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Αλέξανδρος Γ. Σφακιανάκης

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Wednesday, October 12, 2022

Effect of malaria and malaria chemoprevention regimens in pregnancy and childhood on neurodevelopmental and behavioral outcomes in children at 12, 24 and 36 months: a randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Malaria in pregnancy has been associated with worse cognitive outcomes in children, but its association with behavioral outcomes and the effectiveness of malaria chemoprevention on child neurodevelopment are not well characterized.
Methods
To determine if more effective malaria chemoprevention in mothers and their children results in better neurodevelopment, 305 pregnant women were randomly assigned to 3 doses of sulfadoxine-pyrimethamine, 3 doses of dihydroartemisinin-piperaquine (DP) or monthly DP during pregnancy, and their 293 children were assigned to DP every 3 months or monthly DP from 2 to 24 months of age. Cognition, language and motor function were assessed at 12, 24 and 36 months of age, and attention, memory, behavior and executive function at 24 and 36 months of age.
Results
Children of mothers with vs. without malaria in pregnancy had worse scores on cognitive, behavioral and executive function outcomes at 24 months. Clinical malaria in children within the first 12 months was similarly associated with poorer scores in behavior and executive function at 24 months, language at 24 and 36 months, and motor function scores at 36 months. However, more effective malaria chemoprevention in the mothers and children was not associated with better outcomes.
Conclusions
Malaria in pregnancy was associated with worse cognitive, behavioral and executive function scores in affected children, but more effective malaria chemoprevention measures did not result in better outcomes. Malaria chemoprevention prior to and early in gestation and with even higher efficacy in mothers and children may be required to prevent neurodevelopmental impairment in children.
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Improved Survival after Liver Transplantation for Patients with HIV and HIV/HCV Coinfection in the INSTI and DAA eras

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Patients with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTI) and direct-acting antivirals (DAA) changed the treatment landscape for HIV and HCV, respectively; their impact on LT outcomes remains unclear.
Methods
This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before vs. after approval of INSTI and in patients with HIV/HCV coinfection who received LT before vs after approval of DAA. In secondary analysis, we compared the outcomes in the different eras with those of propensity score (PS) matched control cohorts of LT recipients without HIV or HCV infection.
Results
HIV monoinfected LT recipients did not experience a significant improvement in su rvival between the pre-INSTI and INSTI recipients with HIV (aHR 0.70 [0.36-1.34). However, recipients with HIV/HCV coinfection in the DAA era had a 47% reduction (aHR 0.53 [0.31-9.2] in one-year mortality than co-infected recipients in the pre-DAA era. Compared to non-HIV or HCV recipients, HIV monoinfected recipients had higher mortality during the pre-INSTI era (aHR, ), but survival was comparable between groups during the INSTI era (aHR, ). HIV/HCV coinfected recipients also experienced comparable survival during the DAA era compared to non-HIV or HCV recipients (aHR, ).
Conclusions
Post-LT survival for patients with HIV monoinfection and HIV/HCV coinfection has improved with the introduction of INSTI and DAA therapy, suggesting that LT has become safer in these populations.
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Maternal diet during breastfeeding in correlation to calcium and phosphorus concentrations in human milk

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

The impact of maternal diet on minerals concentration in human milk (HM) remains unclear. The main aim of this study was to investigate the relationship between maternal dietary intake and calcium and phosphorus concentrations in HM. Furthermore, we aimed to evaluate the intake of both minerals by exclusively breastfed infants.

Methodology

HM samples were obtained from 30 mothers at 6-8 weeks postpartum. Each mother was asked to express pre- and post-feeding milk four times during 24-h period (6.00-12.00, 12.00-18.00, 18.00-24.00, 24.00-6.00). Maternal dietary assessment was based on food frequency questionnaire and 3-day dietary records. Analyzed minerals were determined by inductively coupled plasma mass spectrometer (NexION 300D ICP Mass Spectrometer, Perkin Elmer SCIEX, USA).

Results

The mean concentrations of calcium and phosphorus in HM samples were 278.7 ± 61.0 mg/L and 137.1 ± 21.9 mg/L, respectively, maintaining 2:1 ratio b y weight. The concentration of both minerals was correlated with each other (r=0.632, p=<0.001). The infants' mean calcium intake was 149.53 ± 36.41 mg/L and for phosphorus it was 74.62 ± 19.41 mg/L. The risk of insufficient intake of calcium was reported in 60% of infants (n=18). Spearman/Pearson correlation coefficients did not reveal any correlations between HM calcium concentration and maternal diet, contrary to HM phosphorus concentration, which was positively correlated with energy (r=0.369, p=0.045), total protein (r=0.464, p=0.01), calcium (r=385, p=0.036), phosphorus (r=501, p=0.005), niacin (p<0.001) and pyridoxine (r=382, 0.037) intake. However, in multivariable analysis we observed that maternal dietary intake of both minerals had positive influence on their concentration in HM.

Conclusion

Maternal calcium and phosphorus intake influenced concentration of both minerals in HM, however the relationship was rather weak. Additionally, we observed that c alcium intake by most of the exclusively breastfed infants was insufficient to meet the recommended daily intake.

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Two-Stage Modeling to Identify How Colorectal Cancer Risk Changes With Period and Cohort

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Colorectal cancer (CRC) incidence rates have decreased among adults aged 50 and older while increasing in adults under age 50. Understanding these trends is challenging due to the multiple related time scales of age, period of diagnosis, and birth cohort. We analyzed rectal, distal colon, and proximal colon cancer incidence rates for individuals aged 20 and older from the Surveillance, Epidemiology, and End Results program for diagnosis years 1978-2017. We used a two-stage generalized linear model to describe age, period, and cohort effects for incidence. We first estimated birth cohort effects among people under 45. We used these results to specify prior distributions for cohort effects in a Bayesian model to estimate period effects among people 45 and older. There was no evidence of period effects for people under age 45. Risk for rectal and distal colon cancer increased for later birth cohorts. Compared to the 1943-1952 birth cohort, the 1983- 1992 birth cohort had 2.1 times the risk of rectal cancer, 1.8 times the risk of distal colon cancer and 1.3 times the risk of proximal colon cancer. For people over 45, period effects show declines in CRC risk that are attributable to screening.
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Targeting integrin α2 as potential strategy for radiochemosensitization of glioblastoma

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Glioblastoma (GBM) is a fast-growing primary brain tumor characterized by high invasiveness and resistance. This results in poor patient survival. Resistance is caused by many factors, including cell-extracellular matrix (ECM) interactions. Here, we addressed the role of adhesion protein integrin α2, which we identified in a high-throughput screen for novel potential targets in GBM cells treated with standard therapy consisting of temozolomide (TMZ) and radiation.
Methods
In our study, we used a range of primary/stem-like and established GBM cell models in vitro and in vivo. To identify regulatory mechanisms, we employed high-throughput kinome profiling, Western blotting, immunofluorescence staining, reporter and activity assays.
Results
Our data showed that integrin α2 is overexpressed in GBM compared to normal brain and, that its deletion causes radiochemosensitization. Similarly, invasion and adhesion w ere significantly reduced in TMZ-irradiated GBM cell models. Furthermore, we found that integrin α2-knockdown impairs proliferation of GBM cells without affecting DNA damage repair. At the mechanistic level, we found that integrin α2 affects the activity of activating transcription factor 1 (ATF1) and modulates the expression of extracellular signal-regulated kinase 1 (ERK1) regulated by extracellular signals. Finally, we demonstrated that integrin α2-deficiency inhibits tumor growth and thereby prolongs survival of mice with orthotopically growing GBM xenografts.
Conclusions
Taken together our data suggest that integrin α2 may be a promising target to overcome GBM resistance to radio- and chemotherapy. Thus, it would be worth evaluating how efficient and safe the adjuvant use of integrin α2 inhibitors is to standard radio(chemo)therapy in GBM.
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Investigating the Effect of Cochlear Synaptopathy on Envelope Following Responses Using a Model of the Auditory Nerve

alexandrossfakianakis shared this article with you from Inoreader
AbstractThe healthy auditory system enables communication in challenging situations with high levels of background noise. Yet, despite normal sensitivity to pure tones, many listeners complain about having difficulties in such situations. Recent animal studies demonstrated that noise overexposure that produces temporary threshold shifts can cause the loss of auditory nerve (AN) fiber synapses (i.e., cochlear synaptopathy, CS), which appears to predominantly affect medium- and low-spontaneous rate (SR) fibers. In the present study, envelope following response (EFR) magnitude-level functions were recorded in normal hearing (NH) threshold and mildly hearing-impaired (HI) listeners with thresholds elevated above 2  kHz. EFRs were elicited by sinusoidally amplitude modulated (SAM) tones presen...
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Vibration Measurements of the Gerbil Eardrum Under Quasi-static Pressure Sweeps

alexandrossfakianakis shared this article with you from Inoreader
This study is a continuation of our previous work in which the vibration response of the gerbil eardrum was measured in vivo under quasi-static pressure steps. In this study, we delivered a continuous pressure sweep to the middle ear and measured the vibration response at four locations for six gerbils. Vibrations were recorded using a single-point laser Doppler vibrometer and glass-coated reflective beads (diameter  ~ 40 µm) at the umbo and on the mid-manubrium, posterior pars tensa and anterior pars tensa.The vibration magnitudes were similar to those in the previous step-wise pressurization experiments. Most gerbils showed repeatability within less than 10  dB for consecutive cycles. As described in the previous study, as the frequency was increased at ambient pressure, the vibra...
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Clinical features and overall survival of osteosarcoma of the mandible

alexandrossfakianakis shared this article with you from Inoreader
This study describes the clinical features and prognosis of mandibular osteosarcoma. The SEER database was utilized to identify cases of mandibular osteosarcoma diagnosed between 2004 and 2015. Sex, age, grade, histological subtype, tumor size, tumor extension, presence of metastasis at diagnosis, and therapeutic intervention were determined. (Source: International Journal of Oral and Maxillofacial Surgery)
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Using indocyanine green angiography to achieve complete engraftment of pectoralis major myocutaneous flaps

alexandrossfakianakis shared this article with you from Inoreader
This report describes the usefulness of indocyanine green angiography (ICGA) to achieve complete engraftment of the PMMC flap. Five patients with oral cancer underwent reconstruction with a PMMC flap after cancer ablation. During the skin paddle design and flap elevation, the blood supply to the flap was assessed by ICGA. (Source: International Journal of Oral and Maxillofacial Surgery)
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