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atients.Level of Evidence 3.
Baseline pain duration would appear to be of clinical importance. Patients with shorter baseline pain duration demonstrated better outcomes. Those with ≥12 month's duration of pain may need additional support during their management to achieve clinically relevant functional improvements in the medium-to-long term. These findings raise questions about the decision by NICE to move away from duration of pain to differentiate management of LBP patients.Level of Evidence 3.
A retrospective study.
The aim of this study was to investigate the relationship between thoracic morphology (TM) and pulmonary function (PF) in patients with adolescent idiopathic scoliosis (AIS) and the feasibility of the "apical vertebra deviation ratio (AVDR)" as a predictor of PF impairment.
The PF of AIS is one of the key focuses of clinicians' attention. Early identification of AIS patients who are at risk of developing impaired PF is important for improving patient management.
Preoperative PF and radiographic examination data of 108 patients with thoracic AIS were collected. The following TM data were collected the costophrenic angle distance (***), distance between T1 and mean diaphragm height (T1-diaphragm), T1-T12 height, and AVDR. The correlation coefficient between PF and TM measurements was analyzed, and univariable and multivariable linear regressions were used to determine whether the TM measurements could predict PF.
The ***, T1-diaphragm, and T1-T12 height were significantly positient may suffer from moderate or severe PF damage.Level of Evidence 4.
Retrospective study.
To elucidate an association between preoperative lumbar epidural corticosteroid injections (ESI) and infection after lumbar spine surgery.
ESI may provide diagnostic and therapeutic benefit; however, concern exists regarding whether preoperative ESI may increase risk of postoperative infection.
Patients who underwent lumbar decompression alone or fusion procedures for radiculopathy or stenosis between 2000 and 2017 with 90 days follow-up were identified by ICD/CPT codes. https://www.selleckchem.com/ Each cohort was categorized as no preoperative ESI, less than 30 days, 30 to 90 days, and greater than 90 days before surgery. The primary outcome measure was postoperative infection requiring reoperation within 90 days of index procedure. Demographic information including age, sex, body mass index (BMI), Charlson Comorbidity Index (CCI) was determined. Comparison and regression analysis was performed to determine an association between preoperative ESI exposure, demographics/comorbidities, and postoperative infecf infection was found in patients with preoperative ESI undergoing fusion procedures, but no increased risk with decompression only. Fusion, BMI, and CCI were predictors of postoperative infection.Level of Evidence 3.
An increased risk of infection was found in patients with preoperative ESI undergoing fusion procedures, but no increased risk with decompression only. Fusion, BMI, and CCI were predictors of postoperative infection.Level of Evidence 3.
Retrospective chart review.
The aim of this study was to ascertain whether the presence of structural thoracic deformities affects outcomes of permanent SCS placement.
Neural modulation via spinal cord stimulators (SCSs) has become an accepted treatment option for various chronic pain syndromes. In most cases, the surgeon desires accurate midline positioning of the paddle lead, allowing for flexibility of unilateral or bilateral coverage of pain patterns. Structural spinal deformities (scoliosis or kyphosis) often result from coronal, sagittal, and rotatory deformity that can make midline placement more difficult.
Between 2013 and 2017, two-hundred forty-one charts of patients who underwent permanent SCS placement at our suburban hospital were reviewed. Demographic information, numerical rating system (NRS) pain scores, Oswestry Disability Index (ODI) scores, and opioid medication usage were recorded at baseline and after permanent stimulator placement. Thoracic scoliosis and kyphosis angles were measCS placement and as such should not preclude this population from benefiting from such therapies.Level of Evidence 4.
SCSs can be effective options for treating lumbar **** pain and radiculopathy. Our study suggests that the presence of mild structural deformities does not adversely affect outcomes of permanent SCS placement and as such should not preclude this population from benefiting from such therapies.Level of Evidence 4.
A retrospective cohort study.
The aim of this study was to identify an association between preoperative opioid use and reoperations rates.
Chronic opioid use is a public health crisis in the United States and has been linked to worse outcomes after lumbar spine surgery. However, no studies have identified an association between preoperative opioid use and reoperations rates.
A retrospective cohort study was conducted using patients from one private insurance database who underwent primary lumbar decompression/discectomy (LDD) or posterior/transforaminal lumbar interbody fusion (PLIF/TLIF). Preoperative use of five specific opioid medications (tramadol, hydromorphone, oxycodone, hydromorphone, and extended-release oxycodone) was categorized as acute (within 3 months), subacute (acute use and use between 3 and 6 months), or chronic (subacute use and use before 6 months). Multivariate regression, controlling for multilevel surgery, age, sex, and Charlson Comorbidity Index, was used to determine the assocchronic use; P < 0.05).
Preoperative use of the higher-potency opioid medications is associated with increased reoperations after LDD and PLIF/TLIF in a dose-dependent manner. Surgeons should use this data for preoperative opioid cessation counseling and individualized risk stratification.Level of Evidence 3.
Preoperative use of the higher-potency opioid medications is associated with increased reoperations after LDD and PLIF/TLIF in a dose-dependent manner. Surgeons should use this data for preoperative opioid cessation counseling and individualized risk stratification.Level of Evidence 3.
atients.Level of Evidence 3. Baseline pain duration would appear to be of clinical importance. Patients with shorter baseline pain duration demonstrated better outcomes. Those with ≥12 month's duration of pain may need additional support during their management to achieve clinically relevant functional improvements in the medium-to-long term. These findings raise questions about the decision by NICE to move away from duration of pain to differentiate management of LBP patients.Level of Evidence 3. A retrospective study. The aim of this study was to investigate the relationship between thoracic morphology (TM) and pulmonary function (PF) in patients with adolescent idiopathic scoliosis (AIS) and the feasibility of the "apical vertebra deviation ratio (AVDR)" as a predictor of PF impairment. The PF of AIS is one of the key focuses of clinicians' attention. Early identification of AIS patients who are at risk of developing impaired PF is important for improving patient management. Preoperative PF and radiographic examination data of 108 patients with thoracic AIS were collected. The following TM data were collected the costophrenic angle distance (CAD), distance between T1 and mean diaphragm height (T1-diaphragm), T1-T12 height, and AVDR. The correlation coefficient between PF and TM measurements was analyzed, and univariable and multivariable linear regressions were used to determine whether the TM measurements could predict PF. The CAD, T1-diaphragm, and T1-T12 height were significantly positient may suffer from moderate or severe PF damage.Level of Evidence 4. Retrospective study. To elucidate an association between preoperative lumbar epidural corticosteroid injections (ESI) and infection after lumbar spine surgery. ESI may provide diagnostic and therapeutic benefit; however, concern exists regarding whether preoperative ESI may increase risk of postoperative infection. Patients who underwent lumbar decompression alone or fusion procedures for radiculopathy or stenosis between 2000 and 2017 with 90 days follow-up were identified by ICD/CPT codes. https://www.selleckchem.com/ Each cohort was categorized as no preoperative ESI, less than 30 days, 30 to 90 days, and greater than 90 days before surgery. The primary outcome measure was postoperative infection requiring reoperation within 90 days of index procedure. Demographic information including age, sex, body mass index (BMI), Charlson Comorbidity Index (CCI) was determined. Comparison and regression analysis was performed to determine an association between preoperative ESI exposure, demographics/comorbidities, and postoperative infecf infection was found in patients with preoperative ESI undergoing fusion procedures, but no increased risk with decompression only. Fusion, BMI, and CCI were predictors of postoperative infection.Level of Evidence 3. An increased risk of infection was found in patients with preoperative ESI undergoing fusion procedures, but no increased risk with decompression only. Fusion, BMI, and CCI were predictors of postoperative infection.Level of Evidence 3. Retrospective chart review. The aim of this study was to ascertain whether the presence of structural thoracic deformities affects outcomes of permanent SCS placement. Neural modulation via spinal cord stimulators (SCSs) has become an accepted treatment option for various chronic pain syndromes. In most cases, the surgeon desires accurate midline positioning of the paddle lead, allowing for flexibility of unilateral or bilateral coverage of pain patterns. Structural spinal deformities (scoliosis or kyphosis) often result from coronal, sagittal, and rotatory deformity that can make midline placement more difficult. Between 2013 and 2017, two-hundred forty-one charts of patients who underwent permanent SCS placement at our suburban hospital were reviewed. Demographic information, numerical rating system (NRS) pain scores, Oswestry Disability Index (ODI) scores, and opioid medication usage were recorded at baseline and after permanent stimulator placement. Thoracic scoliosis and kyphosis angles were measCS placement and as such should not preclude this population from benefiting from such therapies.Level of Evidence 4. SCSs can be effective options for treating lumbar back pain and radiculopathy. Our study suggests that the presence of mild structural deformities does not adversely affect outcomes of permanent SCS placement and as such should not preclude this population from benefiting from such therapies.Level of Evidence 4. A retrospective cohort study. The aim of this study was to identify an association between preoperative opioid use and reoperations rates. Chronic opioid use is a public health crisis in the United States and has been linked to worse outcomes after lumbar spine surgery. However, no studies have identified an association between preoperative opioid use and reoperations rates. A retrospective cohort study was conducted using patients from one private insurance database who underwent primary lumbar decompression/discectomy (LDD) or posterior/transforaminal lumbar interbody fusion (PLIF/TLIF). Preoperative use of five specific opioid medications (tramadol, hydromorphone, oxycodone, hydromorphone, and extended-release oxycodone) was categorized as acute (within 3 months), subacute (acute use and use between 3 and 6 months), or chronic (subacute use and use before 6 months). Multivariate regression, controlling for multilevel surgery, age, sex, and Charlson Comorbidity Index, was used to determine the assocchronic use; P < 0.05). Preoperative use of the higher-potency opioid medications is associated with increased reoperations after LDD and PLIF/TLIF in a dose-dependent manner. Surgeons should use this data for preoperative opioid cessation counseling and individualized risk stratification.Level of Evidence 3. Preoperative use of the higher-potency opioid medications is associated with increased reoperations after LDD and PLIF/TLIF in a dose-dependent manner. Surgeons should use this data for preoperative opioid cessation counseling and individualized risk stratification.Level of Evidence 3.0 Kommentare 0 Geteilt 1 Ansichten 0 BewertungenBitte loggen Sie sich ein, um liken, teilen und zu kommentieren! -
Although endocrinologic involvement and epilepsy are frequent features of myoclonic epilepsy with ragged-red fibers (MERRF), polycystic ovary syndrome (PCOS) and photosensitive epilepsy have not been reported.
. A 32-year-old female was diagnosed with MERRF at age 19 y upon presence of the four canonical features and the variant m.8344A > G in
(
) (blood heteroplasmy rate 50%). She experienced recurrent photosensitive focal and generalised seizures since age 19 y, which could be triggered by flickering light or by looking at small stones, leaves, or dirty snow on the ground. Since the last 42 months, she was seizure-free upon levetiracetam (4000 mg/d), clonazepam (1.5 mg/d), and topiramate (25 mg/d). Additionally, she suffered from secondary amenorrhoea since adolescence. She was married between ages 19 y and 25 y but did not get pregnant. PCOS was diagnosed and treated with desogestrel plus estradiol. Nonetheless, the course was progressive, particularly with regard to ataxia, myocloni, and myopathy.
The phenotypic spectrum of MERRF is broader than anticipated and may additionally include PCOS and photosensitive epilepsy. PCOS in MERRF may respond to hormone substitution and photosensitive epilepsy to levetiracetam, clonazepam, and topiramate.
The phenotypic spectrum of MERRF is broader than anticipated and may additionally include PCOS and photosensitive epilepsy. PCOS in MERRF may respond to hormone substitution and photosensitive epilepsy to levetiracetam, clonazepam, and topiramate.Colorectal cancer (CRC) is the third most diagnosed cancer in the United States, and many patients unfortunately have metastases at the time of their diagnosis. Cutaneous metastases of CRC have been reported in few journals and primarily as case reports due to their rarity. Here, we present the case of an 83-year-old woman with recently resected colon cancer, T4aN1bMx stage IIIB. She presented to our clinic for evaluation of a right midback mass, and a punch biopsy revealed dermal involvement by invasive, poorly differentiated carcinoma with epidermoid features. The mass was excised, and we ordered a PET scan in search of the primary tumor, which at that time was suspected to be of skin cancer origin. Surprisingly, this revealed a second malignancy triple-negative invasive ductal carcinoma of the left breast. The **** mass stained positive for CK20, which was compatible with a metastasis from a colonic primary. After initially declining adjuvant therapy, the patient completed one cycle of capecitabine and oxaliplatin, which she tolerated poorly. She continued to further decline, developed widespread cutaneous metastases, and went home on hospice. Cutaneous lesions are an exceedingly rare site of metastasis for colon adenocarcinoma, and their clinical presentation can vary widely. It is important for providers to investigate any new skin lesion in a patient with a recent or remote history of malignancy, even if there were no sites of distant metastasis at initial diagnosis.Hepatocellular carcinoma (HCC) is the most common primary liver cancer and can arise from any form of chronic liver disease or cirrhosis. With increasing rates of metabolic syndrome and obesity, it is not surprising that NASH is quickly becoming a leading cause of chronic liver disease and HCC in the western hemisphere (Wang and Malhi, 2018). Metastasis is usually found in advanced stages of the disease, owing to its poor prognosis. The lung, bone, and lymph nodes are the most frequent sites of metastasis (Balogh et al., 2016, and Becker et al., 2014). On the other hand, metastasis to the skin and cranium is relatively rare. Literature review reveals less than 10 reported cases in the last 10 years. Herein, we report an unusual case of a "forehead hematoma" leading to the formal diagnosis of metastatic HCC.Pheochromocytomas are tumors that originate from the chromaffin tissue of the adrenal medulla and commonly produce catecholamines. The diagnosis is typically established by the measurement of catecholamines or their metabolites in urine or plasma, and tumors are localized with the use of radiographic and scintigraphic studies. Pheochromocytomas can occur in asymptomatic patients, and the preferred treatment is surgical removal of the tumor. We report a 48-year-old male with a left adrenal incidentaloma, which progressively increased in size from 1.1 cm to 2.6 cm over a 4-year period, as measured by an adrenal computed tomography (CT) scan. Throughout his entire course of treatment, he was asymptomatic with normal blood pressure readings. His biochemical screening was unremarkable for the first three years of tumor surveillance. Follow-up imaging, including CT and MRI, showed findings suspicious for pheochromocytoma, and the diagnosis was ultimately made with the combination of imaging and laboratory studies. He underwent laparoscopic resection of the adrenal mass with confirmation of pheochromocytoma on histology. This case illustrates how CT and MRI findings can alert providers to the presence of a pheochromocytoma, even in an asymptomatic, biochemically negative patient.Adrenocortical oncocytomas are rare and mostly nonfunctioning neoplasms. We report the case of a 27-year-old woman diagnosed with an ACTH-independent Cushing's syndrome due to left adrenal oncocytoma. She underwent laparoscopic adrenalectomy. Histopathological examination revealed an oncocytoma of uncertain malignant potential with a low Ki-67 proliferation index, inhibin A positivity, and chromogranin A negativity. Electron micrographs confirmed adrenal oncocytoma cells, characterized by the presence of a large amount of mitochondria. The postoperative course was uneventful, and the patient experienced a progressive regression of Cushing-related symptoms. Periodical follow-ups with MRI and cortisol dosage are required due to the neoplasm's uncertain malignant potential. Considerations on the diagnosis, pathology findings, clinical remarks, and interventions are made.Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) gene but also AP2S1 and GNA11 genes, which encode for adaptor-related protein complex 2 and G11 proteins, respectively. The manifestations of FHH can vary and sometimes overlap with primary hyperparathyroidism making the diagnosis challenging. https://www.selleckchem.com/JAK.html Case Presentations. We report a mother and daughter with a novel heterozygous variant in the CaSR gene resulting in a serine to leucine substitution at position 147 (S147L) of the CaSR. Both patients had mild hypercalcemia, relatively low urinary calcium excretion, elevated calcitriol, and low-to-normal intact PTH. The proband (daughter) presented with symptoms associated with hypercalcemia and was incidentally found to have a bony lesion suspicious for osteitis fibrosa cystica, and she was also diagnosed with sarcoidosis.
Although endocrinologic involvement and epilepsy are frequent features of myoclonic epilepsy with ragged-red fibers (MERRF), polycystic ovary syndrome (PCOS) and photosensitive epilepsy have not been reported. . A 32-year-old female was diagnosed with MERRF at age 19 y upon presence of the four canonical features and the variant m.8344A > G in ( ) (blood heteroplasmy rate 50%). She experienced recurrent photosensitive focal and generalised seizures since age 19 y, which could be triggered by flickering light or by looking at small stones, leaves, or dirty snow on the ground. Since the last 42 months, she was seizure-free upon levetiracetam (4000 mg/d), clonazepam (1.5 mg/d), and topiramate (25 mg/d). Additionally, she suffered from secondary amenorrhoea since adolescence. She was married between ages 19 y and 25 y but did not get pregnant. PCOS was diagnosed and treated with desogestrel plus estradiol. Nonetheless, the course was progressive, particularly with regard to ataxia, myocloni, and myopathy. The phenotypic spectrum of MERRF is broader than anticipated and may additionally include PCOS and photosensitive epilepsy. PCOS in MERRF may respond to hormone substitution and photosensitive epilepsy to levetiracetam, clonazepam, and topiramate. The phenotypic spectrum of MERRF is broader than anticipated and may additionally include PCOS and photosensitive epilepsy. PCOS in MERRF may respond to hormone substitution and photosensitive epilepsy to levetiracetam, clonazepam, and topiramate.Colorectal cancer (CRC) is the third most diagnosed cancer in the United States, and many patients unfortunately have metastases at the time of their diagnosis. Cutaneous metastases of CRC have been reported in few journals and primarily as case reports due to their rarity. Here, we present the case of an 83-year-old woman with recently resected colon cancer, T4aN1bMx stage IIIB. She presented to our clinic for evaluation of a right midback mass, and a punch biopsy revealed dermal involvement by invasive, poorly differentiated carcinoma with epidermoid features. The mass was excised, and we ordered a PET scan in search of the primary tumor, which at that time was suspected to be of skin cancer origin. Surprisingly, this revealed a second malignancy triple-negative invasive ductal carcinoma of the left breast. The back mass stained positive for CK20, which was compatible with a metastasis from a colonic primary. After initially declining adjuvant therapy, the patient completed one cycle of capecitabine and oxaliplatin, which she tolerated poorly. She continued to further decline, developed widespread cutaneous metastases, and went home on hospice. Cutaneous lesions are an exceedingly rare site of metastasis for colon adenocarcinoma, and their clinical presentation can vary widely. It is important for providers to investigate any new skin lesion in a patient with a recent or remote history of malignancy, even if there were no sites of distant metastasis at initial diagnosis.Hepatocellular carcinoma (HCC) is the most common primary liver cancer and can arise from any form of chronic liver disease or cirrhosis. With increasing rates of metabolic syndrome and obesity, it is not surprising that NASH is quickly becoming a leading cause of chronic liver disease and HCC in the western hemisphere (Wang and Malhi, 2018). Metastasis is usually found in advanced stages of the disease, owing to its poor prognosis. The lung, bone, and lymph nodes are the most frequent sites of metastasis (Balogh et al., 2016, and Becker et al., 2014). On the other hand, metastasis to the skin and cranium is relatively rare. Literature review reveals less than 10 reported cases in the last 10 years. Herein, we report an unusual case of a "forehead hematoma" leading to the formal diagnosis of metastatic HCC.Pheochromocytomas are tumors that originate from the chromaffin tissue of the adrenal medulla and commonly produce catecholamines. The diagnosis is typically established by the measurement of catecholamines or their metabolites in urine or plasma, and tumors are localized with the use of radiographic and scintigraphic studies. Pheochromocytomas can occur in asymptomatic patients, and the preferred treatment is surgical removal of the tumor. We report a 48-year-old male with a left adrenal incidentaloma, which progressively increased in size from 1.1 cm to 2.6 cm over a 4-year period, as measured by an adrenal computed tomography (CT) scan. Throughout his entire course of treatment, he was asymptomatic with normal blood pressure readings. His biochemical screening was unremarkable for the first three years of tumor surveillance. Follow-up imaging, including CT and MRI, showed findings suspicious for pheochromocytoma, and the diagnosis was ultimately made with the combination of imaging and laboratory studies. He underwent laparoscopic resection of the adrenal mass with confirmation of pheochromocytoma on histology. This case illustrates how CT and MRI findings can alert providers to the presence of a pheochromocytoma, even in an asymptomatic, biochemically negative patient.Adrenocortical oncocytomas are rare and mostly nonfunctioning neoplasms. We report the case of a 27-year-old woman diagnosed with an ACTH-independent Cushing's syndrome due to left adrenal oncocytoma. She underwent laparoscopic adrenalectomy. Histopathological examination revealed an oncocytoma of uncertain malignant potential with a low Ki-67 proliferation index, inhibin A positivity, and chromogranin A negativity. Electron micrographs confirmed adrenal oncocytoma cells, characterized by the presence of a large amount of mitochondria. The postoperative course was uneventful, and the patient experienced a progressive regression of Cushing-related symptoms. Periodical follow-ups with MRI and cortisol dosage are required due to the neoplasm's uncertain malignant potential. Considerations on the diagnosis, pathology findings, clinical remarks, and interventions are made.Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) gene but also AP2S1 and GNA11 genes, which encode for adaptor-related protein complex 2 and G11 proteins, respectively. The manifestations of FHH can vary and sometimes overlap with primary hyperparathyroidism making the diagnosis challenging. https://www.selleckchem.com/JAK.html Case Presentations. We report a mother and daughter with a novel heterozygous variant in the CaSR gene resulting in a serine to leucine substitution at position 147 (S147L) of the CaSR. Both patients had mild hypercalcemia, relatively low urinary calcium excretion, elevated calcitriol, and low-to-normal intact PTH. The proband (daughter) presented with symptoms associated with hypercalcemia and was incidentally found to have a bony lesion suspicious for osteitis fibrosa cystica, and she was also diagnosed with sarcoidosis.0 Kommentare 0 Geteilt 0 Ansichten 0 Bewertungen -
Hospitalized patients with COVID-19 are at high risk for anxiety and depression, but most studies about mental health during the pandemic included the general public, healthcare workers, and students. We aimed to explore the anxiety and depression levels, prevalence and predictors in patients hospitalized with COVID-19.
In this cross-sectional, exploratory study, sociodemographic and clinical features of 281 patients with confirmed COVID-19 were explored. Patients underwent a comprehensive psychiatric assessment and the Hospital Anxiety and Depression Scale (HADS) was administered through a telephonic interview.
The mean age of the participants was 55.0 ± 14.9 years. One hundred forty-three (50.9%) patients were male, and 138 (49.1%) were female. Ninety-eight (34.9%) patients had significant levels of anxiety and 118 (42.0%) had significant levels of depression. Female gender, staying alone in a hospital room, early days of hospital stay, and any lifetime psychiatric disorder was associated with symptoms of anxiety. Being over 50 years of age, staying alone in a hospital room, and NSAID use before the week of hospital admission were associated with symptoms of depression. https://www.selleckchem.com/products/ide397-gsk-4362676.html Anxiety and depression levels were lower when family members who tested positive for COVID-19 stayed in the same hospital room during treatment.
Women, patients >50 years, patients who used NSAIDs before hospital admission, and those with lifetime psychiatric disorders may be at risk for anxiety and depressive symptoms in the COVID-19 ward. Allowing family members with COVID-19 to stay in the same hospital room may be associated with lower anxiety and depression levels.
50 years, patients who used NSAIDs before hospital admission, and those with lifetime psychiatric disorders may be at risk for anxiety and depressive symptoms in the COVID-19 ward. Allowing family members with COVID-19 to stay in the same hospital room may be associated with lower anxiety and depression levels.For a definite indication for immunotherapy, finding appropriate biomarkers that are predictive of treatment responses is necessary. Inflammatory cytokines which play critical roles in immunity against infectious sources or cancer cells are suggested to activate immune cells after initiation of immune checkpoint inhibitors (ICI). Through activation of immune cells such as T cells, natural killer cells, macrophages, or tumor infiltrating dendritic cells, inflammatory cytokines usually increase after programmed death (PD)-1/PD-L1 axis blockade. There have been several studies evaluating the predictive value of early changes in inflammatory cytokines in non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. In this mini-review, we went through recent articles on potential blood level values of inflammatory cytokines in NSCLC patients receiving ICI and their early change around commencement of ICIs in predicting response to treatment and disease progression. The studies evaluated cytokines including interleukin (IL)-2, 6, 8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for predictability for responses to ICI. A combination cytokine panel can help predict the response and prognosis of patients with NSCLC who are receiving ICI treatment. Furthermore, a more individualized ICI treatment will be available if responses and change in tumor burden can be predicted. However, most of the studies on cytokines in NSCLC patients receiving ICIs had a small number of patients, and the heterogeneous measurement time points. Nevertheless, cytokines such as IL-8 and IFN- γ have considerable potential predictive value for immunotherapy response, which is worthy of further studies. To utilize blood cytokines levels as biomarkers for immunotherapy, a larger study with uniform measurement protocol is necessary.
The pregnancy period represents the most intense period of growth and development. Pre-pregnancy weight influences weight gain during pregnancy. Leptin is a hormone mainly derived from white adipose tissue, during pregnancy leptin is also produced by the placenta. It has been suggested that the effects of placental leptin on the mother may contribute to endocrine-mediated alterations in energy balance; a dysregulation in leptin levels or its receptors may lead to poor birth outcomes. Therefore, the main goal of the present study was to analyze the differences in birth outcomes by maternal weight with the expression level of leptin receptor in maternal peripheral blood mononuclear cell (PBMC) and placental tissue.
Women with full-term gestation and its offspring were enrolled. Total RNA from maternal PBMC and placenta was obtained to perform the analysis of expression of the leptin receptor (LEPR) gene trough real-time PCR technique. Data were analyzed using one-way ANOVA or Mann-Whitney u test when applicable. Pearson correlation coefficient was used to determine the relationship between continuous variables (Stata v.13); p≤0.05 was considered statistically significant.
No statistically significant differences were found between LEPR expression level and the BMI studied groups in maternal PBMC and placental tissue. Interaction between gestational weight gain (GWG) and LEPR in maternal PBMC explain in a 32% the variability of the newborn weight.
LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight.
LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight.Lipopolysaccharide is a potent virulence factor of Porphyromonas gingivalis and has been implicated predominant pathogen in the development and progression of periodontal diseases. The aim of this study was to determine the effect of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on cementoblasts. Cementoblast (OCCM-30) were evaluated proliferation using real-time cell analyzer. In addition, total RNA was isolated at 8, 16, 24 and 72 h from 1000 ng/mL Pg-LPS treated OCCM-30 cells and mRNA expressions of pro/anti-inflammatory cytokine mediators, extracellular matrix enzymes and their tissue inhibitors and of oxidative stress enzymes were studied by real-time polymerase chain reaction. Proliferation analysis indicated that Pg-LPS slightly decreased proliferation of OCCM-30. Pg-LPS had a time-dependent impact on the expression of cytokines and enzymes. There was statistically significant up-regulation of IL-1β and IL-10 in response to Pg-LPS at 8, 16, 24, 72 h but IL-6 expression was reduced compared to control at 8 h.
Hospitalized patients with COVID-19 are at high risk for anxiety and depression, but most studies about mental health during the pandemic included the general public, healthcare workers, and students. We aimed to explore the anxiety and depression levels, prevalence and predictors in patients hospitalized with COVID-19. In this cross-sectional, exploratory study, sociodemographic and clinical features of 281 patients with confirmed COVID-19 were explored. Patients underwent a comprehensive psychiatric assessment and the Hospital Anxiety and Depression Scale (HADS) was administered through a telephonic interview. The mean age of the participants was 55.0 ± 14.9 years. One hundred forty-three (50.9%) patients were male, and 138 (49.1%) were female. Ninety-eight (34.9%) patients had significant levels of anxiety and 118 (42.0%) had significant levels of depression. Female gender, staying alone in a hospital room, early days of hospital stay, and any lifetime psychiatric disorder was associated with symptoms of anxiety. Being over 50 years of age, staying alone in a hospital room, and NSAID use before the week of hospital admission were associated with symptoms of depression. https://www.selleckchem.com/products/ide397-gsk-4362676.html Anxiety and depression levels were lower when family members who tested positive for COVID-19 stayed in the same hospital room during treatment. Women, patients >50 years, patients who used NSAIDs before hospital admission, and those with lifetime psychiatric disorders may be at risk for anxiety and depressive symptoms in the COVID-19 ward. Allowing family members with COVID-19 to stay in the same hospital room may be associated with lower anxiety and depression levels. 50 years, patients who used NSAIDs before hospital admission, and those with lifetime psychiatric disorders may be at risk for anxiety and depressive symptoms in the COVID-19 ward. Allowing family members with COVID-19 to stay in the same hospital room may be associated with lower anxiety and depression levels.For a definite indication for immunotherapy, finding appropriate biomarkers that are predictive of treatment responses is necessary. Inflammatory cytokines which play critical roles in immunity against infectious sources or cancer cells are suggested to activate immune cells after initiation of immune checkpoint inhibitors (ICI). Through activation of immune cells such as T cells, natural killer cells, macrophages, or tumor infiltrating dendritic cells, inflammatory cytokines usually increase after programmed death (PD)-1/PD-L1 axis blockade. There have been several studies evaluating the predictive value of early changes in inflammatory cytokines in non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. In this mini-review, we went through recent articles on potential blood level values of inflammatory cytokines in NSCLC patients receiving ICI and their early change around commencement of ICIs in predicting response to treatment and disease progression. The studies evaluated cytokines including interleukin (IL)-2, 6, 8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for predictability for responses to ICI. A combination cytokine panel can help predict the response and prognosis of patients with NSCLC who are receiving ICI treatment. Furthermore, a more individualized ICI treatment will be available if responses and change in tumor burden can be predicted. However, most of the studies on cytokines in NSCLC patients receiving ICIs had a small number of patients, and the heterogeneous measurement time points. Nevertheless, cytokines such as IL-8 and IFN- γ have considerable potential predictive value for immunotherapy response, which is worthy of further studies. To utilize blood cytokines levels as biomarkers for immunotherapy, a larger study with uniform measurement protocol is necessary. The pregnancy period represents the most intense period of growth and development. Pre-pregnancy weight influences weight gain during pregnancy. Leptin is a hormone mainly derived from white adipose tissue, during pregnancy leptin is also produced by the placenta. It has been suggested that the effects of placental leptin on the mother may contribute to endocrine-mediated alterations in energy balance; a dysregulation in leptin levels or its receptors may lead to poor birth outcomes. Therefore, the main goal of the present study was to analyze the differences in birth outcomes by maternal weight with the expression level of leptin receptor in maternal peripheral blood mononuclear cell (PBMC) and placental tissue. Women with full-term gestation and its offspring were enrolled. Total RNA from maternal PBMC and placenta was obtained to perform the analysis of expression of the leptin receptor (LEPR) gene trough real-time PCR technique. Data were analyzed using one-way ANOVA or Mann-Whitney u test when applicable. Pearson correlation coefficient was used to determine the relationship between continuous variables (Stata v.13); p≤0.05 was considered statistically significant. No statistically significant differences were found between LEPR expression level and the BMI studied groups in maternal PBMC and placental tissue. Interaction between gestational weight gain (GWG) and LEPR in maternal PBMC explain in a 32% the variability of the newborn weight. LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight. LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight.Lipopolysaccharide is a potent virulence factor of Porphyromonas gingivalis and has been implicated predominant pathogen in the development and progression of periodontal diseases. The aim of this study was to determine the effect of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on cementoblasts. Cementoblast (OCCM-30) were evaluated proliferation using real-time cell analyzer. In addition, total RNA was isolated at 8, 16, 24 and 72 h from 1000 ng/mL Pg-LPS treated OCCM-30 cells and mRNA expressions of pro/anti-inflammatory cytokine mediators, extracellular matrix enzymes and their tissue inhibitors and of oxidative stress enzymes were studied by real-time polymerase chain reaction. Proliferation analysis indicated that Pg-LPS slightly decreased proliferation of OCCM-30. Pg-LPS had a time-dependent impact on the expression of cytokines and enzymes. There was statistically significant up-regulation of IL-1β and IL-10 in response to Pg-LPS at 8, 16, 24, 72 h but IL-6 expression was reduced compared to control at 8 h.0 Kommentare 0 Geteilt 0 Ansichten 0 Bewertungen -
fection at 2 years of follow-up. Additionally, patients with spacer exchange demonstrated lower postoperative PROM scores and diminished improvement in multiple PROM scores after reimplantation, indicating that an interim spacer exchange in 2-stage revision is associated with worse patient outcomes.
Secondary osteonecrosis of the knee (SOK) generally occurs in relatively young patients; at advanced stages of SOK, the only viable surgical option is total knee arthroplasty (TKA). We conducted a retrospective study to investigate implant survivorship, clinical and radiographic outcomes, and complications of contemporary cemented bicompartmental TKA with/without patellar resurfacing for SOK.
Thirty-eight cemented TKAs in 27 patients with atraumatic SOK, mean age 43 years (17 to 65), were retrospectively reviewed. Seventy-four percent had a history of corticosteroid use, and 18% had a history of alcohol abuse. Patellar osteonecrosis was coincidentally found in six knees (16%), and all were asymptomatic without joint collapse. The mean followup was 7 years (2 to 12). Knee Society Score (KSS) and radiographic outcomes were evaluated at 6 weeks, 1 year, then every 2 to 3 years.
Ninety-two percent had implant survivorship free from revision with significant improvement in KSS. Causes of revision included aseptic tibial loosening (one), deep infection (one), and instability with patellofemoral issues (one). Four of six cases also with patellar osteonecrosis received resurfacing, including one with periprosthetic patellar fracture after minor trauma, with satisfactory clinical results after conservative treatment. None of the unrevised knees had progressive radiolucent lines or evidence of loosening. An unresurfaced patella, use of a stem extension or a varus-valgus constrained prosthesis constituted 18%, 8% and 3%, respectively.
Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation.
Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation.
Hispanic adolescents in the U.S. are disproportionately affected by overweight and obesity compared with their White, non-Hispanic counterparts. This study examines the efficacy of an evidence-based family intervention adapted to target obesity-related outcomes among Hispanic adolescents who were overweight/obese compared with prevention as usual.
This study was an RCT.
Participants were Hispanic adolescents who were overweight/obese (n=280, mean age=13.01 [SD=0.82] years) in the 7th/8th grade and their primary caregivers. Primary caregivers were majority female legal guardians (88% female, mean age=41.88 [SD=6.50] years).
Participants were randomized into the family-level obesity-targeted intervention or referral to community services offered for overweight/obese adolescents and families (condition). Data collection began in 2015.
Primary outcomes included dietary intake (e.g., reduction of sweetened beverages) and past-month moderate-to-vigorous physical activity. Secondary outcomes were BMI and ftion strategies (e.g., booster sessions, increased nutritional information) may be necessary to sustain beneficial effects and extend effects to adolescent participants.
This study is registered at www.clinicaltrials.gov NCT03943628.
This study is registered at www.clinicaltrials.gov NCT03943628.
Exposure to disaster-related media may be a risk factor for mental distress, but this has not been examined in the context of the COVID-19 pandemic. This study assesses whether exposure to social and traditional media during the rise of the COVID-19 pandemic was associated with mental distress among U.S. adults.
Data came from the Understanding America Study, conducted with a cross-sectional, nationally representative sample of adults who completed surveys online. Participants included 6,329 adults surveyed between March 10 and March 31, 2020. Regression analyses examined the associations of (1) self-reported average time spent on social media in a day (hours) and (2) number of traditional media sources (radio, TV, and newspaper) consulted to learn about COVID-19 with self-reported mental distress (4-item Patient Health Questionnaire). Data were analyzed in April 2020.
Participants responding at later survey dates reported more time spent on social media (β=0.02, 95% CI=0.01, 0.03), a greater number of traditional media sources consulted to learn about COVID-19 (β=0.01, 95% CI=0.01, 0.02), and greater mental distress (β=0.07, 95% CI=0.04, 0.09). Increased time spent on social media and consulting a greater number of traditional media sources to learn about COVID-19 were independently associated with increased mental distress, even after adjusting for potential confounders (social media β=0.14, 95% CI=0.05, 0.23; traditional media β=0.14, 95% CI=0.08, 0.20).
Exposure to a greater number of traditional media sources and more hours on social media was modestly associated with mental distress during the rise of the COVID-19 pandemic in the U.S.
Exposure to a greater number of traditional media sources and more hours on social media was modestly associated with mental distress during the rise of the COVID-19 pandemic in the U.S.
Severe hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic) is associated with a twofold increase in the relative risk of death. At the authors' Federally Qualified Health Center in the Southeast, 39% of adults (n=8,695) had hypertension, and 3% (n=235) were severe. The purpose of this project was to lower blood pressure and improve the proportion of patients achieving the Agency for Healthcare Research and Quality goal for blood pressure.
This quality improvement project was performed in 2017 in three 3-month Plan, Do, Study, Act cycles using a multidisciplinary outreach model in a community-based primary care setting. A clinical team including physicians, nurses, patient navigators, behavioral health counselors, and pharmacists contacted adult patients with severe hypertension (≥180/110 mmHg), scheduled visits, and established blood pressure and medication management goals. https://www.selleckchem.com/MEK.html The data review and analysis concluded in 2019.
Among patients with blood pressure ≥180/110 mmHg (n=235), the average age was 57 years (SD=12 years), 37% (n=87) were male, 82% (n=193) were Black, and 46% (n=108) were uninsured.
fection at 2 years of follow-up. Additionally, patients with spacer exchange demonstrated lower postoperative PROM scores and diminished improvement in multiple PROM scores after reimplantation, indicating that an interim spacer exchange in 2-stage revision is associated with worse patient outcomes. Secondary osteonecrosis of the knee (SOK) generally occurs in relatively young patients; at advanced stages of SOK, the only viable surgical option is total knee arthroplasty (TKA). We conducted a retrospective study to investigate implant survivorship, clinical and radiographic outcomes, and complications of contemporary cemented bicompartmental TKA with/without patellar resurfacing for SOK. Thirty-eight cemented TKAs in 27 patients with atraumatic SOK, mean age 43 years (17 to 65), were retrospectively reviewed. Seventy-four percent had a history of corticosteroid use, and 18% had a history of alcohol abuse. Patellar osteonecrosis was coincidentally found in six knees (16%), and all were asymptomatic without joint collapse. The mean followup was 7 years (2 to 12). Knee Society Score (KSS) and radiographic outcomes were evaluated at 6 weeks, 1 year, then every 2 to 3 years. Ninety-two percent had implant survivorship free from revision with significant improvement in KSS. Causes of revision included aseptic tibial loosening (one), deep infection (one), and instability with patellofemoral issues (one). Four of six cases also with patellar osteonecrosis received resurfacing, including one with periprosthetic patellar fracture after minor trauma, with satisfactory clinical results after conservative treatment. None of the unrevised knees had progressive radiolucent lines or evidence of loosening. An unresurfaced patella, use of a stem extension or a varus-valgus constrained prosthesis constituted 18%, 8% and 3%, respectively. Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation. Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation. Hispanic adolescents in the U.S. are disproportionately affected by overweight and obesity compared with their White, non-Hispanic counterparts. This study examines the efficacy of an evidence-based family intervention adapted to target obesity-related outcomes among Hispanic adolescents who were overweight/obese compared with prevention as usual. This study was an RCT. Participants were Hispanic adolescents who were overweight/obese (n=280, mean age=13.01 [SD=0.82] years) in the 7th/8th grade and their primary caregivers. Primary caregivers were majority female legal guardians (88% female, mean age=41.88 [SD=6.50] years). Participants were randomized into the family-level obesity-targeted intervention or referral to community services offered for overweight/obese adolescents and families (condition). Data collection began in 2015. Primary outcomes included dietary intake (e.g., reduction of sweetened beverages) and past-month moderate-to-vigorous physical activity. Secondary outcomes were BMI and ftion strategies (e.g., booster sessions, increased nutritional information) may be necessary to sustain beneficial effects and extend effects to adolescent participants. This study is registered at www.clinicaltrials.gov NCT03943628. This study is registered at www.clinicaltrials.gov NCT03943628. Exposure to disaster-related media may be a risk factor for mental distress, but this has not been examined in the context of the COVID-19 pandemic. This study assesses whether exposure to social and traditional media during the rise of the COVID-19 pandemic was associated with mental distress among U.S. adults. Data came from the Understanding America Study, conducted with a cross-sectional, nationally representative sample of adults who completed surveys online. Participants included 6,329 adults surveyed between March 10 and March 31, 2020. Regression analyses examined the associations of (1) self-reported average time spent on social media in a day (hours) and (2) number of traditional media sources (radio, TV, and newspaper) consulted to learn about COVID-19 with self-reported mental distress (4-item Patient Health Questionnaire). Data were analyzed in April 2020. Participants responding at later survey dates reported more time spent on social media (β=0.02, 95% CI=0.01, 0.03), a greater number of traditional media sources consulted to learn about COVID-19 (β=0.01, 95% CI=0.01, 0.02), and greater mental distress (β=0.07, 95% CI=0.04, 0.09). Increased time spent on social media and consulting a greater number of traditional media sources to learn about COVID-19 were independently associated with increased mental distress, even after adjusting for potential confounders (social media β=0.14, 95% CI=0.05, 0.23; traditional media β=0.14, 95% CI=0.08, 0.20). Exposure to a greater number of traditional media sources and more hours on social media was modestly associated with mental distress during the rise of the COVID-19 pandemic in the U.S. Exposure to a greater number of traditional media sources and more hours on social media was modestly associated with mental distress during the rise of the COVID-19 pandemic in the U.S. Severe hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic) is associated with a twofold increase in the relative risk of death. At the authors' Federally Qualified Health Center in the Southeast, 39% of adults (n=8,695) had hypertension, and 3% (n=235) were severe. The purpose of this project was to lower blood pressure and improve the proportion of patients achieving the Agency for Healthcare Research and Quality goal for blood pressure. This quality improvement project was performed in 2017 in three 3-month Plan, Do, Study, Act cycles using a multidisciplinary outreach model in a community-based primary care setting. A clinical team including physicians, nurses, patient navigators, behavioral health counselors, and pharmacists contacted adult patients with severe hypertension (≥180/110 mmHg), scheduled visits, and established blood pressure and medication management goals. https://www.selleckchem.com/MEK.html The data review and analysis concluded in 2019. Among patients with blood pressure ≥180/110 mmHg (n=235), the average age was 57 years (SD=12 years), 37% (n=87) were male, 82% (n=193) were Black, and 46% (n=108) were uninsured.0 Kommentare 0 Geteilt 0 Ansichten 0 Bewertungen -
Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Low-density lipoprotein receptor (LDLR) plays a critical role in plasma lipoprotein hemostasis, which is involved in the formation of atherosclerotic plaque. This study aimed to evaluate whether LDLR gene polymorphisms are significantly associated with ACS and the plasma lipids profile. Three LDLR gene polymorphisms located in the UTR'3 region (c.*52 A/G, c.*504 A/G, and c.* 773 A/G) were determined using TaqMan genotyping assays in a group of 618 ACS patients and 666 healthy controls. Plasma lipids profile concentrations were determined by enzymatic/colorimetric assays. Under co-dominant and recessive models, the c.*52 A allele of the c.*52 A/G polymorphism was associated with a higher risk of ACS (OR = 2.02, pCCo-dom = 0.033, and OR = 2.00, pCRes = 0.009, respectively). In the same way, under co-dominant and recessive models, the c.*773 G allele of the c.*773 A/G polymorphism was associated with a high risk of ACS (OR = 2.04, pCCo-dom = 0.027, and OR = 2.01, pCRes = 0.007, respectively). The "AAG" haplotype was associated with a high risk of ACS (OR = 1.22, pC = 0.016). The c.*52 AA genotype showed a lower HDL-C concentration than individuals with the GG genotype. In addition, carriers of c.*773 GG genotype carriers had a lower concentration of the high-density lipoprotein-cholesterol (HDL-C) than subjects with the AA genotype. Our data suggest the association of the LDLRc.*773 A/G and LDLR c.*52 A/G polymorphisms with both the risk of developing ACS and with a lower concentration of HDL-C in the study population.Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20-65 year-olds to 4.5 in the >80 year-olds (p less then 0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care.Current research to find effective anticancer treatments is being performed on photodynamic therapy (PDT) with increasing attention. https://www.selleckchem.com/products/chroman-1.html PDT is a very promising therapeutic way to combine a photosensitive drug with visible light to manage different intense malignancies. PDT has several benefits, including better safety and lower toxicity in the treatment of malignant tumors over traditional cancer therapy. This reasonably simple approach utilizes three integral elements a photosensitizer (PS), a source of light, and oxygen. Upon light irradiation of a particular wavelength, the PS generates reactive oxygen species (ROS), beginning a cascade of cellular death transformations. The positive therapeutic impact of PDT may be limited because several factors of this therapy include low solubilities of PSs, restricting their effective administration, blood circulation, and poor tumor specificity. Therefore, utilizing nanocarrier systems that modulate PS pharmacokinetics (PK) and pharmacodynamics (PD) is a promising approach to bypassing these challenges. In the present paper, we review the latest clinical studies and preclinical in vivo studies on the use of PDT and progress made in the use of nanotherapeutics as delivery tools for PSs to improve their cancer cellular uptake and their toxic properties and, therefore, the therapeutic impact of PDT. We also discuss the effects that photoimmunotherapy (PIT) might have on solid tumor therapeutic strategies.Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury.
Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Low-density lipoprotein receptor (LDLR) plays a critical role in plasma lipoprotein hemostasis, which is involved in the formation of atherosclerotic plaque. This study aimed to evaluate whether LDLR gene polymorphisms are significantly associated with ACS and the plasma lipids profile. Three LDLR gene polymorphisms located in the UTR'3 region (c.*52 A/G, c.*504 A/G, and c.* 773 A/G) were determined using TaqMan genotyping assays in a group of 618 ACS patients and 666 healthy controls. Plasma lipids profile concentrations were determined by enzymatic/colorimetric assays. Under co-dominant and recessive models, the c.*52 A allele of the c.*52 A/G polymorphism was associated with a higher risk of ACS (OR = 2.02, pCCo-dom = 0.033, and OR = 2.00, pCRes = 0.009, respectively). In the same way, under co-dominant and recessive models, the c.*773 G allele of the c.*773 A/G polymorphism was associated with a high risk of ACS (OR = 2.04, pCCo-dom = 0.027, and OR = 2.01, pCRes = 0.007, respectively). The "AAG" haplotype was associated with a high risk of ACS (OR = 1.22, pC = 0.016). The c.*52 AA genotype showed a lower HDL-C concentration than individuals with the GG genotype. In addition, carriers of c.*773 GG genotype carriers had a lower concentration of the high-density lipoprotein-cholesterol (HDL-C) than subjects with the AA genotype. Our data suggest the association of the LDLRc.*773 A/G and LDLR c.*52 A/G polymorphisms with both the risk of developing ACS and with a lower concentration of HDL-C in the study population.Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20-65 year-olds to 4.5 in the >80 year-olds (p less then 0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care.Current research to find effective anticancer treatments is being performed on photodynamic therapy (PDT) with increasing attention. https://www.selleckchem.com/products/chroman-1.html PDT is a very promising therapeutic way to combine a photosensitive drug with visible light to manage different intense malignancies. PDT has several benefits, including better safety and lower toxicity in the treatment of malignant tumors over traditional cancer therapy. This reasonably simple approach utilizes three integral elements a photosensitizer (PS), a source of light, and oxygen. Upon light irradiation of a particular wavelength, the PS generates reactive oxygen species (ROS), beginning a cascade of cellular death transformations. The positive therapeutic impact of PDT may be limited because several factors of this therapy include low solubilities of PSs, restricting their effective administration, blood circulation, and poor tumor specificity. Therefore, utilizing nanocarrier systems that modulate PS pharmacokinetics (PK) and pharmacodynamics (PD) is a promising approach to bypassing these challenges. In the present paper, we review the latest clinical studies and preclinical in vivo studies on the use of PDT and progress made in the use of nanotherapeutics as delivery tools for PSs to improve their cancer cellular uptake and their toxic properties and, therefore, the therapeutic impact of PDT. We also discuss the effects that photoimmunotherapy (PIT) might have on solid tumor therapeutic strategies.Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury.0 Kommentare 0 Geteilt 0 Ansichten 0 Bewertungen -
A rational design of electrode materials with both high electron conductivity and abundant of catalytic sites is essential for high-performance electrochemical reactions. Herein, a nitrogen and sulfur co-doped graphene (SNG) anchored on the interconnected conductive graphite foam (GF) is fabricated via drop-casting and in situ annealing. The SNG flakes are tightly immobilized on the GF surface, which can provide fast electron transfer rate and large electrolyte/electrode interfaces. The SNG@GF composite can be directly used as a free-standing electrode for electro-catalytic degradation of organic pollutants and overall water splitting. SNG@GF significantly enhanced the electrochemical activation of peroxymonosulfate (PMS) for catalytic oxidation. During the oxygen evolution reaction (OER), the SNG@GF exhibits an initial overpotential of 330 mV vs. RHE at 10 mA cm-2 with a Tafel slope of 149 mV dec-1 in 1 M KOH, which outperforms most of the reported metal-free catalysts. The density functional theory calculations are also used to unveil the S, N dual doping effects of carbon materials and their synergy in carbocatalysis. This study dedicates to developing multi-functional carbocatalysts for environmental and energy applications, and enables insights into carbocatalysis in electrochemistry.Collaborative care in primary care has been shown to be effective for subthreshold depression in older adults in the 'CASPER' trial. However, to understand the impact of adherence, and to explore the minimum effective dose of collaborative care, we reanalysed the trial data using a complier average causal effect (CACE) analysis. Data were available for 705 participants, 519 with 12-month PHQ-9 scores. 'Compliance' could be observed for participants in the intervention group. Latent complier status in the control group was estimated. Completion of five or more sessions of care was defined as 'compliance'. Sensitivity analyses, using alternative cut-offs of two to eight sessions, assessed the impact of changing the definition of 'compliance'. Compliers in the intervention group had lower PHQ-9 scores at 12-month follow up than assumed compliers in the control group (1.75 lower, 95% confidence interval 0.29 to 3.21, p = 0.02), a greater effect than originally reported. Sensitivity analyses confirmed statistically significant differences between the intervention and control groups in those attending five or more sessions. We conclude that collaborative care is causally effective in reducing subthreshold depressive symptoms in older people who adhere to treatment. Our findings suggest the minimum effective dose is five sessions.
Around half of people diagnosed with schizophrenia suffer from co-morbid depression, yet there are no evidence-based psychological treatments to target this presentation.
Participants were aged 18-65 years old, had a clinical diagnosis of schizophrenia or schizoaffective disorder and at least a mild level of depression. Participants were randomly assigned (11) to receive PoMeT or treatment as usual. https://www.selleckchem.com/pharmacological_epigenetics.html PoMeT was delivered in up to 12 individual sessions within 3 months. We stratified randomisation by site and by severity of depression using randomised-permuted blocks. Assessments were carried out at baseline, 3-month, 6-month and 9-month by assessors who were blind to treatment allocation. The primary outcome was reduction in the symptoms of depression at 3-month, 6-month and 9-month as measured by the BDI-II. Analysis was by intention-to-treat with linear mixed-effects models. The trial was registered with the ISRCTN registry number 99485756.
One hundred participants were randomly assigned to either PoMeT.Hepatic in vitro biotransformation assays, in combination with in vitro-in vivo extrapolation (IVIVE) and bioaccumulation modeling, can be used to support regulatory bioaccumulation assessments. In most applications, however, these methods ignore the possibility of extrahepatic metabolism. Here we evaluated intestinal biotransformation in rainbow trout using S9 fractions prepared from the upper intestinal (***) epithelium. Measured levels of activity determined using standard substrates for phase I and phase II biotransformation enzymes were within 2-fold of activities measured in hepatic S9 fractions. In vitro intrinsic clearance rates for 2-ethylhexyl-4-methoxycinnamate (EHMC; an organic sunscreen agent) and two polycyclic aromatic hydrocarbons (pyrene [PYR] and benzo(a)pyrene [BAP]) were significantly higher in liver S9 fractions than in *** S9 fractions. For octocrylene (OCT; a second sunscreen agent), however, in vitro intrinsic clearance rates were higher in *** S9 fractions compared to liver S9 fractions. An existing 'liver only' IVIVE model was expanded to consider biotransformation in both the liver and ***. Relevant IVIVE scaling factors were developed by morphological, histological, and biochemical evaluation of trout intestines. For chemicals biotransformed at higher rates by hepatic S9 fractions (i.e., BAP, PYR, EHMC), the 'liver & ***' model yielded whole-body biotransformation rate constants (kMET) that were within 1.2 to 1.4-fold of those estimated using the 'liver only' model. In contrast to these findings, the mean kMET for OCT obtained using the 'liver & ***' model was 3.3 times higher than the mean kMET derived using the 'liver only' model and was in good agreement with empirical kMET estimates determined previously for trout ( less then 20 % difference). The results of this study suggest that current 'liver only' IVIVE approaches may underestimate in vivo biotransformation rates for chemicals that undergo substantial biotransformation in the ***.We describe the total synthesis of tutuilamide A, a potent porcine pancreatic elastase (PPE) inhibitor and a representative member of the 3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide family, isolated from marine cyanobacteria. The Ahp unit serves as a pharmacophore and the adjacent 2-amino-2-butenoic acid (Abu) is a main driver of the selectivity among serine proteases. We adapted our previous convergent strategy to generate the macrocycle, common with lyngbyastatin 7 and related elastase inhibitors, and then appended the tutuilamide A-specific side chain bearing a vinyl chloride. Tutuilamide A and lyngbyastatin 7 were evaluated side by side for the inhibition of the disease-relevant human neutrophil elastase (HNE). Tutuilamide A and lyngbyastatin 7 were approximately equipotent against HNE, while tutuilamide A was previously shown to be more active against PPE compared with lyngbyastatin 7, further demonstrating that the side chain provides opportunities to not only modulate potency but also selectivity among proteases of the same function from different organisms.
A rational design of electrode materials with both high electron conductivity and abundant of catalytic sites is essential for high-performance electrochemical reactions. Herein, a nitrogen and sulfur co-doped graphene (SNG) anchored on the interconnected conductive graphite foam (GF) is fabricated via drop-casting and in situ annealing. The SNG flakes are tightly immobilized on the GF surface, which can provide fast electron transfer rate and large electrolyte/electrode interfaces. The SNG@GF composite can be directly used as a free-standing electrode for electro-catalytic degradation of organic pollutants and overall water splitting. SNG@GF significantly enhanced the electrochemical activation of peroxymonosulfate (PMS) for catalytic oxidation. During the oxygen evolution reaction (OER), the SNG@GF exhibits an initial overpotential of 330 mV vs. RHE at 10 mA cm-2 with a Tafel slope of 149 mV dec-1 in 1 M KOH, which outperforms most of the reported metal-free catalysts. The density functional theory calculations are also used to unveil the S, N dual doping effects of carbon materials and their synergy in carbocatalysis. This study dedicates to developing multi-functional carbocatalysts for environmental and energy applications, and enables insights into carbocatalysis in electrochemistry.Collaborative care in primary care has been shown to be effective for subthreshold depression in older adults in the 'CASPER' trial. However, to understand the impact of adherence, and to explore the minimum effective dose of collaborative care, we reanalysed the trial data using a complier average causal effect (CACE) analysis. Data were available for 705 participants, 519 with 12-month PHQ-9 scores. 'Compliance' could be observed for participants in the intervention group. Latent complier status in the control group was estimated. Completion of five or more sessions of care was defined as 'compliance'. Sensitivity analyses, using alternative cut-offs of two to eight sessions, assessed the impact of changing the definition of 'compliance'. Compliers in the intervention group had lower PHQ-9 scores at 12-month follow up than assumed compliers in the control group (1.75 lower, 95% confidence interval 0.29 to 3.21, p = 0.02), a greater effect than originally reported. Sensitivity analyses confirmed statistically significant differences between the intervention and control groups in those attending five or more sessions. We conclude that collaborative care is causally effective in reducing subthreshold depressive symptoms in older people who adhere to treatment. Our findings suggest the minimum effective dose is five sessions. Around half of people diagnosed with schizophrenia suffer from co-morbid depression, yet there are no evidence-based psychological treatments to target this presentation. Participants were aged 18-65 years old, had a clinical diagnosis of schizophrenia or schizoaffective disorder and at least a mild level of depression. Participants were randomly assigned (11) to receive PoMeT or treatment as usual. https://www.selleckchem.com/pharmacological_epigenetics.html PoMeT was delivered in up to 12 individual sessions within 3 months. We stratified randomisation by site and by severity of depression using randomised-permuted blocks. Assessments were carried out at baseline, 3-month, 6-month and 9-month by assessors who were blind to treatment allocation. The primary outcome was reduction in the symptoms of depression at 3-month, 6-month and 9-month as measured by the BDI-II. Analysis was by intention-to-treat with linear mixed-effects models. The trial was registered with the ISRCTN registry number 99485756. One hundred participants were randomly assigned to either PoMeT.Hepatic in vitro biotransformation assays, in combination with in vitro-in vivo extrapolation (IVIVE) and bioaccumulation modeling, can be used to support regulatory bioaccumulation assessments. In most applications, however, these methods ignore the possibility of extrahepatic metabolism. Here we evaluated intestinal biotransformation in rainbow trout using S9 fractions prepared from the upper intestinal (GIT) epithelium. Measured levels of activity determined using standard substrates for phase I and phase II biotransformation enzymes were within 2-fold of activities measured in hepatic S9 fractions. In vitro intrinsic clearance rates for 2-ethylhexyl-4-methoxycinnamate (EHMC; an organic sunscreen agent) and two polycyclic aromatic hydrocarbons (pyrene [PYR] and benzo(a)pyrene [BAP]) were significantly higher in liver S9 fractions than in GIT S9 fractions. For octocrylene (OCT; a second sunscreen agent), however, in vitro intrinsic clearance rates were higher in GIT S9 fractions compared to liver S9 fractions. An existing 'liver only' IVIVE model was expanded to consider biotransformation in both the liver and GIT. Relevant IVIVE scaling factors were developed by morphological, histological, and biochemical evaluation of trout intestines. For chemicals biotransformed at higher rates by hepatic S9 fractions (i.e., BAP, PYR, EHMC), the 'liver & GIT' model yielded whole-body biotransformation rate constants (kMET) that were within 1.2 to 1.4-fold of those estimated using the 'liver only' model. In contrast to these findings, the mean kMET for OCT obtained using the 'liver & GIT' model was 3.3 times higher than the mean kMET derived using the 'liver only' model and was in good agreement with empirical kMET estimates determined previously for trout ( less then 20 % difference). The results of this study suggest that current 'liver only' IVIVE approaches may underestimate in vivo biotransformation rates for chemicals that undergo substantial biotransformation in the GIT.We describe the total synthesis of tutuilamide A, a potent porcine pancreatic elastase (PPE) inhibitor and a representative member of the 3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide family, isolated from marine cyanobacteria. The Ahp unit serves as a pharmacophore and the adjacent 2-amino-2-butenoic acid (Abu) is a main driver of the selectivity among serine proteases. We adapted our previous convergent strategy to generate the macrocycle, common with lyngbyastatin 7 and related elastase inhibitors, and then appended the tutuilamide A-specific side chain bearing a vinyl chloride. Tutuilamide A and lyngbyastatin 7 were evaluated side by side for the inhibition of the disease-relevant human neutrophil elastase (HNE). Tutuilamide A and lyngbyastatin 7 were approximately equipotent against HNE, while tutuilamide A was previously shown to be more active against PPE compared with lyngbyastatin 7, further demonstrating that the side chain provides opportunities to not only modulate potency but also selectivity among proteases of the same function from different organisms.0 Kommentare 0 Geteilt 0 Ansichten 0 Bewertungen -
Interestingly, carbohydrate-induced insulin signaling appears to activate FAK at the level of IRS-1 but did not enhance mTOR activity 1 h post-exercise greater than the placebo condition. Future research should investigate these interactions under different conditions and within different time frames to clearly understand the interactions between these signaling molecules.Persistent infection of chicken anemia virus (CAV) in chickens has been suspected to result in immunosuppression and exogenous virus contamination within vaccine production. However, no direct evidence for persistent CAV infection has thus far been obtained. In this study, we aimed to establish an in vitro model of persistent CAV infection. CAV-infected ****-MSB1 (MSB1) cells, a Marek's disease virus-transformed continuous cell line, were cultured in the presence of both CAV and CAV neutralizing antibody (NA). Cell viability, expression of viral antigens, viral DNA, and recovery of CAV were examined by acridine orange/propidium iodide staining, immunofluorescence measurement, real-time PCR, and viral isolation, respectively. The results indicated that CAV was maintained and possibly replicated in CAV-infected cells cultured in the presence of NA, without affecting host cell viability. It was also shown that persistently infectious CAV induced cell death again after removing NA. The persistent infection of CAV in MSB1 cells was not related to viral gene mutation. In summary, we have herein established a novel model of persistent CAV infection in MSB1 cells cultured in the presence of NA.Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male **** were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In contrast, the HF and HS diets caused lipid peroxidation and provoked altered antioxidant enzyme levels/activities in liver tissue. Our work provides evidence that hepatic oxidative damage may be caused by augmented levels of peroxisomes and consequently higher peroxisomal FAO-induced ROS in the early NAFLD stage. Hepatic damage is also associated with autophagic flux impairment, which was demonstrated to be diet-type dependent. The HS diet induced a reduction in autophagosomal formation, while the HF diet reduced levels of cathepsins. The accumulation of damaged organelles could instigate hepatocyte injuries and NAFLD progression.In recent years, the interest in the sorption properties of coal in conditions corresponding to in situ has increased due to the continuous development of research on CO2-ECBM (Enhanced Coal Bed Methane recovery) technology. In order to gain a better insight into a number of phenomena related to filtration, sorption and CO2/CH4 exchange sorption occurring in coal loaded with confining pressure, which corresponds to the in situ conditions, an innovative research apparatus was built to enable temporal and spatial analysis of these phenomena. The constructed apparatus consists of three systems a high-pressure system, a gas injection system and a gas emission system. The work presents the results of basic apparatus tests, which were aimed at checking its correct operation and determining its specifications. These tests involved carrying out trial measurements of methane (CH4) filtration processes, CH4 sorption and CO2/CH4 exchange sorption on a coal sample. The results of the tests showed among other things that the apparatus ensured the regulation of the confining pressure in the range of 0.1-40 MPa, the regulation of the pressure at the inlet and outlet of the sample in the range of 0.1-1.6 MPa and 0.1-1.0 MPa and the measurement of changes in the sample volume in the range of 0-7.85 cm3. The results of the tests confirmed the correct functioning of the constructed apparatus.Various indoor positioning methods have been developed to solve the "last mile on Earth". Ultra-wideband positioning technology stands out among all indoor positioning methods due to its unique communication mechanism and has a broad application prospect. https://www.selleckchem.com/products/cx-5461.html Under non-line-of-sight (NLOS) conditions, the accuracy of this positioning method is greatly affected. Unlike traditional inspection and rejection of NLOS signals, all base stations are involved in positioning to improve positioning accuracy. In this paper, a Long Short-Term Memory (LSTM) network is used while maximizing the use of positioning equipment. The LSTM network is applied to process the raw Channel Impulse Response (CIR) to calculate the ranging error, and combined with the improved positioning algorithm to improve the positioning accuracy. It has been verified that the accuracy of the predicted ranging error is up to centimeter level. Using this prediction for the positioning algorithm, the average positioning accuracy improved by about 62%.Convolutional neural networks (CNNs) can automatically learn features from pressure information, and some studies have applied CNNs for tactile shape recognition. However, the limited density of the sensor and its flexibility requirement lead the obtained tactile images to have a low-resolution and blurred. To address this issue, we propose a bilinear feature and multi-layer fused convolutional neural network (BMF-CNN). The bilinear calculation of the feature improves the feature extraction capability of the network. Meanwhile, the multi-layer fusion strategy exploits the complementarity of different layers to enhance the feature utilization efficiency. To validate the proposed method, a 26 class letter-shape tactile image dataset with complex edges was constructed. The BMF-CNN model achieved a 98.64% average accuracy of tactile shape. The results show that BMF-CNN can deal with tactile shapes more effectively than traditional CNN and artificial feature methods.
Interestingly, carbohydrate-induced insulin signaling appears to activate FAK at the level of IRS-1 but did not enhance mTOR activity 1 h post-exercise greater than the placebo condition. Future research should investigate these interactions under different conditions and within different time frames to clearly understand the interactions between these signaling molecules.Persistent infection of chicken anemia virus (CAV) in chickens has been suspected to result in immunosuppression and exogenous virus contamination within vaccine production. However, no direct evidence for persistent CAV infection has thus far been obtained. In this study, we aimed to establish an in vitro model of persistent CAV infection. CAV-infected MDCC-MSB1 (MSB1) cells, a Marek's disease virus-transformed continuous cell line, were cultured in the presence of both CAV and CAV neutralizing antibody (NA). Cell viability, expression of viral antigens, viral DNA, and recovery of CAV were examined by acridine orange/propidium iodide staining, immunofluorescence measurement, real-time PCR, and viral isolation, respectively. The results indicated that CAV was maintained and possibly replicated in CAV-infected cells cultured in the presence of NA, without affecting host cell viability. It was also shown that persistently infectious CAV induced cell death again after removing NA. The persistent infection of CAV in MSB1 cells was not related to viral gene mutation. In summary, we have herein established a novel model of persistent CAV infection in MSB1 cells cultured in the presence of NA.Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male mice were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In contrast, the HF and HS diets caused lipid peroxidation and provoked altered antioxidant enzyme levels/activities in liver tissue. Our work provides evidence that hepatic oxidative damage may be caused by augmented levels of peroxisomes and consequently higher peroxisomal FAO-induced ROS in the early NAFLD stage. Hepatic damage is also associated with autophagic flux impairment, which was demonstrated to be diet-type dependent. The HS diet induced a reduction in autophagosomal formation, while the HF diet reduced levels of cathepsins. The accumulation of damaged organelles could instigate hepatocyte injuries and NAFLD progression.In recent years, the interest in the sorption properties of coal in conditions corresponding to in situ has increased due to the continuous development of research on CO2-ECBM (Enhanced Coal Bed Methane recovery) technology. In order to gain a better insight into a number of phenomena related to filtration, sorption and CO2/CH4 exchange sorption occurring in coal loaded with confining pressure, which corresponds to the in situ conditions, an innovative research apparatus was built to enable temporal and spatial analysis of these phenomena. The constructed apparatus consists of three systems a high-pressure system, a gas injection system and a gas emission system. The work presents the results of basic apparatus tests, which were aimed at checking its correct operation and determining its specifications. These tests involved carrying out trial measurements of methane (CH4) filtration processes, CH4 sorption and CO2/CH4 exchange sorption on a coal sample. The results of the tests showed among other things that the apparatus ensured the regulation of the confining pressure in the range of 0.1-40 MPa, the regulation of the pressure at the inlet and outlet of the sample in the range of 0.1-1.6 MPa and 0.1-1.0 MPa and the measurement of changes in the sample volume in the range of 0-7.85 cm3. The results of the tests confirmed the correct functioning of the constructed apparatus.Various indoor positioning methods have been developed to solve the "last mile on Earth". Ultra-wideband positioning technology stands out among all indoor positioning methods due to its unique communication mechanism and has a broad application prospect. https://www.selleckchem.com/products/cx-5461.html Under non-line-of-sight (NLOS) conditions, the accuracy of this positioning method is greatly affected. Unlike traditional inspection and rejection of NLOS signals, all base stations are involved in positioning to improve positioning accuracy. In this paper, a Long Short-Term Memory (LSTM) network is used while maximizing the use of positioning equipment. The LSTM network is applied to process the raw Channel Impulse Response (CIR) to calculate the ranging error, and combined with the improved positioning algorithm to improve the positioning accuracy. It has been verified that the accuracy of the predicted ranging error is up to centimeter level. Using this prediction for the positioning algorithm, the average positioning accuracy improved by about 62%.Convolutional neural networks (CNNs) can automatically learn features from pressure information, and some studies have applied CNNs for tactile shape recognition. However, the limited density of the sensor and its flexibility requirement lead the obtained tactile images to have a low-resolution and blurred. To address this issue, we propose a bilinear feature and multi-layer fused convolutional neural network (BMF-CNN). The bilinear calculation of the feature improves the feature extraction capability of the network. Meanwhile, the multi-layer fusion strategy exploits the complementarity of different layers to enhance the feature utilization efficiency. To validate the proposed method, a 26 class letter-shape tactile image dataset with complex edges was constructed. The BMF-CNN model achieved a 98.64% average accuracy of tactile shape. The results show that BMF-CNN can deal with tactile shapes more effectively than traditional CNN and artificial feature methods.0 Kommentare 0 Geteilt 2 Ansichten 0 Bewertungen -
Eventally, the patient demonstrated nearly full recovery (modified Rankin Scale score 1). Thus, mechanical thrombectomy should be considered as a reasonable option in cases of acute cerebral stroke caused by subocclusive thrombus and progressive neurological deficits despite standard conservative therapy. J. Med. Invest. 67 372-374, August, 2020.Mammary hamartoma is benign lesion and relatively rare. 17 cases of breast cancer associated with a hamartoma had been previously documented in the literature. We describe herein a case of noninvasive ductal carcinoma of the breast arising in hamartoma in a woman of 60's. The discordance of images of the mass between mammogram and ultrasonogram can lead us to detect the carcinoma within the hamartoma in our case. J. Med. Invest. 67 368-371, August, 2020.Spindle cell carcinoma (SpCC) of the breast is quite a rare modality classified to the metaplastic carcinoma of the breast. Regarding its biological behavior and the prognosis of the patients with this rare tumor, it has been remaining controversial. We herein report an 88 year-old woman who had a huge bleeding tumor on the right breast. She was a high-aged woman with low activities of daily life, even with some suspicion of distant organ metastasis. While the tumor proved to drastically bleed due to the tumor disintegration, a right simple mastectomy was performed. According to the histopathologic examinations, sarcomatoid spindle cells with severe atypia were observed. By an immunohistochemical examination, the tumor had proved to express neither estrogen receptor, progesterone receptor nor HER2 receptor. Moreover an immunohistochemical expression of AE1/3 and CAM5.2, defining an epithelial neoplasm were observed in addition to an expression of vimentin. From these findings, this bleeding tumor was diagnosed as spindle cell carcinoma of the breast. J. Med. Invest. 67 365-367, August, 2020.The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. https://www.selleckchem.com/products/chroman-1.html A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 362-364, August, 2020.Background Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients. J. Med. Invest. 67 358-361, August, 2020.Generalized anxiety disorder (GAD) sometimes exists in the background of social withdrawal and school refusal. Although clinical evidence suggests that selective serotonin reuptake inhibitors (SSRIs) are an effective treatment for GAD, they are not officially approved for GAD in Japan. In addition, it has been established that the use of SSRIs increases the risk for suicide and activation syndrome among young individuals. As such, there is currently little domestic clinical experience in prescribing SSRIs to young patients with GAD. The authors report two cases involving 10-year-old patients with GAD who were treated successfully with escitalopram and experienced subsequent improvement in social withdrawal and school refusal. One patient had autistic spectrum disorder and exhibited self-harm associated with anxiety symptoms, requiring careful use of SSRIs under hospitalization. The other patient was treated at an outpatient clinic without any side effects. In each case, improvement of anxiety symptoms with the use of SSRIs facilitated the introduction of psychoeducation and psychotherapy. It is important to accurately diagnose GAD, which may exist in the background of patients exhibiting social withdrawal and school refusal, and to treat the disorder appropriately. J. Med. Invest. 67 355-357, August, 2020.Objective Infectious spondylodiscitis (IS) is rarely seen in healthy elementary school age children. Conservative treatment with antibiotics is usually preferable but sometimes fails because of the low identification rate of the pathogen by percutaneous needle biopsy. When surgical treatment is indicated, selecting the appropriate procedure is crucial in terms of invasiveness for such young children. Case report We present the case of a 9-year-old otherwise healthy girl with IS who successfully underwent debridement and identification of the causative pathogen using full endoscopic discectomy (FED) system. Methicillin-susceptible Staphylococcus aureus was identified on several cultures of samples. Immediately after the surgery, the LBP was significantly decreased and the remittent fever resolved dramatically. At the 1-year follow-up, she had no symptoms and plain radiographs showed bony fusion. Conclusion This is the first report on IS in elementary school-age children treated with the FED system. Debridement using this system could provide minimally invasive and effective curettage of the infected disc space and can be helpful in identifying the pathogen even for small children.
Eventally, the patient demonstrated nearly full recovery (modified Rankin Scale score 1). Thus, mechanical thrombectomy should be considered as a reasonable option in cases of acute cerebral stroke caused by subocclusive thrombus and progressive neurological deficits despite standard conservative therapy. J. Med. Invest. 67 372-374, August, 2020.Mammary hamartoma is benign lesion and relatively rare. 17 cases of breast cancer associated with a hamartoma had been previously documented in the literature. We describe herein a case of noninvasive ductal carcinoma of the breast arising in hamartoma in a woman of 60's. The discordance of images of the mass between mammogram and ultrasonogram can lead us to detect the carcinoma within the hamartoma in our case. J. Med. Invest. 67 368-371, August, 2020.Spindle cell carcinoma (SpCC) of the breast is quite a rare modality classified to the metaplastic carcinoma of the breast. Regarding its biological behavior and the prognosis of the patients with this rare tumor, it has been remaining controversial. We herein report an 88 year-old woman who had a huge bleeding tumor on the right breast. She was a high-aged woman with low activities of daily life, even with some suspicion of distant organ metastasis. While the tumor proved to drastically bleed due to the tumor disintegration, a right simple mastectomy was performed. According to the histopathologic examinations, sarcomatoid spindle cells with severe atypia were observed. By an immunohistochemical examination, the tumor had proved to express neither estrogen receptor, progesterone receptor nor HER2 receptor. Moreover an immunohistochemical expression of AE1/3 and CAM5.2, defining an epithelial neoplasm were observed in addition to an expression of vimentin. From these findings, this bleeding tumor was diagnosed as spindle cell carcinoma of the breast. J. Med. Invest. 67 365-367, August, 2020.The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. https://www.selleckchem.com/products/chroman-1.html A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 362-364, August, 2020.Background Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients. J. Med. Invest. 67 358-361, August, 2020.Generalized anxiety disorder (GAD) sometimes exists in the background of social withdrawal and school refusal. Although clinical evidence suggests that selective serotonin reuptake inhibitors (SSRIs) are an effective treatment for GAD, they are not officially approved for GAD in Japan. In addition, it has been established that the use of SSRIs increases the risk for suicide and activation syndrome among young individuals. As such, there is currently little domestic clinical experience in prescribing SSRIs to young patients with GAD. The authors report two cases involving 10-year-old patients with GAD who were treated successfully with escitalopram and experienced subsequent improvement in social withdrawal and school refusal. One patient had autistic spectrum disorder and exhibited self-harm associated with anxiety symptoms, requiring careful use of SSRIs under hospitalization. The other patient was treated at an outpatient clinic without any side effects. In each case, improvement of anxiety symptoms with the use of SSRIs facilitated the introduction of psychoeducation and psychotherapy. It is important to accurately diagnose GAD, which may exist in the background of patients exhibiting social withdrawal and school refusal, and to treat the disorder appropriately. J. Med. Invest. 67 355-357, August, 2020.Objective Infectious spondylodiscitis (IS) is rarely seen in healthy elementary school age children. Conservative treatment with antibiotics is usually preferable but sometimes fails because of the low identification rate of the pathogen by percutaneous needle biopsy. When surgical treatment is indicated, selecting the appropriate procedure is crucial in terms of invasiveness for such young children. Case report We present the case of a 9-year-old otherwise healthy girl with IS who successfully underwent debridement and identification of the causative pathogen using full endoscopic discectomy (FED) system. Methicillin-susceptible Staphylococcus aureus was identified on several cultures of samples. Immediately after the surgery, the LBP was significantly decreased and the remittent fever resolved dramatically. At the 1-year follow-up, she had no symptoms and plain radiographs showed bony fusion. Conclusion This is the first report on IS in elementary school-age children treated with the FED system. Debridement using this system could provide minimally invasive and effective curettage of the infected disc space and can be helpful in identifying the pathogen even for small children.0 Kommentare 0 Geteilt 4 Ansichten 0 Bewertungen -
Karenia selliformis is a bloom-forming toxic dinoflagellate known for production of gymnodimines (GYMs) and causing mass mortalities of marine fauna. Blooms have been reported from coastal waters of New Zealand, Mexico, Tunisia, Kuwait, Iran, China and Chile. Based on molecular phylogeny, morphology, toxin production, pigment composition and cell growth of Chilean K. selliformis isolated in 2018 (CREAN_KS01 and CREAN_KS02), this study revealed a more complex diversity within this species than previously thought. A phylogenetic reconstruction based on the large sub-unit ribosomal nucleotide (LSU rDNA) and Internal Transcriber Spacer (ITS) sequences of 12 worldwide isolates showed that within the K. selliformis clade there are at least two different phylotypes with clear phenotypic differences. Morphological differences related to the dorsal-ventral compression, shape of the hyposome and the presence of pores on the left lobe of the hyposome. A comparison of pigment signatures among worldwide isolates revealed ummer season. In conclusion, the present study provides evidence for significant genetic and phenotypic variability among worldwide isolates, which points to the existence of a K. selliformis "species complex". The massive fauna mortality during K. selliformis bloom events in the Chilean coast cannot be explained by GYMs nor brevetoxins, but can to a large extent be accounted for by the high production of long-chain PUFAs and/or still uncharacterized highly toxic compounds.Raphidiopsis raciborskii is a freshwater, potentially toxigenic cyanobacterium, originally described as a tropical species that is spreading to northern regions over several decades. The ability of R. raciborskii to produce cyanotoxins - in particular the alkaloid cylindrospermopsin (CYN), which is toxic to humans and animals - is of serious concern. The first appearance of R. raciborskii in Russia was noted in Lake Nero in the summer of 2010. This is the northernmost (57°N) recorded case of the simultaneous presence of R. https://www.selleckchem.com/products/azd9291.html raciborskii and detection of CYN. In this study, the data from long-term monitoring of the R. raciborskii population, temperature and light conditions in Lake Nero were explored. CYN and cyr/aoa genes present in environmental samples were examined using HPLC/MS-MS and PCR analysis. A R. raciborskii strain (R104) was isolated and its morphology, toxigenicity and phylogeography were studied. It is supposed that the trigger factor for the strong development of R. raciborskii in Lake Nero in suins isolated from very remote continents might be related to the ancient origin of the cyanobacterium inhabiting the united continents of Laurasia and Gondwana, rather than comparably recent transoceanic exchange between R. raciborskii populations.Blooms of harmful algae are increasing globally, yet their impacts on copepods, an important link between primary producers and higher trophic levels, remain largely unknown. Algal toxins may have direct, negative effects on the survival of copepods. They may also indirectly affect copepod survival by deterring feeding and thus decreasing the availability of energy and nutritional resources. Here we present a series of short-term (24 h) experiments in which the cosmopolitan marine copepod, Acartia tonsa, was exposed to a range of concentrations of the toxic dinoflagellate, Alexandrium catenella (strain 1119/27, formerly Alexandrium tamarense), with and without the presence of alternative, non-toxic prey (Rhodomonas sp.). We also present the toxin profile concentrations for A. catenella. The survival and feeding of A. tonsa were not affected across the range of concentrations recorded for A. catenella in the field; increased mortality of A. tonsa was only discernible when A. catenella was present at concentrations that exceed their reported environmental concentrations by two orders of magnitude. The observed lethal median concentration (LC50) for A. tonsa exposed to A. catenella was 12.45 ng STX eq L-1. We demonstrate that A. tonsa is capable of simultaneously ingesting both toxic and non-toxic algae, but increases clearance rates towards non-toxic prey as the proportional abundance of toxic A. catenella increases. The ability to actively select non-toxic algae whilst also ingesting toxic algae suggests that consumption of the latter does not cause physical incapacitation and thus does not affect ingestion in A. tonsa. This work shows that short-term exposure to toxic A. catenella is unlikely to elicit major effects on the grazing or survival of A. tonsa. However, more work is needed to understand the longer-term and sub-lethal effects of toxic algae on marine copepods.Human lactoferrin (hLF) is a glycosaminoglycan (GAG)-binding protein involved in various biological functions. It consists of two globular functional domains, referred to as the N- and C-lobes. Both heparin (HP) and heparan sulfate (HS) bind to the N-lobe domain of hLF. Although some biological functions of hLF such as neuroprotective effects and cancer growth inhibition are regulated by its binding to HS, the binding characteristics of hLF with other GAG subtypes, and their effects on biological activities are still poorly understood. Here, we report that hLF binds to chondroitin sulfate (CS)-E, a GAG subtype involved in various neurodegenerative diseases. The α-helical content of hLF, which is an indicator of changes in the secondary structure of hLF, increased in the presence of CS-C, CS-D, or CS-E, but not in the presence of HP, HS, CS-A, or CS-B. This structural change was also observed in the N-lobe, the N-terminal half region of the hLF. Additionally, the thermal stability of the N-lobe showed a dose-dependent improvement in the presence of CS-E, but not in the presence of HP. This indicates that the binding mode of hLF/N-lobe to CS-E may differ from that of HP. hLF was also found to neutralize CS-E-induced inhibition of neurite outgrowth and neuronal growth cone collapse, which are neurodegenerative responses to spinal cord injury, in cultured dorsal root ganglion neurons. Thus, hLF is a promising drug candidate for the treatment of CS-E-induced neurodegenerative diseases such as spinal cord injury.
Karenia selliformis is a bloom-forming toxic dinoflagellate known for production of gymnodimines (GYMs) and causing mass mortalities of marine fauna. Blooms have been reported from coastal waters of New Zealand, Mexico, Tunisia, Kuwait, Iran, China and Chile. Based on molecular phylogeny, morphology, toxin production, pigment composition and cell growth of Chilean K. selliformis isolated in 2018 (CREAN_KS01 and CREAN_KS02), this study revealed a more complex diversity within this species than previously thought. A phylogenetic reconstruction based on the large sub-unit ribosomal nucleotide (LSU rDNA) and Internal Transcriber Spacer (ITS) sequences of 12 worldwide isolates showed that within the K. selliformis clade there are at least two different phylotypes with clear phenotypic differences. Morphological differences related to the dorsal-ventral compression, shape of the hyposome and the presence of pores on the left lobe of the hyposome. A comparison of pigment signatures among worldwide isolates revealed ummer season. In conclusion, the present study provides evidence for significant genetic and phenotypic variability among worldwide isolates, which points to the existence of a K. selliformis "species complex". The massive fauna mortality during K. selliformis bloom events in the Chilean coast cannot be explained by GYMs nor brevetoxins, but can to a large extent be accounted for by the high production of long-chain PUFAs and/or still uncharacterized highly toxic compounds.Raphidiopsis raciborskii is a freshwater, potentially toxigenic cyanobacterium, originally described as a tropical species that is spreading to northern regions over several decades. The ability of R. raciborskii to produce cyanotoxins - in particular the alkaloid cylindrospermopsin (CYN), which is toxic to humans and animals - is of serious concern. The first appearance of R. raciborskii in Russia was noted in Lake Nero in the summer of 2010. This is the northernmost (57°N) recorded case of the simultaneous presence of R. https://www.selleckchem.com/products/azd9291.html raciborskii and detection of CYN. In this study, the data from long-term monitoring of the R. raciborskii population, temperature and light conditions in Lake Nero were explored. CYN and cyr/aoa genes present in environmental samples were examined using HPLC/MS-MS and PCR analysis. A R. raciborskii strain (R104) was isolated and its morphology, toxigenicity and phylogeography were studied. It is supposed that the trigger factor for the strong development of R. raciborskii in Lake Nero in suins isolated from very remote continents might be related to the ancient origin of the cyanobacterium inhabiting the united continents of Laurasia and Gondwana, rather than comparably recent transoceanic exchange between R. raciborskii populations.Blooms of harmful algae are increasing globally, yet their impacts on copepods, an important link between primary producers and higher trophic levels, remain largely unknown. Algal toxins may have direct, negative effects on the survival of copepods. They may also indirectly affect copepod survival by deterring feeding and thus decreasing the availability of energy and nutritional resources. Here we present a series of short-term (24 h) experiments in which the cosmopolitan marine copepod, Acartia tonsa, was exposed to a range of concentrations of the toxic dinoflagellate, Alexandrium catenella (strain 1119/27, formerly Alexandrium tamarense), with and without the presence of alternative, non-toxic prey (Rhodomonas sp.). We also present the toxin profile concentrations for A. catenella. The survival and feeding of A. tonsa were not affected across the range of concentrations recorded for A. catenella in the field; increased mortality of A. tonsa was only discernible when A. catenella was present at concentrations that exceed their reported environmental concentrations by two orders of magnitude. The observed lethal median concentration (LC50) for A. tonsa exposed to A. catenella was 12.45 ng STX eq L-1. We demonstrate that A. tonsa is capable of simultaneously ingesting both toxic and non-toxic algae, but increases clearance rates towards non-toxic prey as the proportional abundance of toxic A. catenella increases. The ability to actively select non-toxic algae whilst also ingesting toxic algae suggests that consumption of the latter does not cause physical incapacitation and thus does not affect ingestion in A. tonsa. This work shows that short-term exposure to toxic A. catenella is unlikely to elicit major effects on the grazing or survival of A. tonsa. However, more work is needed to understand the longer-term and sub-lethal effects of toxic algae on marine copepods.Human lactoferrin (hLF) is a glycosaminoglycan (GAG)-binding protein involved in various biological functions. It consists of two globular functional domains, referred to as the N- and C-lobes. Both heparin (HP) and heparan sulfate (HS) bind to the N-lobe domain of hLF. Although some biological functions of hLF such as neuroprotective effects and cancer growth inhibition are regulated by its binding to HS, the binding characteristics of hLF with other GAG subtypes, and their effects on biological activities are still poorly understood. Here, we report that hLF binds to chondroitin sulfate (CS)-E, a GAG subtype involved in various neurodegenerative diseases. The α-helical content of hLF, which is an indicator of changes in the secondary structure of hLF, increased in the presence of CS-C, CS-D, or CS-E, but not in the presence of HP, HS, CS-A, or CS-B. This structural change was also observed in the N-lobe, the N-terminal half region of the hLF. Additionally, the thermal stability of the N-lobe showed a dose-dependent improvement in the presence of CS-E, but not in the presence of HP. This indicates that the binding mode of hLF/N-lobe to CS-E may differ from that of HP. hLF was also found to neutralize CS-E-induced inhibition of neurite outgrowth and neuronal growth cone collapse, which are neurodegenerative responses to spinal cord injury, in cultured dorsal root ganglion neurons. Thus, hLF is a promising drug candidate for the treatment of CS-E-induced neurodegenerative diseases such as spinal cord injury.0 Kommentare 0 Geteilt 8 Ansichten 0 Bewertungen
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