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The Journal of Allergy and Clinical... Jun 2024Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses.
BACKGROUND
Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses.
OBJECTIVE
To investigate the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD).
METHODS
The study included a phase I open-label trial followed by a phase II randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD.
RESULTS
In phase I, intravenous (IV) administration of hcMSCs at two doses (1×10 and 5×10 cells/kg) was safe and well-tolerated in 20 subjects. Since there was no difference between the two dosage groups (P=0.9), it was decided to administer low-dose hcMSCs only for phase II. In phase II, subjects receiving three weekly IV infusions of hcMSCs at 5x10 cells/kg showed a higher proportion of an eczema area and severity index (EASI)-50 response at week 12 compared to the placebo group (P=0.038). The differences between groups in the dermatology life quality index and pruritus numerical-rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period.
CONCLUSIONS
Our findings demonstrate that hcMSCs treatment resulted in a significantly higher rate of achieving EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSCs treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.
PubMed: 38944393
DOI: 10.1016/j.jaci.2024.06.013 -
Journal of Infection and Chemotherapy :... Jun 2024Some reports suggest that coronavirus disease 2019 (COVID-19) may affect male reproductive function. There is also concern in Japan that COVID-19 may contribute to the...
Some reports suggest that coronavirus disease 2019 (COVID-19) may affect male reproductive function. There is also concern in Japan that COVID-19 may contribute to the pre-existing decline in male fertility; however, no studies have investigated the effects of COVID-19 on male reproductive function. In this study, we aimed to analyze the semen quality of men who had recovered from COVID-19. Male patients who had recovered from COVID-19 between February 2020 and September 2021 were recruited for this study. Participants were sent a semen collection kit; they were asked to collect semen at home and deliver it to a laboratory at Osaka University. We used these samples to analyze sperm concentration, total sperm count, and semen volume. In total, 125 participants were included in this study. The median age of all patients was 46 years (interquartile range (IQR): 38-52 years). The severity of COVID-19 was mild in 80 patients; 19 were moderate I, 22 were moderate II, and four were severe. The median semen volume was 2.5 mL (IQR: 1.8-3.1), the median sperm concentration was 98.9 million/mL (IQR: 43.8-162.2), and the median total sperm count was 212.1 million (IQR: 89.7-368.2). In a previous study in Japan, the median sperm count in adult men was reported to be 201 million. Participants in our study did not have lower sperm counts than this, despite their older age. Our results suggest that the long-term effects of COVID-19 on spermatogenesis are minimal.
PubMed: 38944382
DOI: 10.1016/j.jiac.2024.06.021 -
Journal of Shoulder and Elbow Surgery Jun 2024The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty...
Medial Scapular Body (MSB) Goutallier Classification - MRI based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.
INTRODUCTION
The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal MRI sections at medial scapular body, the Medial Scapular Body - Goutallier Classification (MSB-GC) will improve reliability and repeatability giving a more representative approximation to the degree of fatty infiltration, as compared with original Y-view.
METHODS
Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0 to 4) at three defined sections section 1: original Y-view; section 2: level of suprascapular notch; section 3: three cm medial to suprascapular notch on MRI scans. Six sub-specialist fellowship trained shoulder surgeons, and three musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients.
RESULTS
Out of 80 scans, 78% (n=62) were massive cuff tears involving supraspinatus, infraspinatus and subscapularis tendon. Inter-observer reliability (consistency between observers) for Goutallier grade was excellent for all three predefined sections (range:0.87-0.95). Intra-observer reliability (repeatability) for Goutallier grade was excellent for all three sections and four rotator cuff muscles (range:0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (p<0.001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles. 42.5% of both supraspinatus and infraspinatus were downgraded by one, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2 and 2.5% of supraspinatus were downgraded by 3.
CONCLUSION
This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision-making which should be studied further in clinical studies.
PubMed: 38944373
DOI: 10.1016/j.jse.2024.05.013 -
Journal of Minimally Invasive Gynecology Jun 2024To evaluate the effectiveness of using vascular clips to seal targeted lymphatics in gynecological malignancies for the prevention of postoperative pelvic lymphocele and...
STUDY OBJECTIVE
To evaluate the effectiveness of using vascular clips to seal targeted lymphatics in gynecological malignancies for the prevention of postoperative pelvic lymphocele and symptomatic lymphocele after laparoscopic pelvic lymphadenectomy.
DESIGN
Retrospective analysis.
SETTING
Single-center academic hospital.
PATIENTS
In total, 217 patients with gynecological malignancies were included.
INTERVENTIONS
Patients were classified into two groups: group 1 (vascular clips were used to seal the targeted lymphatics) and group 2 (electrothermal instruments were used to seal the targeted lymphatics). The patients were followed up 4-6 weeks after surgery to evaluate the incidence of lymphoceles by ultrasound or CT. Symptomatic lymphoceles are defined as those that cause infection, deep vein thrombosis with or without swelling of the extremities, edema (swelling) of the extremities or perineum, hydronephrosis and/or moderate to severe pain.
MEASUREMENT AND MAIN RESULTS
One hundred and thirteen patients were enrolled in group 1, and 104 patients were enrolled in group 2. Lymphoceles were observed in 46 (21.2%) patients. Fewer lymphoceles occurred in group 1 than in group 2 [8 (7.1%) vs. 38 (36.5%), p < 0.001]. The percentage of significantly sized lymphoceles was lower in group 1 than that in group 2 [4 (3.5%) vs. 30 (28.8%), p < 0.001]. Symptomatic lymphoceles occurred in 18 patients (8.3%), and only one (1.0%) occurred in group 1, while 17 (16.3%) occurred in group 2 (p < 0.001). A multivariate analysis revealed that vascular clips were the only independent factor for preventing lymphocele (OR = 7.65, 95% CI = [3.30, 17.13], p < 0.001) and symptomatic lymphocele (OR = 22.03, 95% CI = [2.84, 170.63], p = 0.003).
CONCLUSIONS
The results indicate that the use of vascular clips may be useful for the prevention of the development of lymphocele and symptomatic lymphocele secondary to pelvic lymphadenectomy performed via laparoscopy.
PubMed: 38944337
DOI: 10.1016/j.jmig.2024.06.011 -
The Science of the Total Environment Jun 2024Enhancing the agroecosystems carbon (C) sink function for climate mitigation faced challenges, particularly with traditional measures with limited suitability for...
Enhancing the agroecosystems carbon (C) sink function for climate mitigation faced challenges, particularly with traditional measures with limited suitability for increasing soil organic carbon (SOC) stocks. Inducing a SOC undersaturation in the topsoil by abrupt subsoil admixture is a way to create an additional C sink. However, the deep tillage traditionally used for this topsoil dilution was not always successful. It was due to a lack of knowledge and suitable approaches to record the effect of all relevant factors in SOC recovery, including soil conditions and fertilizer forms. We addressed these problems by establishing a three-factorial experiment: I) "moderate topsoil dilution," II) "N fertilization form," and III) "soil erosion state," representing three soil types in the hummocky ground moraine landscape of NE Germany. SOC dynamics were determined over a year of winter rye cropping using a novel robotic chamber system capable of measuring CO exchange on 36 experimental plots with a reduced methodological bias than previous measuring systems. The averaged net ecosystem carbon balance, a proxy for SOC stock change, indicated that topsoil dilution only reduced further SOC losses. The N fertilizer form had a significantly stronger and more differentiated effect. While the mineral N fertilization consistently produced only C sources, the organic fertilization, in combination with the diluted topsoil, led to a C sink. This C-sink function was, however, more pronounced in the eroded soil than in the non-eroded soil. Overall, the results have made clear that the impact of topsoil dilution on the further development of the SOC stock is only possible if the effect of other relevant factors, such as N fertilizer form and erosion state, are taken into account.
PubMed: 38944309
DOI: 10.1016/j.scitotenv.2024.174243 -
Bone Jun 2024Recent research has revealed several important pathways of epigenetic regulation leading to transcriptional changes in bone cells. Rest Corepressor 2 (Rcor2) is a...
Recent research has revealed several important pathways of epigenetic regulation leading to transcriptional changes in bone cells. Rest Corepressor 2 (Rcor2) is a coregulator of Lysine-specific histone demethylase 1 (Lsd1), a demethylase linked to osteoblast activity, hematopoietic stem cell differentiation and malignancy of different neoplasms. However, the role of Rcor2 in osteoblast differentiation has not yet been examined in detail. We have previously shown that Rcor2 is highly expressed in mesenchymal stromal cells (MSC) and particularly in the osteoblastic lineage. The role of Rcor2 in osteoblastic differentiation in vitro was further characterized and we demonstrate here that lentiviral silencing of Rcor2 in MC3T3-E1 cells led to a decrease in osteoblast differentiation. This was indicated by decreased alkaline phosphatase and von Kossa stainings as well as by decreased expression of several osteoblast-related marker genes. RNA-sequencing of the Rcor2-downregulated MC3T3-E1 cells showed decreased repression of Rcor2 target genes, as well as significant upregulation of majority of the differentially expressed genes. While the heterozygous, global loss of Rcor2 in vivo did not lead to a detectable bone phenotype, conditional deletion of Rcor2 in limb-bud mesenchymal cells led to a moderate decrease in cortical bone volume. These findings were not accentuated by challenging bone formation by ovariectomy or tibial fracture. Furthermore, a global deletion of Rcor2 led to decreased white adipose tissue in vivo and decreased the capacity of primary cells to differentiate into adipocytes in vitro. The conditional deletion of Rcor2 led to decreased adiposity in fracture callus. Taken together, these results suggest that epigenetic regulation of mesenchymal stromal cell differentiation is mediated by Rcor2, which could thus play an important role in defining the MSC fate.
PubMed: 38944098
DOI: 10.1016/j.bone.2024.117180 -
The Lancet. Oncology Jun 2024There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for...
BACKGROUND
There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.
METHODS
The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.
FINDINGS
Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.
INTERPRETATION
Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.
FUNDING
Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.
PubMed: 38944050
DOI: 10.1016/S1470-2045(24)00269-9 -
The Journal of Nutrition, Health & Aging Jun 2024Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study...
OBJECTIVES
Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs.
METHODS
A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC.
RESULTS
Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]).
CONCLUSIONS
Intervention for improving medication non-adherence among older adults with NCDs should consider IC.
PubMed: 38943981
DOI: 10.1016/j.jnha.2024.100303 -
The International Journal on Drug Policy Jun 2024Alcohol pricing policies may reduce alcohol-related harms, yet little work has been done to model their effectiveness beyond health outcomes especially in Australia. We...
AIMS
Alcohol pricing policies may reduce alcohol-related harms, yet little work has been done to model their effectiveness beyond health outcomes especially in Australia. We aim to estimate the impacts of four taxation and minimum unit pricing (MUP) interventions on selected social harms across sex and age subgroups in Australia.
METHODS
We used econometrics and epidemiologic simulations using demand elasticity and risk measures. We modelled four policies including (A) uniform excise rates (UER) (based on alcohol units) (B) MUP $1.30 on all alcoholic beverages (C) UER + 10 % (D) MUP$ 1.50. People who consumed alcohol were classified as (a) moderate (≤ 14 Australian standard drinks (SDs) per week) (b) Hazardous (15-42 SDs per week for men and 14-35 ASDs for women) and (c) Harmful (> 42 SDs per week for men and > 35 ASDs for women). Outcomes were sickness absence, sickness presenteeism, unemployment, antisocial behaviours, and police-reported crimes. We used relative risk functions from meta-analysis, cohort study, cross-sectional survey, or attributable fractions from routine criminal records. We applied the potential impact fraction to estimate the reduction in social harms by age group and sex after implementation of pricing policies.
RESULTS
All four modelled pricing policies resulted in a decrease in the overall mean baseline of current alcohol consumption, primarily due to fewer people drinking harmful amounts. These policies also reduced the total number of crimes and workplace harms compared to the current taxation system. These reductions were consistent across all age and sex subgroups. Specifically, sickness absence decreased by 0.2-0.4 %, alcohol-related sickness presenteeism by 7-9 %, unemployment by 0.5-0.7 %, alcohol-related antisocial behaviours by 7.3-11.1 %, and crimes by 4-6 %. Of all the policies, the implementation of a $1.50 MUP resulted in the largest reductions across most outcome measures.
CONCLUSION
Our results highlight that alcohol pricing policies can address the burden of social harms in Australia. However, pricing policies should just form part of a comprehensive alcohol policy approach along with other proven policy measures such as bans on aggressive marketing of alcoholic products and enforcing the restrictions on the availability of alcohol through outlet density regulation or reduced hours of sale to have a more impact on social harms.
PubMed: 38943908
DOI: 10.1016/j.drugpo.2024.104502 -
Comprehensive Psychiatry Jun 2024Several studies have explored the relationship between personality and work addiction, suggesting that individuals with certain mental disorders, including personality...
BACKGROUND
Several studies have explored the relationship between personality and work addiction, suggesting that individuals with certain mental disorders, including personality disorders such as obsessive-compulsive personality disorder (OCPD), may be more prone to work addiction. However, the characterization of personality organization (PO) among workaholics and its contribution to the persistence of work addiction remains unclear.
METHODS
In this longitudinal study of a representative sample of young adults (N = 1748), we applied the Bergen Work Addiction Scale and the Inventory of Personality Organization.
RESULTS
We found significant correlations between work addiction and identity diffusion, primitive psychological defenses, reality testing, and overall personality disorganization across three waves. A latent class growth analysis revealed three profiles: no work addiction, increasing work addiction, and constant moderate work addiction. Multinomial logistic regression analysis indicated that higher levels of personality disorganization in wave 1 and increases in personality disorganization between waves 1 and 3 were associated with higher odds of belonging to the increasing work addiction group. Similarly, higher overall personality disorganization in wave 1 was associated with higher odds of belonging to the constant moderate work addiction group.
CONCLUSION
These findings suggest that individuals with chronic work addiction have lower levels of PO, and PO declines as work addiction persists. Screenings for work addiction are recommended to prevent potential mental health issues. Future research should explore the influence of workplace characteristics and work motivations on the association between work addiction and personality disorders.
PubMed: 38943714
DOI: 10.1016/j.comppsych.2024.152513