Tag: pubmed

Front Biosci (Schol Ed). 2022 May 7;14(2):13. doi: 10.31083/j.fbs1402013.

ABSTRACT

The major hallmark of Parkinson’s disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra (SN), which is responsible for the core motor symptoms of PD. Currently, there is no cure for PD, and its prevalence is increasing, prompting the search for novel neuroprotective treatments. Neuroinflammation is a core pathological process in PD, evident by increased inflammatory biomarkers in the SN and cerebrospinal fluid. Interestingly, epidemiological studies have reported a reduced risk of PD in users of non-steroidal anti-inflammatory drugs compared to non-users, suggesting the neuroprotective potential of anti-inflammatory drugs. Therefore, this study aimed to: (1) test the efficacy of novel oral formulations of edaravone (EDR) and curcumin (CUR) (which possess anti-inflammatory and anti-oxidative properties) to alleviate motor and non-motor symptoms, and associated pathology in the intrastriatal lipopolysaccharide (LPS) model of PD; (2) investigate the expression of proteins linked to familial PD and markers of autophagy in the intrastriatal LPS model treated with EDR and CUR. Fifty-two C57BL/6 mice were divided into 4 groups, namely; (1) control + vehicle; (2) LPS + vehicle; (3) LPS + EDR (made in vehicle) and (4) LPS + CUR (made in vehicle). 10 μg of LPS was administered stereotaxically into the right striatum, and EDR and CUR treatments were initiated 2-weeks after the LPS injections. Behavioural tests were carried out at 4- and 8-weeks after LPS injection followed by tissue collection at 8-weeks. Intrastriatal administration of LPS induced motor deficits and anxiety-like behaviours at 4- and 8-weeks, which were accompanied by astroglial activation, increased protein expression of α-synuclein, heat shock cognate protein of 70 kDa (HSC-70) and Rab-10, and reduced levels of tyrosine hydroxylase (TH) protein in the striatum. Additionally, LPS induced astroglial activation in the olfactory bulb, along with changes in the protein expression of HSC-70. The changes associated with EDR and CUR in the striatum and olfactory bulb were not statistically significant compared to the LPS group. Intrastriatal administration of LPS induced pathological changes of PD such as motor deficits, reduced expression of TH protein and increased α-synuclein protein, as well as some alterations in proteins linked to familial PD and autophagy in the olfactory bulb and striatum, without pronounced therapeutic effects of EDR and CUR. Our results may suggest that EDR and CUR lack therapeutic effects when administered after the disease process was already initiated. Thus, our treatment regimen or the physicochemical properties of EDR and CUR could be further refined to elevate the therapeutic effects of these formulations.

PMID:35730438 | DOI:10.31083/j.fbs1402013

J Am Geriatr Soc. 2022 Jun 22. doi: 10.1111/jgs.17903. Online ahead of print.

ABSTRACT

INTRODUCTION: Prior studies on the association of glaucoma and cognitive function have reported mixed results.

METHODS: The Health and Retirement Study (HRS) is a nationally representative panel survey of Americans age ≥ 51 years. HRS-linked Medicare claims data were used to identify incident glaucoma cases (by glaucoma type). Cognitive function was measured using the Telephone Interview for Cognitive Status (TICS), administered in each wave (every 2 years). Separate linear mixed models were fitted with either prevalent or incident glaucoma as a predictor of TICS trajectories and adjusting for age, race/ethnicity, educational attainment, gender, and medical history. Negative model estimates indicate associations of glaucoma with worse cognitive function scores or steeper per-year declines in cognitive function scores.

RESULTS: Analyses of prevalent glaucoma cases included 1344 cases and 5729 controls. Analyses of incident glaucoma included 886 cases and 4385 controls. In fully-adjusted models, those with prevalent glaucoma had similar TICS scores to controls (β = 0.01; 95% Confidence Interval [CI]: -0.15, 0.18; p = 0.86). However, in those with incident glaucoma, we detected a statistically significant association between glaucoma and lower TICS scores (β = -0.29; 95% CI: -0.50, -0.08; p = 0.007). However, there was no statistically significant association between either prevalent or incident glaucoma and per-year rates of change in TICS scores. When categorizing glaucoma by type (primary open angle glaucoma, normal tension glaucoma, or other glaucoma), no significant associations were detected between either prevalent or incident glaucoma and levels of or rates of change in TICS scores in fully covariate adjusted models.

CONCLUSION: The observed associations between glaucoma and cognitive function were small and unlikely to be clinically meaningful. Compared to prior studies on this topic, this investigation provides robust evidence based on its larger sample size, longitudinal follow-up, and repeated measures of cognitive function in a population-based sample.

PMID:35730426 | DOI:10.1111/jgs.17903

AIDS. 2022 Jun 23. doi: 10.1097/QAD.0000000000003299. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the prevalence of severe transaminitis precluding tuberculosis (TB) preventive therapy (TPT) initiation for people with HIV (PWH) in a high TB/HIV burden setting.

DESIGN/METHODS: We conducted a secondary analysis of data from a prospective cohort study of PWH with pre-antiretroviral therapy (ART) CD4+ counts 350 cells/μl or less undergoing systematic TB screening from two HIV clinics in Uganda. For this analysis, we excluded patients with culture-confirmed TB and patients without aspartate transaminase (AST) or alanine transaminase (ALT) levels measured within three months of enrollment. We compared the proportion of patients with any transaminitis (AST or ALT greater than one times the upper limit of normal ULN) and severe transaminitis (AST or ALT >3 times ULN) for patients screening negative for TB by symptoms and for those screening negative by C-reactive protein (CRP). We also assessed the proportion of patients with transaminitis by self-reported alcohol consumption.

RESULTS: Among 313 participants [158 (50%) women, median age 34 years (IQR 27-40)], 75 (24%) had any transaminitis and six (2%) had severe transaminitis. Of 32 of 313 (10%) who screened negative for TB by symptoms, none had severe transaminitis. In contrast, six-times more PWH screened negative for TB by CRP (194 of 313, 62%), of whom only four (2.1%) had severe transaminitis. Differences in the proportion with any and severe transaminitis according to alcohol consumption were not statistically significant.

CONCLUSION: Prevalence of severe transaminitis was low among PWH without culture-confirmed TB in this setting, and is therefore, unlikely to be a major barrier to scaling-up TPT.

PMID:35730395 | DOI:10.1097/QAD.0000000000003299

AIDS. 2022 Jun 23. doi: 10.1097/QAD.0000000000003282. Online ahead of print.

ABSTRACT

We performed a calendar-matched, 12-month, before (November 27, 2017 to November 26, 2018) and after (November 27, 2018 to November 26, 2019) study, to assess the utility of an ED-based HIV screening program. There were 710 and 14,335 patients screened for HIV during the pre- and post-BPA periods, respectively, representing more than a 20-fold increase in HIV screening following BPA implementation. Total HIV positive tests increased 5-fold following BPA implementation.

PMID:35730396 | DOI:10.1097/QAD.0000000000003282

Acta Psychiatr Scand. 2022 Jun 22. doi: 10.1111/acps.13463. Online ahead of print.

ABSTRACT

OBJECTIVE: In Denmark, data on hospital contacts are reported to the Danish National Patient Registry (DNPR). The ICD-10 main diagnoses from the DNPR are often used as proxies for mental disorders in psychiatric research. With the transition from the second version of the DNPR (DNPR2) to the third (DNPR3) in February-March 2019, the way main diagnoses are coded in relation to outpatient treatment changed substantially. Specifically, in the DNPR2, each outpatient treatment course was labelled with only one main diagnosis. In the DNPR3, however, each visit during an outpatient treatment course is labelled with a main diagnosis. We assessed whether this change led to a break in the diagnostic time-series represented by the DNPR, which would pose a threat to the research relying on this source.

METHODS: All main diagnoses from outpatients attending the Psychiatric Services of the Central Denmark Region from 2013 to 2021 (n=100,501 unique patients) were included in the analyses. The stability of the DNPR diagnostic time-series at the ICD-10 subchapter level was examined by comparing means across the transition from the DNPR2 to the DNPR3.

RESULTS: While the proportion of psychiatric outpatients with diagnoses from some ICD-10 subchapters changed statistically significantly from the DNPR2 to the DNPR3, the changes were small in absolute terms (e.g., +0.6% for F2 – psychotic disorders and +0.6% for F3 – mood disorders).

CONCLUSION: The change from the DNPR2 to the DNPR3 is unlikely to pose a substantial threat to the validity of most psychiatric research at the diagnostic subchapter level.

PMID:35730386 | DOI:10.1111/acps.13463

AIDS. 2022 Jun 23. doi: 10.1097/QAD.0000000000003292. Online ahead of print.

ABSTRACT

BACKGROUND: Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.

METHODS: A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women’s Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).

RESULTS: At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17 vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8 vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy (P = 0.69) and HIV status (P = 0.53) were not.

CONCLUSION: Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes.

PMID:35730385 | DOI:10.1097/QAD.0000000000003292

AIDS. 2022 Jun 23. doi: 10.1097/QAD.0000000000003290. Online ahead of print.

ABSTRACT

OBJECTIVE: Given the roll out of maternal antiretroviral therapy (ART) for prevention-of-perinatal-HIV-transmission, increasing numbers of children are perinatally HIV/ART exposed but uninfected (CAHEU). Some studies suggest CAHEU may be at increased risk for neurodevelopmental (ND) deficits. We aimed to assess ND performance among preschool CAHEU.

DESIGN: This cross-sectional study assessed ND outcomes among 3-6-year-old CAHEU at entry into a multicountry cohort study.

METHODS: We used the Mullen Scales of Early Learning (MSEL) and Kaufman Assessment Battery for Children (KABC-II) to assess ND status among 3-6-year-old CAHEU at entry into the PROMISE Ongoing Treatment Evaluation (PROMOTE) study conducted in Uganda, Malawi, Zimbabwe and South Africa. Statistical analyses (Stata 16.1) was used to generate group means for ND composite scores and subscale scores, compared to standardized test score means. We used multivariable analysis to adjust for known developmental risk factors including maternal clinical/socioeconomic variables, child sex, growth-for-age measurements, and country.

RESULTS: 1647 children aged 3-6 years had baseline ND testing in PROMOTE; group-mean unadjusted Cognitive Composite scores on the MSEL were 85.8 (standard deviation [SD]: 18.2) and KABC-II were 79.5 (SD: 13.2). Composite score group-mean differences were noted by country, with South African and Zimbabwean children having higher scores. In KABC-II multivariable analyses, maternal age >40 years, lower education, male sex, and stunting were associated with lower composite scores.

CONCLUSIONS: Among a large cohort of 3-6 year old CAHEU from eastern/southern Africa, group-mean composite ND scores averaged within the low-normal range; with differences noted by country, maternal clinical and socioeconomic factors.

PMID:35730383 | DOI:10.1097/QAD.0000000000003290

Zygote. 2022 Jun 22:1-7. doi: 10.1017/S0967199422000193. Online ahead of print.

ABSTRACT

This study aimed to evaluate the effect of the cryopreservation duration (up to 160 months) on the clinical and neonatal outcomes of slow-frozen early-cleavage human embryos. Clinical data collected between February 2013 and August 2017 were included in this retrospective study. Cases were classified into five groups by the duration of cryopreservation: Group 1, 6-12 months; Group 2, 13-36 months; Group 3, 37-60 months; Group 4, 61-84 months; and Group 5, >84 months. The embryo survival rate, implantation rate, clinical pregnancy rate, live-birth rate, newborn sex ratio, singleton gestational age, singleton birth weight and malformation rate were compared between the groups. The cryopreservation duration did not significantly affect the rates of clinical pregnancy (P = 0.119) and live birth (P = 0.354), the newborn sex ratio (P = 0.614) or the singleton gestational age (P = 0.212) and birthweight (P = 0.212). Although decreases in the embryo survival and implantation rates were observed in groups 4 and 5 compared with those in groups 1-3, these differences were not statistically significant (P = 0.329, P = 0.279, respectively). Long-term cryopreservation does not appear to adversely affect the clinical and neonatal outcomes of slow-frozen early-cleavage human embryos.

PMID:35730368 | DOI:10.1017/S0967199422000193

J Periodontal Res. 2022 Jun 22. doi: 10.1111/jre.13025. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic progressive inflammation that invades periodontal supporting tissues, in which periodontal tissue regeneration engineering offers new hope for prevention and treatment, including seed cells, scaffolds, and growth factors. In recent years, scholars have shown that autologous teeth can be used as new bone tissue repair materials for periodontal regeneration and bone tissue repair. The aim of this study was to establish a human periodontal ligament cell line that expresses the human bone morphogenetic protein 2 gene (BMP2) in a stable manner using lentiviral mediation in order to explore the effect of BMP2 from autologous tooth on the proliferative and osteogenic capacity of human periodontal ligament cells (hPDLCs).

MATERIALS AND METHODS: Human periodontal ligament cells were cultured, subcultured, and identified, and then homologous recombinant lentivirus plasmid plv-BMP2 was constructed and transfected into the third passage (P₃ ) hPDLCs. After that, the effect of BMP2 on its proliferation was detected by CCK-8, at the same time, the osteogenic induction of hPDLCs was carried out at 7, 14, and 21 days, and then the effect of BMP2 on its osteogenic ability was detected by alizarin red staining, alkaline phosphatase activity determination, and the mRNA expression levels of osteogenic-related genes using real-time fluorescence quantitative PCR, including alkaline phosphatase, runt-related transcription factor 2, bone sialoprotein, osteocalcin, osteopontin, and collagen I. Finally, spss26.0 software was used for statistical processing.

RESULTS: The results showed that cells transfected with the homologous recombinant lentiviral plasmid pLV-BMP2 had a similar morphology to normal hPDLCs, showing a typical radial arrangement; the cell proliferative capacity of the pLV-BMP2 group as measured by CCK-8 was enhanced compared with the control group and the pLV-puro group (p < .05); alizarin red staining and alkaline phosphatase activity assay showed that the osteogenic ability of pLV-BMP2 was significantly enhanced compared with the control and pLV-puro groups (p < .01), and the findings of real-time fluorescence-based quantitative PCR showed high expression of osteogenic-related genes in pLV-BMP2 group (p < .01).

CONCLUSION: In conclusion, a stable periodontal ligament cell line overexpressing BMP2 was successfully established by a lentivirus-mediated method, which proved that BMP2 has a strong ability to promote the proliferation and osteogenesis of hPDLCs, thereby providing an opportunity for the study of periodontal tissue regeneration as well as providing an experimental basis for the application of autologous teeth as a new type of bone repair material for periodontal therapy and even for maxillofacial bone tissue repair.

PMID:35730345 | DOI:10.1111/jre.13025

Ther Apher Dial. 2022 Jun 22. doi: 10.1111/1744-9987.13900. Online ahead of print.

ABSTRACT

INTRODUCTION: Plasmapheresis is a frequently used procedure that removes the pathogenic components from circulation. We aimed to evaluate the relationship between plasmapheresis, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and mortality in the intensive care unit (ICU) between 2014 and 2021.

METHODS: 49 patients (27 females and 22 males) were included. Demographic characteristics, laboratory values of the day of admittance to the ICU, APACHE II scores, and length of stay were recorded.

RESULTS: The mean age was 52.73±16.93. APACHE II value (p=0.003; p<0.01), NLR ratio (p=0.001; p<0.01) and PLR ratio (p=0.001; p<0.01) of the surviving group were lower than those of the deceased group, which was statistically significant.

CONCLUSION: As high PLR and NLR levels suggest increased mortality in the ICU population, attention should be paid for increased NLR and PLR when plasmapheresis is decided on in the ICU.

PMID:35730341 | DOI:10.1111/1744-9987.13900