Sunday, July 24, 2022

Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia‐Pacific

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Abstract

Introduction:

Liver disease is a growing burden among PLHIV in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD).

Methods:

Patients on cART with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels >5 times its upper limit of normal) were analysed using repeated measure logistic regression over a ten-year follow-up period. Liver cirrhosis was defined as having an APRI score >1.5, FIB-4 score >3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyse factors associated with cirrhosis among those in follow-up after 2015.

Results:

Of 5182 patients, 101 patients (1.9%) had high ALT levels with HCV-antibody positive (OR 4.98, 95%CI 2.82-8.77, p <0.001) an d ever high alcohol consumption (OR 2.33, 95% CI 1.00-5.46, p=0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate= 0.82 per 100 person-years). Those HCV-antibody positive (HR 5.54, 95% CI 3.75-8.18, p<0.001) and had high alcohol consumption (HR 2.06, 95%CI 1.23-3.45, p=0.006) were associated with liver cirrhosis.

Conclusion:

HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reduce the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

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Interferon‐gamma inducible protein 16 and type I interferon receptors expression in experimental apical periodontitis induced in wild type mice

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Abstract

Aim

The aim of this study was to evaluate the IFI16 and IFN-α/β receptors expression during the genesis and development of experimental apical periodontitis (AP) in mice teeth.

Methodology

AP was induced in the lower first molars of 40 C57BL/6 mice. They were divided according to the experimental periods 2, 7, 14, 21 and 42 days (n=8 per group). Five animals were used as a control group (without AP). Specimens were submitted to histological processing for description of the inflammatory process, immunostaining for the presence/absence and localization of IFI16 and IFN-α/β receptors (qualitative and semi-quantitative analysis), and tartrate-resistant acid phosphatase (TRAP) histoenzimology.

Results

The results showed a gradual development of AP over the experimental times. The expression of IFI16 was noticeably more exacerbated in the experimental early period (day 2) while the lowest expression was observed in the control group (p=0.02). For IFN-α/β receptors, a higher intensity staining was observed 42 days after AP induction, that was statistically different from the control group (p=0.02). Also, the number of TRAP positive cells was higher on the later periods (days 21 and 42) (p<0.001).

Conclusion

IFI16 protein expression was highest during the early periods after apical periodontitis induction in mice teeth, whilst IFN-α/β receptors expression was highest after apical periodontitis became established.

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Protective Effects of Cannabis sativa on chemotherapy‐induced nausea

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Abstract

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa (C. sativa) and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (8 animals per group): Group 1: Normal control (saline i.p). Group 2: rats received cyclophosphamide (200 mg/kg i.p) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg ip) across days 1 – 7 and C. sativa (20 and 40 mg/kg sc) was administered on cyclophosphamide days 4 – 7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestina l homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5HT, dopamine and noradrenaline, as well as, decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa, also, improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.

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Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

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Abstract

Background

Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified.

Methods

We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic SCT recipients. Patients who underwent SCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control.

Results

The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs 71.6%, P < 0.05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs 19.8%, P < 0.05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (HR = 2.76, 95% confidence interval 1.14 – 6.68, P < 0.05).

Conclusion

Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis.

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Thursday, July 21, 2022

Oral microbiome diversity – The curious case of Corynebacterium sp. isolation

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Abstract

Oral microbiome sequencing efforts revealed the presence of hundreds of different microbes. Interindividual differences at strain and species resolution suggests that microbiome diversity could lead to mechanistically distinct gene regulation as well as species related differences in phenotypes. Commonly, gene regulation and related phenotypes are studied in a few selected strains of a particular species with conclusions that are mostly generalized. The aim of this study was to isolate several species of Corynebacterium using an established protocol that led to the previous isolation of C. durum. Characterization of C. durum interspecies interactions revealed a specific mechanism for chain elongation in Streptococcus sanguinis that was the result of corynebacterial fatty acid production and secretion. While the protocol was successful applied to isolate what we presumed to be additional Corynebacterium based on several phenotypic traits that seem to be identical to C. durum, genome sequencing of the newly isolated strains placed them closer to Actinomyces. Both Corynebacterium and Actinomyces are sub-orders of the Actino-bacteridae and related species. Our study suggests to take several comprehensive strategies into consideration when taxonomically identifying closely related microorganisms. Furthermore, it seems to be important to test common core phenotypes in bacterial ecology to understand the behavior of specific groups of microbes, rather than simply relying upon genome sequence homology to establish relationships in the microbiome.

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Associations of Prior Head Injury With Olfaction in Older Adults

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This cohort study investigates the associations of prior head injury, number of prior head injuries, and head injury severity with subjective and psychophysical olfactory function in older adults.
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Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial

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Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increas...
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ELF4 is a critical component of a miRNA-transcription factor network and is a bridge regulator of glioblastoma receptor signaling and lipid dynamics

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Abstract
Background
The loss of neurogenic tumor suppressor microRNAs miR-124, miR-128, and miR-137 is associated with glioblastoma's undifferentiated state. Most of their impact comes via the repression of a network of oncogenic transcription factors. We conducted a high-throughput functional siRNA screen in glioblastoma cells and identify E74 like ETS transcription factor 4 (ELF4) as the leading contributor to oncogenic phenotypes.
Methods
In vitro and in vivo assays were used to assess ELF4 impact on cancer phenotypes. We characterized ELF4's mechanism of action via genomic and lipidomic analyses. A MAPK reporter assay verified ELF4's impact on MAPK signaling, and qRT-PCR and western blotting were used to corroborate ELF4 regulatory role on most relevant target genes.
Results
ELF4 knockdown resulted in significant proliferation delay and ap optosis in GBM cells and long-term growth delay and morphological changes in glioma stem cells (GSCs). Transcriptomic analyses revealed that ELF4 controls two interlinked pathways: 1) Receptor tyrosine kinase signaling, and 2) Lipid dynamics. ELF4 modulation directly affected Receptor Tyrosine Kinase (RTK) signaling, as mitogen-activated protein kinase (MAPK) activity was dependent upon ELF4 levels. Furthermore, shotgun lipidomics revealed that ELF4 depletion disrupted several phospholipid classes, highlighting ELF4's importance in lipid homeostasis.
Conclusions
We found that ELF4 is critical for the GBM cell identity by controlling genes of two dependent pathways: RTK signaling (SRC, PTK2B, TNK2) and lipid dynamics (LRP1, APOE, ABCA7, PLA2G6, and PITPNM2). Our data suggests that targeting these two pathways simultaneously may be therapeutically beneficial to GBM patients.
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Evaluation of facial soft tissue asymmetric changes in Class III patients after orthognathic surgery using three-dimensional stereophotogrammetry

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The aim of this study was to investigate changes in facial soft tissue asymmetry over time after orthognathic surgery in Class III patients using three-dimensional stereophotogrammetry. The study included 101 patients with a skeletal Class III malocclusion (72 female, 29 male; age range 19 –53 years, mean age 28.6 years) who underwent orthognathic surgery. The minimum follow-up was 12 months. Three-dimensional photographs were acquired using the 3dMDtrio stereophotogrammetry system, and 21 anthropometric landmark positions were evaluated at three time points: before surgery (T0), 6 months (T1) and 12 months (T2) after surgery. (Source: International Journal of Oral and Maxillofacial Surgery)
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Three-dimensional evaluation of postoperative stability: a comparative study between surgery-first and surgery-late protocols

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The main objective of this study was to compare the stability of the surgery-first and surgery-late approaches according to the standardized centre protocols, by three-dimensional evaluation after 1 year of follow-up. A retrospective study was designed that included a test group (surgery-first protocol) and a control group (surgery-late protocol), with a follow-up period of at least 1 year (average 14 months; range 12 –24 months). Stability was evaluated using linear and angular measurements by superimposing cone beam computed tomography images obtained at specific points in time: preoperatively, 1 month after surgery, and at the end of the orthodontic treatment. (Source: International Journal of Oral and Maxillofacial Surgery)
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