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British Journal of Haematology Nov 2023Abnormalities of platelet function were reported in patients with severe COVID-19 (severe-C), but few data are available in patients with mild COVID-19 (mild-C) and...
Abnormalities of platelet function were reported in patients with severe COVID-19 (severe-C), but few data are available in patients with mild COVID-19 (mild-C) and after COVID-19 recovery. The aim of this study was to investigate platelet parameters in mild-C patients (n = 51), with no evidence of pneumonia, and severe-C patients (n = 49), during the acute phase and after recovery, compared to 43 healthy controls. Both mild-C and severe-C patients displayed increased circulating activated platelets, low δ-granule content (ADP, serotonin), impaired platelet activation by collagen (light transmission aggregometry) and impaired platelet thrombus formation on collagen-coated surfaces under controlled flow conditions (300/s shear rate). The observed abnormalities were more marked in severe-C patients than in mild-C patients. Overall, 61% (30/49) of mild-C and 73% (33/45) of severe-C patients displayed at least one abnormal platelet parameter. In a subgroup of just 13 patients who showed no persisting signs/symptoms of COVID-19 and were re-evaluated at least 1 month after recovery, 11 of the 13 subjects exhibited normalization of platelet parameters. In conclusion, mild abnormalities of platelet parameters were present not only in severe-C but also, albeit to a lesser extent, in mild-C patients during the acute phase of COVID-19 and normalized in most tested patients after clinical recovery.
Topics: Humans; Blood Platelets; Platelet Aggregation; COVID-19; Platelet Activation; Collagen
PubMed: 37615207
DOI: 10.1111/bjh.19062 -
Canadian Family Physician Medecin de... Dec 2023To highlight recommendations from the Canadian Thoracic Society (CTS) 2021 asthma guideline for adults and children aged 12 years and older and to address controversies... (Review)
Review
OBJECTIVE
To highlight recommendations from the Canadian Thoracic Society (CTS) 2021 asthma guideline for adults and children aged 12 years and older and to address controversies related to the update.
SOURCES OF INFORMATION
The CTS 2021 asthma guideline.
MAIN MESSAGE
Asthma is a common condition encountered in primary care. Poor symptom control and exacerbations contribute substantially to the burden of disease. Practice guidelines have been shifting in recent years toward more aggressive treatment of very mild and mild asthma, with goals of optimizing symptom control and reducing exacerbations. Consider underlying risk of exacerbation, extent of asthma symptoms, adherence levels, and treatment cost when choosing therapy for patients with very mild and mild asthma.
CONCLUSION
The goal of this article is to briefly review the evidence and rationale behind treatment options in the CTS guideline to help physicians make patient-centred decisions.
Topics: Child; Adult; Humans; Canada; Asthma; Physicians
PubMed: 38092457
DOI: 10.46747/cfp.6912829 -
EClinicalMedicine Sep 2023Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This...
BACKGROUND
Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening.
METHODS
We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR).
FINDINGS
A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively.
INTERPRETATION
Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding.
FUNDING
National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.
PubMed: 37680952
DOI: 10.1016/j.eclinm.2023.102201 -
Neural Regeneration Research Dec 2023The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment. This cognitive impairment...
The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment. This cognitive impairment is thought to result specifically from damage to the hippocampus. In this study, we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test. Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury. Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus, as well as in the density of mature dendritic spines. To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage, we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury. The differentially expressed proteins were mainly enriched in inflammation, immunity, and coagulation, suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury. In contrast, differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure, which is more consistent with neurodegeneration. We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury , and western blotting showed that, while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury, its phosphorylation level was significantly increased, which is consistent with the omics results. Administration of GRP78608, an N-methyl-D-aspartate receptor 1 antagonist, to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment. In conclusion, our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.
PubMed: 37449635
DOI: 10.4103/1673-5374.374654 -
Journal of Animal Science and... Sep 2023Rises in global warming and extreme weather occurrence make the risk of heat stress (HS) induced by high ambient temperatures more likely in high-yielding dairy cows,...
BACKGROUND
Rises in global warming and extreme weather occurrence make the risk of heat stress (HS) induced by high ambient temperatures more likely in high-yielding dairy cows, resulting in low milk quality and yield. In animals, oxygen is involved in many physiological and metabolic processes, but the effects of HS on oxygen metabolism remain unclear. Thus, the current study aimed to investigate how oxygen metabolism plays a role in health status of dairy cows by measuring the milk yield, milk composition, and blood biochemical variables of cows under different levels of HS: none (No-HS), mild (Mild-HS), and moderate HS (Mod-HS).
RESULTS
The HS significantly increased rectal temperature (P < 0.01) and respiration rate (P < 0.01). Under Mod-HS, greater Na (P < 0.05) and lower total CO, and pH (P < 0.05) were observed relative to those under No-HS and Mild-HS. Oxygen concentrations in both coccygeal artery and mammary vein (P < 0.01) were lower under Mod-HS than under No-HS. Coccygeal vein concentrations of heat shock protein 90 (HSP90) (P < 0.05) increased during Mod-HS compared with those in cows under No-HS. Malondialdehyde increased during Mod-HS, and glutathione peroxidase (P < 0.01) increased during Mild-HS. Coccygeal vein concentrations of vascular endothelial growth factor (P < 0.01), heme oxygenase-1 (P < 0.01), and hypoxia-inducible factor 1α (P < 0.01) were greater in cows under Mod-HS than those under No-HS. Red blood cell count (P < 0.01) and hemoglobin concentration (P < 0.01) were lower in the coccygeal vein of dairy cows under Mild- and Mod-HS than those of cows under No-HS.
CONCLUSIONS
Exposure to HS negatively impacts the health status and lactation performance of dairy cows by limiting oxygen metabolism and transportation. However, the specific mechanism by which HS affects mammary function in cows remains unclear and requires further exploration.
PubMed: 37658441
DOI: 10.1186/s40104-023-00915-3 -
The Journal of Maternal-fetal &... Dec 2023Prenatal diagnosis and counseling of isolated ventriculomegaly (VM) represent a considerable challenge. We aimed to analyze the intrauterine evolution, associated...
INTRODUCTION
Prenatal diagnosis and counseling of isolated ventriculomegaly (VM) represent a considerable challenge. We aimed to analyze the intrauterine evolution, associated anomalies, and neurodevelopmental outcome using the Battelle Development Inventory (BDI) of fetuses with an initial diagnosis of isolated mild VM.
MATERIAL AND METHODS
Retrospective cohort study of fetuses diagnosed with mild isolated VM (10 -12 mm) between 2012 and 2016 in a tertiary hospital. In 2018, parents were invited to complete the structured BDI test for the neurodevelopmental evaluation of their children in five domains (personal-social skills, adaptive behavior, psychomotor ability, communication, and cognition). Results exceeding two standard deviations were considered abnormal and referred to an expert neuropediatrician.
RESULTS
We identified 43 cases of mild isolated VM. In 5 (11%), structural abnormalities were detected during prenatal follow-up, being related to non-regressive forms ( = .01) and bilateral VM ( = .04). The BDI test was completed by 19/43 (44%). The global score was abnormal in 10/19 (53%). Of them, the neuropediatrician confirmed a neurodevelopmental delay solely in 3 cases that had already been diagnosed with neurological disorders. The most affected domains were gross motor skills (63%), personal-social (63%), and adaptive domains (47%). Communicative and cognitive areas were abnormal in 26% of cases.
CONCLUSION
In fetuses with isolated mild VM detected in the second half of pregnancy, 53% had an abnormal BDI test at 2-6 years, but a neurological disorder was only confirmed in the 30% of them.
Topics: Pregnancy; Child; Female; Humans; Retrospective Studies; Ultrasonography, Prenatal; Hydrocephalus; Prenatal Diagnosis; Fetus; Nervous System Malformations; Pregnancy Outcome; Magnetic Resonance Imaging
PubMed: 37217456
DOI: 10.1080/14767058.2023.2214836 -
Journal of Nanobiotechnology Dec 2023The present work was an endeavor to shed light on how mild photothermia possibly synergizes with immune checkpoint inhibition for tumor therapy. We established mild...
The present work was an endeavor to shed light on how mild photothermia possibly synergizes with immune checkpoint inhibition for tumor therapy. We established mild photothermal heating protocols to generate temperatures of 43 °C and 45 °C in both in vitro and in vivo mouse 4T1 triple-negative breast cancer (TNBC) models using polyglycerol-coated carbon nanohorns (CNH-PG) and 808 nm laser irradiation. Next, we found that 1) CNH-PG-mediated mild photothermia (CNH-PG-mPT) significantly increased expression of the immune checkpoint PD-L1 and type-1 macrophage (M1) markers in the TNBC tumors; 2) CNH-PG-mPT had a lower level of anti-tumor efficacy which was markedly potentiated by BMS-1, a PD-L1 blocker. These observations prompted us to explore the synergetic mechanisms of CNH-PG-mPT and BMS-1 in the context of tumor cell-macrophage interactions mediated by PD-L1 since tumor-associated macrophages (TAMs) are a major source of PD-L1 expression in tumors. In vitro, the study then identified two dimensions where BMS-1 potentiated CNH-PG-mPT. First, CNH-PG-mPT induced PD-L1 upregulation in the tumor cells and showed a low level of cytotoxicity which was potentiated by BMS-1. Second, CNH-PG-mPT skewed TAMs towards an M1-like anti-tumor phenotype with upregulated PD-L1, and BMS-1 bolstered the M1-like phenotype. The synergistic effects of BMS-1 and CNH-PG-mPT both on the tumor cells and TAMs were more pronounced when the two cell populations were in co-culture. Further in vivo study confirmed PD-L1 upregulation both in tumor cells and TAMs in the TNBC tumors following treatment of CNH-PG-mPT. Significantly, TAMs depletion largely abolished the anti-TNBC efficacy of CNH-PG-mPT alone and in synergy with BMS-1. Collectively, our findings reveal PD-L1 upregulation to be a key response of TNBC to mild photothermal stress, which plays a pro-survival role in the tumor cells while also acting as a brake on the M1-like activation of the TAMs. Blockade of mPT‑induced PD‑L1 achieves synergistic anti-TNBC efficacy by taking the intrinsic survival edge off the tumor cells on one hand and taking the brakes off the M1-like TAMs on the other. Our findings reveal a novel way (i.e. mild thermia plus PD-L1 blockade) to modulate the TAMs-tumor cell interaction to instigate a mutiny of the TAMs against their host tumor cells.
Topics: Humans; Animals; Mice; Triple Negative Breast Neoplasms; B7-H1 Antigen; Photothermal Therapy; Macrophages; Phenotype; Cell Line, Tumor
PubMed: 38082443
DOI: 10.1186/s12951-023-02240-3 -
Sexual Medicine Jun 2023Increased carotid artery intima-media thickness (CIMT) has been shown to be associated with erectile dysfunction (ED), but studies evaluating the efficacy of CIMT in... (Review)
Review
BACKGROUND
Increased carotid artery intima-media thickness (CIMT) has been shown to be associated with erectile dysfunction (ED), but studies evaluating the efficacy of CIMT in predicting drug response are lacking in the literature.
AIM
We aimed to evaluate the efficacy of CIMT in predicting the response to phosphodiesterase-5 inhibitors (PDE5-I).
METHODS
A total of 274 subjects were divided into two groups: ED patients ( = 150) and controls ( = 124). The patients in the ED group were further divided into the subgroups of severe, moderate, mild-moderate, and mild ED. Blood tests, carotid ultrasonography, and the International Index of Erectile Function-5 (IIEF-5) diagnostic tool were applied to all subjects. Tadalafil was administered to each patient. The patients were re-evaluated using the IIEF-5 questionnaire after 2 months of treatment. According to their response to medication, the patients were evaluated as responders or nonresponders.
OUTCOMES
Increased CIMT was significantly associated with the failure of PDE5-I therapy, especially in patients with moderate/mild-moderate ED.
RESULTS
Fasting blood glucose, body mass index, and CIMT were significantly higher in the ED group compared to the control group ( .021, = .006, and < .001, respectively). The IIEF-5 score was significantly lower in the ED group ( < .001). CIMT was significantly correlated with the IIEF-5 score. When the total patient group was evaluated, the CIMT value of the responders was significantly lower than that of the nonresponders ( = .001). CIMT was significantly higher among the nonresponders with moderate/mild-moderate ED compared to the responders ( = .004 and .008, respectively), while there was no significant difference in CIMT between the responders and nonresponders with severe or mild ED. A receiver operating characteristic (ROC) analysis of CIMT was performed for discrimination between nonresponders and responders with moderate/mild-moderate ED. The area under the ROC curve was 0.801 (0.682-0.921) ( = .001), and the cutoff value was determined to be 0.825 mm, at which CIMT predicted the response to treatment with 65% sensitivity and 89% specificity.
CLINICAL IMPLICATIONS
Using a validated CIMT cutoff value can help the physician inform the patient about the possibility of drug failure and avoid attempting second-line therapy too soon.
STRENGTHS AND LIMITATIONS
There are three main limitations to our study. First, the number of participants was low. Second, ultrasound is a relatively subjective method, and third, all measurements were made by the same radiologist.
CONCLUSION
CIMT can be used as a predictor of response to PDE5-I therapies in patients with moderate/mild-moderate ED.
PubMed: 37529683
DOI: 10.1093/sexmed/qfad042 -
Brain Communications 2023Recent evidence shows that identifying and treating epileptiform abnormalities in patients with Alzheimer's disease could represent a potential avenue to improve...
Recent evidence shows that identifying and treating epileptiform abnormalities in patients with Alzheimer's disease could represent a potential avenue to improve clinical outcome. Specifically, animal and human studies have revealed that in the early phase of Alzheimer's disease, there is an increased risk of seizures. It has also been demonstrated that the administration of anti-seizure medications can slow the functional progression of the disease only in patients with EEG signs of cortical hyperexcitability. In addition, although it is not known at what disease stage hyperexcitability emerges, there remains no consensus regarding the imaging and diagnostic methods best able to detect interictal events to further distinguish different phenotypes of Alzheimer's disease. In this exploratory work, we studied 13 subjects with amnestic mild cognitive impairment and 20 healthy controls using overnight high-density EEG with 256 channels. All participants also underwent MRI and neuropsychological assessment. Electronic source reconstruction was also used to better select and localize spikes. We found spikes in six of 13 (46%) amnestic mild cognitive impairment compared with two of 20 (10%) healthy control participants ( = 0.035), representing a spike prevalence similar to that detected in previous studies of patients with early-stage Alzheimer's disease. The interictal events were low-amplitude temporal spikes more prevalent during non-rapid eye movement sleep. No statistically significant differences were found in cognitive performance between amnestic mild cognitive impairment patients with and without spikes, but a trend in immediate and delayed memory was observed. Moreover, no imaging findings of cortical and subcortical atrophy were found between amnestic mild cognitive impairment participants with and without epileptiform spikes. In summary, our exploratory study shows that patients with amnestic mild cognitive impairment reveal EEG signs of hyperexcitability early in the disease course, while no other significant differences in neuropsychological or imaging features were observed among the subgroups. If confirmed with longitudinal data, these exploratory findings could represent one of the first signatures of a preclinical epileptiform phenotype of amnestic mild cognitive impairment and its progression.
PubMed: 37965047
DOI: 10.1093/braincomms/fcad302 -
Alzheimer's Research & Therapy Jan 2024Disease-modifying treatments for Alzheimer's disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not... (Review)
Review
BACKGROUND
Disease-modifying treatments for Alzheimer's disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as the Digital Clock and Recall (DCR™), have the potential to address this need. Here, we examine the advantages of DCR over the Mini-Mental State Examination (MMSE) in detecting mild cognitive impairment (MCI) and mild dementia.
METHODS
We studied 706 participants from the multisite Bio-Hermes study (age mean ± SD = 71.5 ± 6.7; 58.9% female; years of education mean ± SD = 15.4 ± 2.7; primary language English), classified as cognitively unimpaired (CU; n = 360), mild cognitive impairment (MCI; n = 234), or probable mild Alzheimer's dementia (pAD; n = 111) based on a review of medical history with selected cognitive and imaging tests. We evaluated cognitive classifications (MCI and early dementia) based on the DCR and the MMSE against cohorts based on the results of the Rey Auditory Verbal Learning Test (RAVLT), the Trail Making Test-Part B (TMT-B), and the Functional Activities Questionnaire (FAQ). We also compared the influence of demographic variables such as race (White vs. Non-White), ethnicity (Hispanic vs. Non-Hispanic), and level of education (≥ 15 years vs. < 15 years) on the DCR and MMSE scores.
RESULTS
The DCR was superior on average to the MMSE in classifying mild cognitive impairment and early dementia, AUC = 0.70 for the DCR vs. 0.63 for the MMSE. DCR administration was also significantly faster (completed in less than 3 min regardless of cognitive status and age). Among 104 individuals who were labeled as "cognitively unimpaired" by the MMSE (score ≥ 28) but actually had verbal memory impairment as confirmed by the RAVLT, the DCR identified 84 (80.7%) as impaired. Moreover, the DCR score was significantly less biased by ethnicity than the MMSE, with no significant difference in the DCR score between Hispanic and non-Hispanic individuals.
CONCLUSIONS
DCR outperforms the MMSE in detecting and classifying cognitive impairment-in a fraction of the time-while being not influenced by a patient's ethnicity. The results support the utility of DCR as a sensitive and efficient cognitive assessment in primary care settings.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT04733989.
Topics: Humans; Female; Male; Dementia; Cognitive Dysfunction; Alzheimer Disease; Mental Status and Dementia Tests; Neuropsychological Tests
PubMed: 38167251
DOI: 10.1186/s13195-023-01367-7