The early-life microbiome appears to be affected by mode of delivery, but this effect may depend on intrapartum antibiotic exposure. Here, we assess the effect of delivery mode on gut microbiota, ...independent of intrapartum antibiotics, by postponing routine antibiotic administration to mothers until after cord clamping in 74 vaginally delivered and 46 caesarean section born infants. The microbiota differs between caesarean section born and vaginally delivered infants over the first year of life, showing enrichment of Bifidobacterium spp., and reduction of Enterococcus and Klebsiella spp. in vaginally delivered infants. The microbiota composition at one week of life is associated with the number of respiratory infections over the first year. The taxa driving this association are more abundant in caesarean section born children, providing a possible link between mode of delivery and susceptibility to infectious outcomes.
BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study ...involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 95% confidence interval, +0.03 to +1.68). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β standard error, −1.19 0.43 and −0.68 0.33 log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 95% confidence interval, 0.03–0.35 and 0.30 0.10–0.90 for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001) ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance
Background
There is increasing use of anti‐osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse ...reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)‐SCAR.
Objective
To characterize patients with AOA‐SCAR and investigate the HLA association and utility of in vitro diagnostic methods.
Methods
We enrolled 16 cases with AOA‐cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens–Johnson syndrome SJS and 2 with drug rash with eosinophilia and systemic symptoms DRESS) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA‐SCAR, and tolerability to alternative drugs. We further performed literature review and meta‐analysis on the HLA association of AOA‐SCAR.
Results
Our data showed strontium ranelate is the most common causality of AOA‐SCAR in Asian populations. There was no cross‐hypersensitivity of SR‐SCAR with other AOA. HLA genotyping showed that SR‐SJS was most significantly associated with HLA‐A*33:03 (Pc = 5.17 × 10−3, OR: 25.97, 95% CI: 3.08–219.33). Meta‐analysis showed that HLA‐A*33:03 was associated with SR‐SJS (P = 5.01 × 10−5; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR‐SJS was 83.3%.
Conclusions
Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA‐A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR‐SCAR in patients whose reaction developed while taking multiple drugs.
Linked Commentary: T. Shiohara. J Eur Acad Dermatol Venereol 2021; 35: 567‐568. https://doi.org/10.1111/jdv.17138.
Summary The goal of this study was to document how treatment with high doses of zoledronic acid affects dental extraction healing. Our results, showing significantly compromised osseous healing ...within the socket as well as presence of exposed bone and development of a sequestrum in one animal, provide a building block toward understanding osteonecrosis of the jaw. Purpose The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction. Methods Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the fourth premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using microcomputed tomography (micro-CT) and dynamic histomorphometry. Results The initial infilling of the extraction socket with bone was not affected by ZOL, but subsequent removal of this bone was significantly suppressed compared to CON. After 8 weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of ∼50% per year in CON animals while ZOL-treated animals had a rate of <1% per year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw. Conclusions These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw.
Objective:Studies have shown that Housing First, a recovery-oriented housing intervention, is effective in reducing service utilization among homeless individuals with mental illness, but less is ...known about how Housing First affects patterns of service use over time and about characteristics associated with various utilization trajectories. This analysis aimed to explore latent class trajectories of shelter utilization in a randomized controlled trial of Housing First conducted across five Canadian cities.Methods:Data from the At Home/Chez Soi trial were analyzed (N=2,058). Latent class growth analysis was performed using days of shelter utilization to identify trajectories over 24 months. Multinomial logistic regression was used to determine which baseline variables, including treatment group, could predict class membership.Results:Four shelter use trajectories were identified: consistently low (N=1,631, 79%); mostly low (N=120, 6%); early temporary increase (N=179, 9%); and higher use, late temporary increase (N=128, 6%). Treatment group was a significant predictor of class membership. Those enrolled in Housing First had lower odds of experiencing higher shelter use trajectories (mostly low: odds ratio OR=0.50, 95% confidence interval CI=0.34–0.72; early temporary increase: OR=0.21, 95% CI=0.15–0.31; higher use, late temporary increase: OR=0.14, 95% CI=0.09–0.22). Other variables associated with trajectory classes included older age and longer time homeless, both of which were associated with higher shelter use.Conclusions:Several participant characteristics were associated with different shelter use patterns. Knowledge of variables associated with more favorable trajectories may help to inform service planning and contribute to modeling efforts for homelessness.
Air pollution has become an alarming issue in Vietnam recently; however, there was only one study so far on the effects of ambient air pollution on population health. Our study aimed to investigate ...the short-term effects of air pollutants including PM10, NO2, SO2, and O3 on respiratory and cardiovascular hospitalizations in Ho Chi Minh City (HCMC), the largest city in Vietnam. Data on hospitalization from the two largest hospitals in HCMC and daily records of PM10, NO2, SO2, O3 and meteorological data were collected from February 2004 to December 2007. A time-series regression analysis with distributed lag model was applied for data analysis. Changes in levels of NO2 and PM10 were strongly associated with hospital admissions for both respiratory and cardiovascular diseases (CVD); whereas levels of SO2 were only moderately associated with respiratory and CVD hospital admissions and O3 concentration was not associated with any of them. For a 10μg/m3 increase of each air pollutant, the risk of respiratory admissions increased from 0.7% to 8% while the risk of CVD admissions increased from 0.5% to 4%. Females were found to be more sensitive than males to exposure to air pollutants in regard to respiratory diseases. In regard to CVD, females (RR, 1.04, 95% CI, 1.01–1.07) had a slightly higher risk of admissions than males (RR, 1.03, 95% CI, 1–1.06) to exposure to NO2. In contrast, males (RR, 1.007, 95%CI, 1–1.01) had a higher risk of admission than females (RR, 1.004, 95%CI, 1.001–1.007) to exposure to PM10. People in the age group of 5–65year-olds had a slightly higher risk of admissions caused by air pollutants than the elderly (65+years old) except for a significant effect of PM10 on the risk of cardiovascular admissions was found for the elderly only.
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•Ho Chi Minh City, Vietnam was vulnerable to high level of air pollution.•NO2 and PM10 were significantly associated with cardiorespiratory hospitalizations.•SO2 and O3 had inconsistent effects on cardiorespiratory hospitalizations.•Elderly people were more sensitive to cardiovascular risk of air pollution than others.•A prevention program that reduces health risk caused by air pollution is recommended.
Abstract
STUDY QUESTION
Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized ...processing/freezing for centers that do not have those capabilities?
SUMMARY ANSWER
Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice.
WHAT IS KNOWN ALREADY
Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring.
STUDY DESIGN, SIZE, DURATION
Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient’s tissue was donated to research and 75% was stored for patient’s future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1.
MAIN RESULTS AND THE ROLE OF CHANCE
The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg—6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132.
LIMITATIONS, REASONS FOR CAUTION
This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size.
WIDER IMPLICATIONS OF THE FINDINGS
Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested.
STUDY FUNDING/COMPETING INTEREST(S)
Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.
Diabetes mellitus is characterized by chronic hyperglycemia and its diverse complications. Hyperglycemia is associated with inflammatory responses in different organs and diabetic patients have a ...higher risk of developing neurodegenerative disorders. Methylglyoxal is a reactive advanced glycation end product precursor that accumulates in diabetic patients. It induces various stress responses in the central nervous system and causes neuronal dysfunction. Astrocytes are actively involved in maintaining neuronal homeostasis and possibly play a role in protecting the brain against neurodegeneration. However it is not clear whether methylglyoxal exerts any adverse effects towards these astrocytes. In the present study we investigated the effects of methylglyoxal in astrocytic cultures and hippocampi of experimental animals. The cells from the astrocytic line DITNC1 were treated with methylglyoxal for 1 to 24 h. For the in vivo model, 3 months old C57BL/6 mice were treated with methylglyoxal solution for 6 weeks by intraperitoneal injection. Following the treatment, both astrocytes and hippocampi were harvested for MTT assay, Western blot and real time PCR analyses. We found that methylglyoxal induced astrogliosis in DITNC1 astrocytic cultures and C57BL/6 mice. Further, activation of the pro-inflammatory JNK signaling pathway and its downstream effectors c-Jun were observed. Furthermore, increased gene expression of pro-inflammatory cytokines and astrocytic markers were observed from real time PCR analyses. In addition, inhibition of JNK activities resulted in down-regulation of TNF-α gene expression in methylglyoxal treated astrocytes. Our results suggest that methylglyoxal may contribute to the progression of diabetes related neurodegeneration through JNK pathway activation in astrocytes and the subsequent neuroinflammatory responses in the central nervous system.
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