow reserve (FFR) ≤0.80 of the ICE-T at rest was significantly higher than that of iFR (P=0.008). Receiver operating characteristic curve analyses showed that the ICE-T predicts FFR ≤0.80 more accurately than the iFR (area under curve 0.897 vs. 0.810 for ICE-T and iFR, respectively). Conclusions We identified the period in the IC-ECG in which resting Pd/Pa was low and constant. The IC-ECG-based algorithm may improve the accuracy of diagnosing myocardial ischemia, without increasing invasiveness, compared with pressure-dependent indices.Background The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF.Background Complete left atrial posterior wall isolation (LAPI) is not always achieved. We examined whether incomplete LAPI has an effect on outcomes after catheter ablation (CA). Methods and Results This study enrolled 75 consecutive patients (mean [±SD] age 62.6±8.9 years, 74.7% male) who underwent LAPI by radiofrequency CA for persistent atrial fibrillation (AF). The median follow-up period was 541 days (interquartile range 338-840 days). Incomplete LAPI was defined as the presence of a successfully created roof or floor linear lesion. The rate of complete LAPI was 41.3% (31/75). Either a roof or floor linear lesion was created in 38 patients, whereas neither was created in 6. Multivariate Cox proportional hazards regression analysis revealed that female sex (hazard ratio [HR] 5.29; 95% confidence interval [CI] 1.81-16.8; P=0.002) and complete or incomplete LAPI (HR 0.17; 95% CI 0.03-0.79; P=0.027) were independent predictors of AF recurrence. Kaplan-Meier curves indicated that better outcome was associated with at least one rather than no successful linear lesion (86.
    In patients, the rate of severe vessel dissection was significantly lower in the SSI than non-SSI group (17.6% vs. 55.2%, respectively; P less then 0.001). Multivariate regression analysis revealed that SSI was an independent factor preventing severe dissection (odds ratio 0.18; 95% confidence interval 0.06-0.53; P=0.002). Conclusions SSI is a gentle and effective method for the preparation of femoropopliteal lesions to reduce the incidence of severe angiographic dissection when using drug-coated balloons.Background Sleep disordered breathing (SDB) is prevalent and associated with increased mortality in patients both with and without cardiovascular disease (CVD). Many portable monitoring devices, including peripheral arterial tonometry (PAT)-based devices, have been developed. Although previous studies have demonstrated that the apnea-hypopnea index (AHI) determined by PAT devices (pAHI) is strongly correlated with AHI determined by polysomnography (AHI-PSG), no data have been reported from a Japanese patient population or patients with CVD. In this study we compared the parameters determined by PAT-based devices with those determined by polysomnography in Japanese patients with CVD. Methods and Results We enrolled 120 patients undergoing overnight polysomnography at 6 Japanese centers. A PAT-based device was used simultaneously with polysomnography. Polysomnography recordings were scored centrally by a technician in a blinded manner. PAT-based device recordings were scored using an automatic algorithm. There was a strong correlation between pAHI and AHI-PSG (r=0.896; P less then 0.001) with acceptable agreement. The strong correlation between pAHI and AHI-PSG was observed in patients with CVD (n=55; P=0.849; P less then 0.001) and without CVD (n=65; r=0.927; P less then 0.001). The presence or absence of CVD did not affect the relationship between pAHI and AHI-PSG (P=0.225). Conclusions A PAT-based device provides a reliable AHI in a Japanese patient population, even in patients with CVD. These findings may help reduce the number of patients with undiagnosed SDB and CVD.Background We hypothesized that the intracoronary-electrocardiogram (IC-ECG)-based pressure index would be more stable and precise than the instantaneous flow reserve (iFR). We investigated the usefulness of the IC-ECG-based pressure index for diagnosing myocardial ischemia. Methods and Results Thirty-seven consecutive patients with coronary stenosis requiring physiological assessment were enrolled in the study. iFR was measured at rest and under hyperemia in 51 and 40 lesions, respectively. The IC-ECG-triggered distal pressure (Pd)/aortic pressure (Pa) ratio (ICE-T) was defined as the mean Pd/Pa ratio in the period corresponding to the isoelectric line. The ICE-T was significantly lower than the iFR both at rest and during hyperemia (P less then 0.00001 for both). https://www.selleckchem.com/products/inixaciclib.html Fluctuations in the ICE-T pressure parameters (Pd/Pa, Pa, and Pd) were significantly smaller than those of iFR both at rest and during hyperemia. The diagnostic accuracy of predicting a fractional flow reserve (FFR) ≤0.80 of the ICE-T at rest was significantly higher than that of iFR (P=0.008). Receiver operating characteristic curve analyses showed that the ICE-T predicts FFR ≤0.80 more accurately than the iFR (area under curve 0.897 vs. 0.810 for ICE-T and iFR, respectively). Conclusions We identified the period in the IC-ECG in which resting Pd/Pa was low and constant. The IC-ECG-based algorithm may improve the accuracy of diagnosing myocardial ischemia, without increasing invasiveness, compared with pressure-dependent indices.Background The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF.Background Complete left atrial posterior wall isolation (LAPI) is not always achieved. We examined whether incomplete LAPI has an effect on outcomes after catheter ablation (CA). Methods and Results This study enrolled 75 consecutive patients (mean [±SD] age 62.6±8.9 years, 74.7% male) who underwent LAPI by radiofrequency CA for persistent atrial fibrillation (AF). The median follow-up period was 541 days (interquartile range 338-840 days). Incomplete LAPI was defined as the presence of a successfully created roof or floor linear lesion. The rate of complete LAPI was 41.3% (31/75). Either a roof or floor linear lesion was created in 38 patients, whereas neither was created in 6. Multivariate Cox proportional hazards regression analysis revealed that female sex (hazard ratio [HR] 5.29; 95% confidence interval [CI] 1.81-16.8; P=0.002) and complete or incomplete LAPI (HR 0.17; 95% CI 0.03-0.79; P=0.027) were independent predictors of AF recurrence. Kaplan-Meier curves indicated that better outcome was associated with at least one rather than no successful linear lesion (86.
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  • Using the output signals as a diagnostic marker, we differentiated 33 breast cancer patients from 37 healthy controls with 97.30% sensitivity and 93.94% specificity at the best cutoff. The blood biopsy is simple without extracting plasma exosomes and their nucleic acids content, time-saving in about 2 h of total analysis process, and microvolumes needed for plasma sample, suggesting its good potential to clinical application.An isolable small-molecule cysteine sulfenic acid (Cys-SOH) protected by a molecular cradle was synthesized by direct oxidation of the corresponding cysteine thiol and its structure was established by X-ray crystallographic analysis. Studies on biologically relevant reactivity indicated its usefulness as a biorepresentative small-molecule sulfenic acid model.Van der Waals heterostructures are the fundamental building blocks of electronic and optoelectronic devices. Here we report that, through a single-step chemical vapour deposition (CVD) process, high-quality vertical bilayer MoS2/WS2 heterostructures with a grain size up to ∼60 μm can be synthesized from molten salt precursors, Na2MoO4 and Na2WO4. https://www.selleckchem.com/products/mira-1.html Instead of normal pyramid vertical heterostructures grown by CVD, this method synthesizes an anti-pyramid MoS2/WS2 structure, which is characterized by Raman, photoluminescence and second harmonic generation microscopy. Our facile CVD strategy for synthesizing anti-pyramid structures unveils a new synthesis route for the products of two-dimensional heterostructures and their devices for application.
    With nearly 20% of the US adult population using fitness trackers, there is an increasing focus on how physiological data from these devices can provide actionable insights about workplace performance. However, in-the-wild studies that understand how these metrics correlate with cognitive performance measures across a diverse population are lacking, and claims made by device manufacturers are vague. While there has been extensive research leading to a variety of theories on how physiological measures affect cognitive performance, virtually all such studies have been conducted in highly controlled settings and their validity in the real world is poorly understood.

    We seek to bridge this gap by evaluating prevailing theories on the effects of a variety of sleep, activity, and heart rate parameters on cognitive performance against data collected in real-world settings.

    We used a Fitbit Charge 3 and a smartphone app to collect different physiological and neurobehavioral task data, respectively, as part of ofor more targeted in-the-wild studies investigating how physiological measures from self-tracking data influence, or can be used to predict, specific aspects of cognitive performance.
    Suboptimal adherence to 6-mercaptopurine (6-MP) is prevalent in pediatric acute lymphoblastic leukemia (ALL) and associated with increased risk of relapse. Rapid uptake of personal technology makes mobile health (mHealth) an attractive platform to promote adherence.

    Study objectives were to examine access to mobile technology and preferences for an mHealth intervention to improve medication adherence in pediatric ALL.

    A cross-sectional survey was administered in oncology clinic to parents of children with ALL as well as adolescents and young adults (AYAs) with ALL receiving maintenance chemotherapy.

    A total of 49 parents (median age [IQR] 39 [33-42] years; female 76% [37/49]) and 15 patients (median age [IQR] 17 [16-19]; male 80% [12/15]) participated. All parents and AYAs owned electronic tablets, smartphones, or both. Parents' most endorsed mHealth app features included a list of medications (71%, 35/49), information about 6-MP (71%, 35/49), refill reminders (71%, 35/49), and reminders to take 6-MP (71%, 35/49). AYAs' most endorsed features included refill reminders (73%, 11/15), reminders to take 6-MP (73%, 11/15), and tracking 6-MP (73%, 11/15).

    Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL.
    Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL.
    Psoriasis is an autoimmune disease estimated to affect more than 6 million adults in the United States. It poses a significant public health problem and contributes to rising health care costs, affecting people's quality of life and ability to work. Previous research showed that nontreatment and undertreatment of patients with psoriasis remain a significant problem. Perspectives of patients toward seeking psoriasis treatment are understudied. Social media offers a new data source of user-generated content. Researchers suggested that the social network Twitter may serve as a rich avenue for exploring how patients communicate about their health issues.

    The objective of this study is to conduct a content analysis of Twitter posts (in English) published by users in the United States between February 1, 2016, and October 31, 2018, to examine perspectives that potentially influence the treatment decision among patients with psoriasis.

    User-generated Twitter posts that include keywords related to psoriasis wiloncommercial and will be included in the analysis to assess the patient perspective. Analysis was completed in Summer 2020.

    This protocol paper provides a detailed description of a social media research project including the process of data extraction, cleaning, and analysis. It is our goal to contribute to the development of more transparent social media research efforts. Our findings will shed light on whether Twitter provides a promising data source for garnering patient perspective data about psoriasis treatment decisions. The data will also help to determine whether Twitter might serve as a potential outreach platform for raising awareness of psoriasis and treatment options among patients and implementing related health interventions.

    DERR1-10.2196/13731.
    DERR1-10.2196/13731.
    Using the output signals as a diagnostic marker, we differentiated 33 breast cancer patients from 37 healthy controls with 97.30% sensitivity and 93.94% specificity at the best cutoff. The blood biopsy is simple without extracting plasma exosomes and their nucleic acids content, time-saving in about 2 h of total analysis process, and microvolumes needed for plasma sample, suggesting its good potential to clinical application.An isolable small-molecule cysteine sulfenic acid (Cys-SOH) protected by a molecular cradle was synthesized by direct oxidation of the corresponding cysteine thiol and its structure was established by X-ray crystallographic analysis. Studies on biologically relevant reactivity indicated its usefulness as a biorepresentative small-molecule sulfenic acid model.Van der Waals heterostructures are the fundamental building blocks of electronic and optoelectronic devices. Here we report that, through a single-step chemical vapour deposition (CVD) process, high-quality vertical bilayer MoS2/WS2 heterostructures with a grain size up to ∼60 μm can be synthesized from molten salt precursors, Na2MoO4 and Na2WO4. https://www.selleckchem.com/products/mira-1.html Instead of normal pyramid vertical heterostructures grown by CVD, this method synthesizes an anti-pyramid MoS2/WS2 structure, which is characterized by Raman, photoluminescence and second harmonic generation microscopy. Our facile CVD strategy for synthesizing anti-pyramid structures unveils a new synthesis route for the products of two-dimensional heterostructures and their devices for application. With nearly 20% of the US adult population using fitness trackers, there is an increasing focus on how physiological data from these devices can provide actionable insights about workplace performance. However, in-the-wild studies that understand how these metrics correlate with cognitive performance measures across a diverse population are lacking, and claims made by device manufacturers are vague. While there has been extensive research leading to a variety of theories on how physiological measures affect cognitive performance, virtually all such studies have been conducted in highly controlled settings and their validity in the real world is poorly understood. We seek to bridge this gap by evaluating prevailing theories on the effects of a variety of sleep, activity, and heart rate parameters on cognitive performance against data collected in real-world settings. We used a Fitbit Charge 3 and a smartphone app to collect different physiological and neurobehavioral task data, respectively, as part of ofor more targeted in-the-wild studies investigating how physiological measures from self-tracking data influence, or can be used to predict, specific aspects of cognitive performance. Suboptimal adherence to 6-mercaptopurine (6-MP) is prevalent in pediatric acute lymphoblastic leukemia (ALL) and associated with increased risk of relapse. Rapid uptake of personal technology makes mobile health (mHealth) an attractive platform to promote adherence. Study objectives were to examine access to mobile technology and preferences for an mHealth intervention to improve medication adherence in pediatric ALL. A cross-sectional survey was administered in oncology clinic to parents of children with ALL as well as adolescents and young adults (AYAs) with ALL receiving maintenance chemotherapy. A total of 49 parents (median age [IQR] 39 [33-42] years; female 76% [37/49]) and 15 patients (median age [IQR] 17 [16-19]; male 80% [12/15]) participated. All parents and AYAs owned electronic tablets, smartphones, or both. Parents' most endorsed mHealth app features included a list of medications (71%, 35/49), information about 6-MP (71%, 35/49), refill reminders (71%, 35/49), and reminders to take 6-MP (71%, 35/49). AYAs' most endorsed features included refill reminders (73%, 11/15), reminders to take 6-MP (73%, 11/15), and tracking 6-MP (73%, 11/15). Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL. Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL. Psoriasis is an autoimmune disease estimated to affect more than 6 million adults in the United States. It poses a significant public health problem and contributes to rising health care costs, affecting people's quality of life and ability to work. Previous research showed that nontreatment and undertreatment of patients with psoriasis remain a significant problem. Perspectives of patients toward seeking psoriasis treatment are understudied. Social media offers a new data source of user-generated content. Researchers suggested that the social network Twitter may serve as a rich avenue for exploring how patients communicate about their health issues. The objective of this study is to conduct a content analysis of Twitter posts (in English) published by users in the United States between February 1, 2016, and October 31, 2018, to examine perspectives that potentially influence the treatment decision among patients with psoriasis. User-generated Twitter posts that include keywords related to psoriasis wiloncommercial and will be included in the analysis to assess the patient perspective. Analysis was completed in Summer 2020. This protocol paper provides a detailed description of a social media research project including the process of data extraction, cleaning, and analysis. It is our goal to contribute to the development of more transparent social media research efforts. Our findings will shed light on whether Twitter provides a promising data source for garnering patient perspective data about psoriasis treatment decisions. The data will also help to determine whether Twitter might serve as a potential outreach platform for raising awareness of psoriasis and treatment options among patients and implementing related health interventions. DERR1-10.2196/13731. DERR1-10.2196/13731.
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  • The genus Trypanosoma includes flagellated protozoa belonging to the family Trypanosomatidae (Euglenozoa, Kinetoplastida) that can infect humans and several animal species. The most studied species are those causing severe human pathology, such as Chagas disease in South and Central America, and the human African trypanosomiasis (HAT), or infections highly affecting animal health, such as nagana in Africa and surra with a wider geographical distribution. The presence of these Trypanosoma species in Europe has been thus far linked only to travel/immigration history of the human patients or introduction of infected animals. On the contrary, little is known about the epidemiological status of trypanosomes endemically infecting mammals in Europe, such as Trypanosomatheileri in ruminants and Trypanosomalewisi in rodents and other sporadically reported species. This brief review provides an updated collection of scientific data on the presence of autochthonous Trypanosoma spp. in mammals on the European territory, in order to support epidemiological and diagnostic studies on Trypanosomatid parasites.An iris-claw intraocular lens (IOL) has been widely used as a secondary implant in aphakic patients. The study presents the results of implanting the anterior chamber iris-claw Artisan IOL in cases of where an appropriate posterior capsular support is lacking. The study included 132 patients subjected to primary IOL implantation during complicated cataract surgery with damage to the posterior capsule (I), secondary implantation in aphakia (II), secondary implantation during penetrating keratoplasty (III), and secondary implantation during pars plana vitrectomy with luxated IOL extraction (IV). We analyzed the records of best-corrected visual acuity (BCVA), spherical equivalent (SE), intraocular pressure (IOP), and corneal endothelial cell count (cECC), taken before and 1, 2, 3, and 4 years after the surgery. BCVA depended on the time after IOL implantation and the primary indication. Four years post-surgery, the SE values were the lowest in group III. IOP was the same in all groups both before and after the surgery, but 4 years after the surgery IOP values in group IV were higher than in group III. The cECC decreased every year after the surgery in all groups, but four years after the IOL implantation, the lowest cECC values were observed in group IV. At the same time, all groups of patients showed improved BCVA, stable refraction, and a low percentage of postoperative complications.The human body is exposed to oxidative damage to cells and though it has some endogenous antioxidant systems, we still need to take antioxidants from our diet. The main dietary source of antioxidants is vegetables due to their content of different bioactive molecules. However, there are usually other components of the diet, such as foods of animal origin, that are not often linked to antioxidant capacity. Still, these foods are bound to exert some antioxidant capacity thanks to molecules released during gastrointestinal digestion and gut microbial fermentation. In this work, the antioxidant capacity of 11 foods of animal origin has been studied, submitted to different culinary techniques and to an in vitro digestion and gut microbial fermentation. Results have shown how dairy products potentially provide the highest antioxidant capacity, contributing to 60% of the daily antioxidant capacity intake. On the other hand, most of the antioxidant capacity was released during gut microbial fermentation (90-98% of the total antioxidant capacity). Finally, it was found that the antioxidant capacity of the studied foods was **** higher than that reported by other authors. A possible explanation is that digestion-fermentation pretreatment allows for a higher extraction of antioxidant compounds and their transformation by the gut microbiota. Therefore, although foods of animal origin cannot be compared to vegetables in the concentration of antioxidant molecules, the processes of digestion and fermentation can provide some, giving animal origin food some qualities that could have been previously unappreciated.Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. https://www.selleckchem.com/products/methylene-blue-trihydrate.html This article reviews the relevance of PI3K signaling and pharmacologic inhibition in CLL. Data on efficacy and toxicity of PI3K inhibitors are also presented, as well as strategies for overcoming barriers for their clinical use in CLL treatment.Clostridium perfringens is a Gram-positive bacterium that possess seven toxinotypes (A, B, C, D, E, F, and G) that are responsible for the production of six major toxins, i.e., α, β, ε, ι, CPE, and NetB. The aim of this study is to find out the occurrence of toxinotypes in buffalo and cattle of Punjab province in Pakistan and their corresponding toxin-encoding genes from the isolated toxinotypes. To accomplish this aim, six districts in Punjab province were selected (i.e., Lahore, Sahiwal, Cheecha Watni, Bhakkar, Dera Ghazi Khan, and Bahawalpur) and a total of 240 buffalo and 240 cattle were selected for the collection of samples. From isolation and molecular analysis (16S rRNA), it was observed that out of seven toxinotypes (A-G), two toxinotypes (A and D) were found at most, whereas other toxinotypes, i.e., B, C, E, F, and G, were not found. The most frequently occurring toxinotype was type A (buffalo 149/240; cattle 157/240) whereas type D (buffalo 8/240 cattle 7/240) was found to occur the least. Genes encoding toxinotypes A and D were cpa and etx, respectively, whereas genes encoding other toxinotypes were not observed. The occurrence of isolated toxinotypes was studied using response surface methodology, which suggested a considerable occurrence of the isolated toxinotypes (A and D) in both buffalo and cattle. Association between type A and type D was found to be significant among the isolated toxinotypes in both buffalo and cattle (p ≤ 0.05). Correlation was also found to be positive and significant between type A and type D. C. perfringens exhibits a range of toxinotypes that can be diagnosed via genotyping, which is more reliable than classical toxinotyping.
    The genus Trypanosoma includes flagellated protozoa belonging to the family Trypanosomatidae (Euglenozoa, Kinetoplastida) that can infect humans and several animal species. The most studied species are those causing severe human pathology, such as Chagas disease in South and Central America, and the human African trypanosomiasis (HAT), or infections highly affecting animal health, such as nagana in Africa and surra with a wider geographical distribution. The presence of these Trypanosoma species in Europe has been thus far linked only to travel/immigration history of the human patients or introduction of infected animals. On the contrary, little is known about the epidemiological status of trypanosomes endemically infecting mammals in Europe, such as Trypanosomatheileri in ruminants and Trypanosomalewisi in rodents and other sporadically reported species. This brief review provides an updated collection of scientific data on the presence of autochthonous Trypanosoma spp. in mammals on the European territory, in order to support epidemiological and diagnostic studies on Trypanosomatid parasites.An iris-claw intraocular lens (IOL) has been widely used as a secondary implant in aphakic patients. The study presents the results of implanting the anterior chamber iris-claw Artisan IOL in cases of where an appropriate posterior capsular support is lacking. The study included 132 patients subjected to primary IOL implantation during complicated cataract surgery with damage to the posterior capsule (I), secondary implantation in aphakia (II), secondary implantation during penetrating keratoplasty (III), and secondary implantation during pars plana vitrectomy with luxated IOL extraction (IV). We analyzed the records of best-corrected visual acuity (BCVA), spherical equivalent (SE), intraocular pressure (IOP), and corneal endothelial cell count (cECC), taken before and 1, 2, 3, and 4 years after the surgery. BCVA depended on the time after IOL implantation and the primary indication. Four years post-surgery, the SE values were the lowest in group III. IOP was the same in all groups both before and after the surgery, but 4 years after the surgery IOP values in group IV were higher than in group III. The cECC decreased every year after the surgery in all groups, but four years after the IOL implantation, the lowest cECC values were observed in group IV. At the same time, all groups of patients showed improved BCVA, stable refraction, and a low percentage of postoperative complications.The human body is exposed to oxidative damage to cells and though it has some endogenous antioxidant systems, we still need to take antioxidants from our diet. The main dietary source of antioxidants is vegetables due to their content of different bioactive molecules. However, there are usually other components of the diet, such as foods of animal origin, that are not often linked to antioxidant capacity. Still, these foods are bound to exert some antioxidant capacity thanks to molecules released during gastrointestinal digestion and gut microbial fermentation. In this work, the antioxidant capacity of 11 foods of animal origin has been studied, submitted to different culinary techniques and to an in vitro digestion and gut microbial fermentation. Results have shown how dairy products potentially provide the highest antioxidant capacity, contributing to 60% of the daily antioxidant capacity intake. On the other hand, most of the antioxidant capacity was released during gut microbial fermentation (90-98% of the total antioxidant capacity). Finally, it was found that the antioxidant capacity of the studied foods was much higher than that reported by other authors. A possible explanation is that digestion-fermentation pretreatment allows for a higher extraction of antioxidant compounds and their transformation by the gut microbiota. Therefore, although foods of animal origin cannot be compared to vegetables in the concentration of antioxidant molecules, the processes of digestion and fermentation can provide some, giving animal origin food some qualities that could have been previously unappreciated.Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. https://www.selleckchem.com/products/methylene-blue-trihydrate.html This article reviews the relevance of PI3K signaling and pharmacologic inhibition in CLL. Data on efficacy and toxicity of PI3K inhibitors are also presented, as well as strategies for overcoming barriers for their clinical use in CLL treatment.Clostridium perfringens is a Gram-positive bacterium that possess seven toxinotypes (A, B, C, D, E, F, and G) that are responsible for the production of six major toxins, i.e., α, β, ε, ι, CPE, and NetB. The aim of this study is to find out the occurrence of toxinotypes in buffalo and cattle of Punjab province in Pakistan and their corresponding toxin-encoding genes from the isolated toxinotypes. To accomplish this aim, six districts in Punjab province were selected (i.e., Lahore, Sahiwal, Cheecha Watni, Bhakkar, Dera Ghazi Khan, and Bahawalpur) and a total of 240 buffalo and 240 cattle were selected for the collection of samples. From isolation and molecular analysis (16S rRNA), it was observed that out of seven toxinotypes (A-G), two toxinotypes (A and D) were found at most, whereas other toxinotypes, i.e., B, C, E, F, and G, were not found. The most frequently occurring toxinotype was type A (buffalo 149/240; cattle 157/240) whereas type D (buffalo 8/240 cattle 7/240) was found to occur the least. Genes encoding toxinotypes A and D were cpa and etx, respectively, whereas genes encoding other toxinotypes were not observed. The occurrence of isolated toxinotypes was studied using response surface methodology, which suggested a considerable occurrence of the isolated toxinotypes (A and D) in both buffalo and cattle. Association between type A and type D was found to be significant among the isolated toxinotypes in both buffalo and cattle (p ≤ 0.05). Correlation was also found to be positive and significant between type A and type D. C. perfringens exhibits a range of toxinotypes that can be diagnosed via genotyping, which is more reliable than classical toxinotyping.
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