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1.
Biomater Sci ; 12(19): 5091-5104, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39219491

ABSTRACT

Due to their rapid spread, high variability, and drug-resistant strains, new viral infections are continuously emerging. A lack of effective antiviral drugs and vaccines, resulting in disease and death, has significant socioeconomic consequences. Hemoperfusion can effectively adsorb and remove toxins from the blood, thus purifying the blood and serving as an acute treatment. Therefore, the aim of this study was to construct adsorbents to selectively remove viruses from the blood to quickly treat pathogen infection. We reported on new metal-organic framework (MOF)-polymer beads based on MIL-53(Al) and cellulose acetate (CNC), which were prepared by a one-step phase inversion method and applied as a viral hemo-adsorbent for the first time. The characterization results demonstrated that MIL-53(Al) was well dispersed in the CNC matrix. The adsorption results demonstrated that the capture efficiency of the human immunodeficiency virus (HIV) could exceed 99.93%, and the corresponding infectious titer decreased by approximately 103 times in clinical application. Moreover, CNC/MIL-53 exhibited low hemolysis ratios and good anticoagulant properties. Furthermore, molecular dynamics simulations revealed that the interplay of hydrogen bonding was the governing physisorption mechanism. Overall, CNC/MIL-53 could serve as a new type of hemoperfusion adsorbent for virus removal from blood and provide a new treatment pathway to mitigate epidemics.


Subject(s)
Cellulose , Metal-Organic Frameworks , Cellulose/chemistry , Cellulose/analogs & derivatives , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Adsorption , Humans , Porosity , Molecular Dynamics Simulation , Hemoperfusion/methods , Animals
2.
J Stroke Cerebrovasc Dis ; : 108016, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39299664

ABSTRACT

BACKGROUND: Although assessment of frailty is increasingly being included in routine practice, its effects on hospital outcomes is not well studied. In this study, we used a national database to estimate the effects of frailty on hospital outcomes among stroke patients. METHODS: This study was a retrospective analysis of data from Nationwide Inpatient Sample (NIS) database collected during the years 2016 to 2019. Adult patients 45 years and older with a primary diagnosis of stroke were included for the analysis. Primary outcome was frequency of frailty among stroke patients. Secondary outcomes were in-hospital mortality, prolonged length of stay, mechanical ventilation, and acute renal failure. Frailty levels were assessed by using the Hospital Frailty Risk Score (HFRS). RESULTS: Among 2,031,085 stroke hospitalizations, 362,140 (17.8%) were non-frail, 1,333,000 (65.6%) were pre-frail, and 335,945 (16.6%) were frail. Regression analysis showed that the odds of mortality were significantly higher among frail (aOR, 2.82, 95% CI: 2.63-3.04) and pre-frail (aOR, 1.62, 95% CI: 1.53-1.73) patients, compared to non-frail patients. Similarly, the odds of mechanical ventilation were significantly higher among frail (aOR, 9.72, 95% CI: 8.84-10.69) and pre-frail (aOR, 3.41, 95% CI: 3.12-3.73) patients. The odds of acute renal failure were significantly higher among frail (aOR, 6.96, 95% CI: 6.62-7.33) and pre-frail (aOR, 2.94, 95% CI: 2.80-3.08) patients. CONCLUSION: Collaborative efforts by neurologists, neurosurgeons, and physiatrists towards identifying frailty and incorporating it in risk estimation measures could help improve management strategies, resource utilization, and optimization of patient outcomes among frail stroke patients.

3.
Sci Rep ; 14(1): 18188, 2024 08 06.
Article in English | MEDLINE | ID: mdl-39107366

ABSTRACT

Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.


Subject(s)
Fecal Microbiota Transplantation , Lactobacillus , Humans , Fecal Microbiota Transplantation/methods , Adult , Adolescent , Female , Male , Young Adult , Double-Blind Method , Inflammatory Bowel Diseases/therapy , Inflammatory Bowel Diseases/microbiology , Gastrointestinal Microbiome , Pilot Projects , Feces/microbiology , Treatment Outcome , Crohn Disease/therapy , Crohn Disease/microbiology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Colitis, Ulcerative/therapy , Colitis, Ulcerative/microbiology
4.
ACS Appl Mater Interfaces ; 16(31): 41321-41331, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39051622

ABSTRACT

The clearance of urea poses a formidable challenge, and its excessive accumulation can cause various renal diseases. Urease demonstrates remarkable efficacy in eliminating urea, but cannot be reused. This study aimed to develop a composite vector system comprising microcrystalline cellulose (MCC) immobilized with urease and metal-organic framework (MOF) UiO-66-NH2, denoted as MCC@UiO/U, through the dynamic defect generation strategy. By utilizing competitive coordination, effective immobilization of urease into MCC@UiO was achieved for efficient urea removal. Within 2 h, the urea removal efficiency could reach up to 1500 mg/g, surpassing an 80% clearance rate. Furthermore, an 80% clearance rate can also be attained in peritoneal dialyzate from patients. MCC@UiO/U also exhibits an exceptional bioactivity even after undergoing 5 cycles of perfusion, demonstrating remarkable stability and biocompatibility. This innovative approach and methodology provide a novel avenue and a wide range of immobilized enzyme vectors for clinical urea removal and treatment of kidney diseases, presenting immense potential for future clinical applications.


Subject(s)
Cellulose , Enzymes, Immobilized , Metal-Organic Frameworks , Urea , Urease , Urease/chemistry , Urease/metabolism , Urea/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Cellulose/chemistry , Metal-Organic Frameworks/chemistry , Humans
5.
J Neurooncol ; 169(1): 105-117, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38837019

ABSTRACT

INTRODUCTION: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). METHODS: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data. RESULTS: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology. CONCLUSION: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.


Subject(s)
Brain Neoplasms , Radiosurgery , Humans , Radiosurgery/methods , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Brain Neoplasms/radiotherapy , Brain Neoplasms/mortality , Female , Male , Middle Aged , Aged , Retrospective Studies , Adult , Treatment Outcome , Survival Rate , Follow-Up Studies
6.
Ann Epidemiol ; 94: 81-90, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710239

ABSTRACT

PURPOSE: Identifying predictors of opioid overdose following release from prison is critical for opioid overdose prevention. METHODS: We leveraged an individually linked, state-wide database from 2015-2020 to predict the risk of opioid overdose within 90 days of release from Massachusetts state prisons. We developed two decision tree modeling schemes: a model fit on all individuals with a single weight for those that experienced an opioid overdose and models stratified by race/ethnicity. We compared the performance of each model using several performance measures and identified factors that were most predictive of opioid overdose within racial/ethnic groups and across models. RESULTS: We found that out of 44,246 prison releases in Massachusetts between 2015-2020, 2237 (5.1%) resulted in opioid overdose in the 90 days following release. The performance of the two predictive models varied. The single weight model had high sensitivity (79%) and low specificity (56%) for predicting opioid overdose and was more sensitive for White non-Hispanic individuals (sensitivity = 84%) than for racial/ethnic minority individuals. CONCLUSIONS: Stratified models had better balanced performance metrics for both White non-Hispanic and racial/ethnic minority groups and identified different predictors of overdose between racial/ethnic groups. Across racial/ethnic groups and models, involuntary commitment (involuntary treatment for alcohol/substance use disorder) was an important predictor of opioid overdose.


Subject(s)
Decision Trees , Opiate Overdose , Adult , Female , Humans , Male , Middle Aged , Young Adult , Analgesics, Opioid/poisoning , Analgesics, Opioid/adverse effects , Ethnicity/statistics & numerical data , Massachusetts/epidemiology , Opiate Overdose/epidemiology , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/ethnology , Prisoners/statistics & numerical data , Prisons/statistics & numerical data , White , Racial Groups
7.
Clin Transl Gastroenterol ; 15(9): e1, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38624107

ABSTRACT

INTRODUCTION: Proton pump inhibitor (PPI) use has been associated with an increased risk of gastrointestinal and upper respiratory infections in children. There are limited longitudinal data on the effect of PPI in children. The goal of this prospective observational study was to compare the stool and oropharyngeal microbiome of children before and after starting PPIs. METHODS: We prospectively recruited participants from a gastroenterology clinic. Consented participants provided stool samples and oropharyngeal swabs at baseline and after 8 weeks of PPI therapy. Microbiome changes were measured by analyzing 16S sequencing from both body sites at both time points. RESULTS: Thirty-four participants completed the study and provided samples both at baseline and after 8 weeks on PPI therapy. Of those, 24 participants had sufficient sequencing from both stool and oropharyngeal samples at both time points. There were no differences between the pre-PPI and post-PPI samples using beta-diversity metrics in either the oropharynx or stool. There were, however, significant changes in specific taxa. There was an enrichment of Streptococcus in the stool after PPI use and a reduction in the relative abundance of Bifidobacterium , Peptostreptococcus , and Turicibacter ( P -values < 0.01). Furthermore, there was an increase in the relative abundance of oropharyngeal bacteria in the stool after PPI therapy. This enrichment of oropharyngeal bacteria in the stool was most prominent in younger participants. DISCUSSION: Further investigation is needed to determine the clinical and microbial factors that predispose or protect against microbiome changes due to PPI use and why young children are more susceptible to this PPI effect.


Subject(s)
Feces , Oropharynx , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/administration & dosage , Male , Female , Child , Prospective Studies , Oropharynx/microbiology , Feces/microbiology , Adolescent , Longitudinal Studies , Child, Preschool , Gastrointestinal Microbiome/drug effects , RNA, Ribosomal, 16S/genetics , Microbiota/drug effects , Bacteria/isolation & purification , Bacteria/drug effects , Bacteria/genetics
8.
ACS Biomater Sci Eng ; 10(3): 1494-1506, 2024 03 11.
Article in English | MEDLINE | ID: mdl-38414275

ABSTRACT

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.


Subject(s)
Bacterial Infections , Hemoperfusion , Liver Failure , Nanocomposites , Humans , Bilirubin/chemistry , Polystyrenes/chemistry , Hemoperfusion/methods , Nanocomposites/therapeutic use
9.
Curr Mol Pharmacol ; 17: e18761429282063, 2024.
Article in English | MEDLINE | ID: mdl-38389418

ABSTRACT

BACKGROUND: Nicosulfuron, a widely used herbicide in crops, has raised concerns due to its escalating presence as an environmental pollutant, particularly in soil and water. The potential adverse effects of nicosulfuron on animals, including reproductive toxicity, have garnered attention. OBJECTIVE: The study aimed to evaluate the reproductive toxicity of nicosulfuron in male mice. METHODS: Male mice were orally administrated with three different concentration gradients (350, 700, and 1400 mg/kg) of nicosulfuron for 35 days. The investigation delved into sperm quality, testicular structures, and expression of cleaved caspase-3 and NF-κB p65 of the testes. RESULTS: The finding unveiled a correlation between nicosulfuron exposure and detrimental effects on sperm quality and alteration of testicular structure. Notably, parameters, such as sperm survival rate (SUR) and sperm motility (MOT), exhibited a decline in relation to increasing nicosulfuron dosages. Moreover, in the mice subjected to higher doses of nicosulfuron, elevated expression of cleaved caspase-3 and NF-κB p65 was observed in the testes. Interestingly, we also observed an increase of NF-κB p65 expression in the mice exposed to the nicosulfuron. CONCLUSION: Our research revealed that exposure to nicosulfuron resulted in compromised sperm quality and alterations in testicular structure. The correlation between nicosulfuron and apoptosis, especially via the NF-κB pathway, provided significant insights into the mechanisms underpinning these detrimental effects. These findings significantly enhance our comprehension of the potential hazards associated with nicosulfuron exposure and its impacts on the reproductive health of animals.


Subject(s)
NF-kappa B , Pyridines , Sulfonylurea Compounds , Testis , Male , Mice , Animals , NF-kappa B/metabolism , Caspase 3/metabolism , Caspase 3/pharmacology , Oxidative Stress , Sperm Motility , Semen/metabolism , Spermatozoa/metabolism , Signal Transduction , Apoptosis
10.
South Med J ; 117(2): 75-79, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38307502

ABSTRACT

OBJECTIVES: Many epidemiological studies have shown that coronavirus disease 2019 (COVID-19) disproportionately affects males, compared with females, although other studies show that there were no such differences. The aim of the present study was to assess differences in the prevalence of hospitalizations and in-hospital outcomes between the sexes, using a larger administrative database. METHODS: We used the 2020 California State Inpatient Database for this retrospective analysis. International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code U07.1 was used to identify COVID-19 hospitalizations. These hospitalizations were subsequently stratified by male and female sex. Diagnosis and procedures were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. The primary outcome of the study was hospitalization rate, and secondary outcomes were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and intensive care unit (ICU) admission. RESULTS: There were 95,180 COVID-19 hospitalizations among patients 18 years and older, 52,465 (55.1%) of which were among men and 42,715 (44.9%) were among women. In-hospital mortality (12.4% vs 10.1%), prolonged length of hospital stays (30.6% vs 25.8%), vasopressor use (2.6% vs 1.6%), mechanical ventilation (11.8% vs 8.0%), and ICU admission rates (11.4% versus 7.8%) were significantly higher among male compared with female hospitalizations. Conditional logistic regression analysis showed that the odds of mortality (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.38-1.44), hospital lengths of stay (OR 1.35, 95% CI 1.31-1.39), vasopressor use (OR 1.59, 95% CI 1.51-1.66), mechanical ventilation (OR 1.62, 95% CI 1.47-1.78), and ICU admission rates (OR 1.58, 95% CI 1.51-1.66) were significantly higher among male hospitalizations. CONCLUSION: Our findings show that male sex is an independent and strong risk factor associated with COVID-19 severity.


Subject(s)
COVID-19 , Humans , Male , Female , COVID-19/epidemiology , COVID-19/therapy , Retrospective Studies , Sex Factors , Hospitalization , Intensive Care Units , Hospitals , Hospital Mortality
11.
Article in English | MEDLINE | ID: mdl-37840193

ABSTRACT

College students who experienced somatic symptoms during the COVID-19 pandemic may engage in rumination, but their bidirectional nature remains underexplored. Symptom perception theory suggests a reciprocal relationship between rumination and somatic symptoms, and the multiple-stressor perspective and the perseverative cognition hypothesis assume that the reciprocal association might be exacerbated by high stress. In this study, we examined temporal associations between rumination and somatic symptoms and variations by patterns of stress related to COVID-19 and daily hassles. A total of 582 Chinese college students provided daily reports on rumination, somatic symptoms, COVID-related stress, and daily hassles for seven consecutive days in November 2020. A cross-lagged panel model showed a positive reciprocal association between rumination and somatic symptoms. Greater rumination predicted more next-day somatic symptoms, and more somatic symptoms increased next-day rumination. Dual trajectory analysis identified four stress patterns of COVID-related stress and daily hassles (i.e. low-low, low-high, high-low, and high-high), and multi-group analysis found the reciprocal association only presented in the high-high group. Our findings indicate a vicious circle between rumination and somatic symptoms that is dependent on heterogeneous stress patterns. Attention should be paid to the high-risk group with both high levels of COVID-related stress and daily hassles.

12.
Am J Cardiol ; 203: 169-174, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37499596

ABSTRACT

Transthyretin amyloid cardiomyopathy is being increasingly recognized as an important cause of heart failure (HF). In this study, we looked at adverse outcomes in hospitalizations with amyloid-related HF. This study was a retrospective analysis of the National Inpatient Sample data, collected from 2016 to 2019. Patients ≥41 years of age and admitted for HF were included in the study. In these hospitalizations, amyloid-related HF was identified through the International Classification of Diseases, Tenth Revision, Clinical Modification codes for amyloidosis. The primary outcome of the study was in-hospital mortality, whereas secondary outcomes were prolonged length of stay, mechanical ventilation, mechanical circulatory support, vasopressors use, and dispositions other than home. From 2016 to 2019, there were 4,705,274 HF hospitalizations, of which 16,955 (0.4%) had amyloid cardiomyopathy. In all HF hospitalizations, amyloid-related increased from 0.26% in 2016 to 0.46% in 2019 (relative increase, 76.9%, P for trend <0.001). Amyloid-related HF hospitalizations were more common in older, male, and Black patients. The odds of in-hospital mortality (odds ratio [OR], 1.29; 95% confidence interval [CI]: 1.11 to 1.38), prolonged hospital length (OR, 1.61; 95% CI: 1.49 to 1.73) and vasopressors use (OR, 1.59; 95% CI: 1.23 to 2.05) were significantly higher for amyloid-related hospitalizations. Amyloid-related HF hospitalizations are increasing substantially and are associated with adverse hospital outcomes. These hospitalizations were disproportionately higher for older, male, and Black patients. Amyloid-related HF is rare and underdiagnosed yet has several adverse outcomes. Hence, healthcare providers should be watchful of this condition for early identification and prompt management.


Subject(s)
Cardiomyopathies , Heart Failure , Humans , Male , Aged , Retrospective Studies , Hospitalization , Heart Failure/epidemiology , Heart Failure/therapy , Heart Failure/complications , Risk Assessment , Cardiomyopathies/complications , Hospital Mortality
13.
Anal Chem ; 95(32): 11885-11891, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37348197

ABSTRACT

As a biomarker of hepatocellular carcinoma (HCC) biopsy, circulating tumor cells (CTCs) are often used in the diagnosis of cancer and treatment guidance. For CTCs detection, immuno-magnetic nanoparticles (IMNs) are one of the most commonly used platforms. However, the nonspecific adsorption of proteins and non-tumor cells weakens the performance of IMNs to capture CTCs. In this work, we developed an IMNs platform which was constructed by a biomimetic protein corona precoating and a polyethylene glycol (PEG) spacer to form the PEG and corona-coated IMNs (IP-CMNs). Due to the dual stealth effect of protein corona precoating and PEG spacer, the nonspecific protein adsorption and cell binding of P-CMNs could reduce by ∼5.5- and ∼5.4-fold, respectively, compared with those of unmodified particles. Furthermore, the PEG spacer could not only reduce the interaction between IP-CMNs and leukocytes but also enhance the capture performance toward tumor cells. By using artificial blood samples, the capture efficiency of IP-CMNs toward rare CTCs was found to be 88.3%, while it was 70.5% by using commercial IMNs. Finally, CTCs were successfully isolated in all HCC patient blood samples (7/7) using IP-CMNs. These results provide insight into the use of the multifunctional nanoplatform as a useful tool for CTCs detection.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Neoplastic Cells, Circulating , Protein Corona , Humans , Carcinoma, Hepatocellular/diagnosis , MCF-7 Cells , Neoplastic Cells, Circulating/pathology , Liver Neoplasms/diagnosis , Polyethylene Glycols , Cell Separation
14.
J Youth Adolesc ; 52(9): 1873-1886, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37296270

ABSTRACT

There is growing evidence of a clear association between students' perceived stress and their adjustment to life at college. However, the predictors and implications of distinct changing patterns of perceived stress during the transition to college life are less clear. To address these research gaps, the current study aims to identify distinct patterns of perceived stress trajectories among 582 Chinese first-year college students (Mage = 18.11, SDage = 0.65; 69.40% female) across the first 6 months upon enrollment. Three distinct profiles of perceived stress trajectories, i.e., low-stable (15.63%), middle-decreasing (69.07%), and high-decreasing (15.29%), were identified. Moreover, individuals who followed the low-stable trajectory showed better distal outcomes (specifically, higher levels of well-being and academic adjustment) 8 months after enrollment than those who followed the other two trajectories. Furthermore, two types of positive mindset (a growth mindset of intelligence and a stress-is-enhancing mindset) contributed to differences in perceived stress trajectory, either independently or jointly. These findings highlight the significance of identifying different patterns of perceived stress among students during the transition to college, as well as the protective roles of both a stress mindset and a mindset of intelligence.


Subject(s)
Intelligence , Students , Adolescent , Female , Humans , Male , Asian People , Stress, Psychological , Universities , Adaptation, Psychological
16.
Reproduction ; 166(1): 27-36, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37140983

ABSTRACT

In brief: The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes. Abstract: Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.


Subject(s)
Infertility, Male , Obesity, Morbid , Humans , Male , Mice , Animals , Obesity, Morbid/complications , Obesity, Morbid/metabolism , Mice, Obese , Sperm Motility , Mice, Inbred C57BL , Obesity/complications , Obesity/metabolism , Testis/metabolism , Infertility, Male/etiology , Infertility, Male/metabolism , Oxidative Stress , Apoptosis , Glycolysis
18.
medRxiv ; 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36778473

ABSTRACT

Background: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent Clostridioides difficile infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Results: Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. The treatment arm received seven days of antibiotics followed by FMT enema and then capsules weekly for seven weeks. We enrolled four subjects with CD and 11 with UC, ages 14-29 years. Due to weekly stool sampling, we were able to create a time series of alpha diversity, beta diversity and engraftment as they related to clinical response. Subjects exhibited a wide range of microbial diversity and donor engraftment as FMT progressed. Specifically, engraftment ranged from 26% to 90% at week 2 and 3% to 92% at two months. Consistent with the current literature, increases over time of both alpha diversity (p< 0.05) and donor engraftment (p< 0.05) correlated with improved clinical response. Additionally, our weekly time series enabled an investigation into the clinical and microbial correlates of engraftment at various time points. We discovered that the post-antibiotic but pre-FMT time point, often overlooked in FMT trials, was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial with publicly available weekly sequencing data. Conclusions: We found that higher residual alpha diversity and Lactobacillus blooms after antibiotic treatment correlated with improved engraftment and clinical response to FMT. Future studies should closely examine the host microbial communities pre-FMT and the impact of antibiotic preconditioning on engraftment and response.

19.
Curr Psychol ; : 1-15, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36468161

ABSTRACT

Drastically disrupting daily routines, the global pandemic of COVID-19 has posed critical mental health threats to adolescents and young adults worldwide. Many of the extant empirical findings, however, have focused on individuals' psychological adjustment during the initial phase of the pandemic. It is less clear how COVID-19 stressful experiences impact young people's daily lives in the post-pandemic "new normal." Drawing on 7-day diary reports, the present study fills this gap by examining: (1) how daily perceived stress impacted daily emotional adjustment; and (2) the moderating effects of COVID-19 stressful experiences on these associations among 582 Chinese young adults (M age = 18.12, SD = .65; 69% females). Results indicated that higher levels of both trait (i.e., average levels) and state (i.e., daily fluctuations) perceived stress were associated with greater negative and anxious moods, and that prior pandemic-related experiences exacerbated the adverse impact of both trait and state perceived stress on daily moods. Specifically, young adults reporting greater COVID-19 stressful experiences demonstrated poorer emotional adjustment (i.e., lower levels of positive mood and higher levels of negative mood) on days when they had more fluctuations in perceived stress; the aggravating impact was stronger when the average levels of perceived stress were higher. By illuminating the moderating effects of COVID-19 stressful experiences, this study contributes to the limited, but burgeoning, research examining the prolonged impact of the COVID-19 health crisis on daily emotional adjustment in post-pandemic life.

20.
Sci Rep ; 12(1): 17781, 2022 10 22.
Article in English | MEDLINE | ID: mdl-36273031

ABSTRACT

Microfluidic devices that combine an extracellular matrix environment, cells, and physiologically relevant perfusion, are advantageous as cell culture platforms. We developed a hydrogel-based, microfluidic cell culture platform by loading polyethylene glycol (PEG) hydrogel-encapsulated U87 glioblastoma cells into membrane-capped wells in polydimethyl siloxane (PDMS). The multilayer microfluidic cell culture system combines previously reported design features in a configuration that loads and biomimetically perfuses a 2D array of cell culture chambers. One dimension of the array is fed by a microfluidic concentration gradient generator (MCGG) while the orthogonal dimension provides loading channels that fill rows of cell culture chambers in a separate layer. In contrast to typical tree-like MCGG mixers, a fractional serial dilution of 1, ½, », and 0 of the initial solute concentration is achieved by tailoring the input microchannel widths. Hydrogels are efficiently and reproducibly loaded in all wells and cells are evenly distributed throughout the hydrogel, maintaining > 90% viability for up to 4 days. In a drug screening assay, diffusion of temozolomide and carmustine to hydrogel-encapsulated U87 cells from the perfusion solution is measured, and dose-response curves are generated, demonstrating utility as an in vitro mimic of the glioblastoma microenvironment.


Subject(s)
Glioblastoma , Hydrogels , Humans , Lab-On-A-Chip Devices , Temozolomide/pharmacology , Carmustine , Siloxanes , Cell Culture Techniques , Polyethylene Glycols , Tumor Microenvironment
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