Vitamin D deficiency affects 1 billion people globally. It has an important role in bone homeostasis, brain development and modulation of the immune system and yet the impact of antenatal vitamin D ...deficiency on infant outcomes is poorly understood. We assessed the association of 25- hydroxyvitamin D levels (25-OHD) in late pregnancy and early infant growth and developmental outcomes in rural Vietnam.
A prospective cohort study of 960 women who had previously participated in a double-blind cluster randomized controlled trial of antenatal micronutrient supplementation in rural Vietnam was undertaken. Maternal 25-OHD concentration was measured at 32 weeks gestation, and infants were followed until 6 months of age. Main outcome measures were cognitive, motor, socio-emotional and language scores using the Bayley Scales of Infant Development, 3rd edition, and infant length-for-age z scores at 6 months of age.
60% (582/960) of women had 25-OHD levels <75 nmol/L at 32 weeks gestation. Infants born to women with 25-OHD deficiency (<37.5 nmol/L) had reduced developmental language scores compared to those born to women who were vitamin D replete (≥75 nmol/L) (Mean Difference (MD) -3.48, 95% Confidence Interval (CI) -5.67 to -1.28). For every 25 nmol increase in 25-OHD concentration in late pregnancy, infant length-for-age z scores at 6 months of age decreased by 0.08 (95% CI -0.15 to -0.02).
Low maternal 25- hydroxyvitamin D levels during late pregnancy are of concern in rural Vietnam, and are associated with reduced language developmental outcomes at 6 months of age. Our findings strengthen the evidence for giving vitamin D supplementation during pregnancy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily ...dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam.
This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (< 16 wk gestation) in 104 communes were assigned to daily iron-folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference MD 28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g; 95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56).
Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency.
Australia New Zealand Clinical Trials Registry 12610000944033.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
"Vaccine hesitancy" is a concept now frequently used in vaccination discourse. The increased popularity of this concept in both academic and public health circles is challenging previously held ...perspectives that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. A consultation study was designed to assess the opinions of experts and health professionals concerning the definition, scope, and causes of vaccine hesitancy in Canada. We sent online surveys to two panels (1- vaccination experts and 2- front-line vaccine providers). Two questionnaires were completed by each panel, with data from the first questionnaire informing the development of questions for the second. Our participants defined vaccine hesitancy as an attitude (doubts, concerns) as well as a behaviour (refusing some / many vaccines, delaying vaccination). Our findings also indicate that both vaccine experts and front-line vaccine providers have the perception that vaccine rates have been declining and consider vaccine hesitancy an important issue to address in Canada. Diffusion of negative information online and lack of knowledge about vaccines were identified as the key causes of vaccine hesitancy by the participants. A common understanding of vaccine hesitancy among researchers, public health experts, policymakers and health care providers will better guide interventions that can more effectively address vaccine hesitancy within Canada.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The extent to which influenza A and B infection differs remains uncertain.
Using active surveillance data from the Canadian Immunization Monitoring Program Active at 12 pediatric hospitals, we ...compared clinical characteristics and outcomes of children ≤16 years admitted with laboratory-confirmed influenza B or seasonal influenza A. We also examined factors associated with ICU admission in children hospitalized with influenza B.
Over 8 nonpandemic influenza seasons (2004-2013), we identified 1510 influenza B and 2645 influenza A cases; median ages were 3.9 and 2.0 years, respectively (P < .0001). Compared with influenza A patients, influenza B patients were more likely to have a vaccine-indicated condition (odds ratio OR = 1.30; 95% confidence interval CI = 1.14-1.47). Symptoms more often associated with influenza B were headache, abdominal pain, and myalgia (P < .0001 for all symptoms after adjustment for age and health status). The proportion of deaths attributable to influenza was significantly greater for influenza B (1.1%) than influenza A (0.4%); adjusted for age and health status, OR was 2.65 (95% CI = 1.18-5.94). A similar adjusted OR was obtained for all-cause mortality (OR = 2.95; 95% CI = 1.34-6.49). Among healthy children with influenza B, age ≥10 years (relative to <6 months) was associated with the greatest odds of ICU admission (OR = 5.79; 95% CI = 1.91-17.57).
Mortality associated with pediatric influenza B infection was greater than that of influenza A. Among healthy children hosptialized with influenza B, those 10 years and older had a significant risk of ICU admission.
Damage to the retinal pigment epithelium (RPE) is an early event in the pathogenesis of age-related macular degeneration (AMD). X-box binding protein 1 (XBP1) is a key transcription factor that ...regulates endoplasmic reticulum (ER) homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute respiratory infections and diarrhea remain the leading causes of infant morbidity and mortality, with a high burden of both pneumonia and diarrhea in South-East Asia. The aim of the study was ...to determine antenatal and early infant predictive factors for severe morbidity episodes during the first 6 months of life in Ha Nam province, Vietnam.
A prospective cohort study of 1049 infants, born to women who had previously participated in a cluster randomized controlled trial of antenatal micronutrient supplementation in rural Vietnam, was undertaken between 28th September 2010 and 8th Jan 2012. Infants were followed until 6 months of age, and the outcome measure was inpatient admission for suspected pneumonia or diarrheal illness during the first 6 months of life. Risk factors were assessed using univariable logistic regression and multiple logistic regression.
Of the 1049 infants seen at 6 months of age, 8.8 % required inpatient admission for suspected pneumonia and 4 % of infants required inpatient admission for diarrheal illness. One third of infants (32.8 %) were exclusively breast fed at 6 weeks of age. Exclusive breast feeding at 6 weeks of age significantly reduced the odds of inpatient admission for suspected pneumonia (Odds Ratio (OR) 0.39, 95 % Confidence Interval (CI) 0.20 to 0.75) and diarrheal illness (OR 0.37, 95 % CI 0.15 to 0.88).
Exclusive breast feeding in early infancy reduces the risk of severe illness from diarrhea and suspected pneumonia. Public health programs to reduce the burden of inpatient admission from diarrheal and respiratory illness in rural Vietnam should address barriers to exclusive breast feeding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Age-related macular degeneration (AMD) is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. In search of effective ...therapeutic agents, we tested curcumin, a naturally occurring compound with known anti-inflammatory and antioxidative properties, in a rat model of light-induced retinal degeneration (LIRD) and in retina-derived cell lines. We hypothesized that any compound effective against LIRD, which involves significant oxidative stress and inflammation, would be a candidate for further characterization for its potential application in AMD. We observed significant retinal neuroprotection in rats fed diets supplemented with curcumin (0.2% in diet) for 2 weeks. The mechanism of retinal protection from LIRD by curcumin involves inhibition of NF-κB activation and down-regulation of cellular inflammatory genes. When tested on retina-derived cell lines (661W and ARPE-19), pretreatment of curcumin protected these cells from H2O2-induced cell death by up-regulating cellular protective enzymes, such as HO-1, thioredoxin. Since, curcumin with its pleiotropic activities can modulate the expression and activation of many cellular regulatory proteins such as NF-κB, AKT, NRF2, and growth factors, which in turn inhibit cellular inflammatory responses and protect cells; we speculate that curcumin would be an effective nutraceutical compound for preventive and augmentative therapy of AMD.
When Alzheimer's is LATE: Why Does it Matter? Nelson, Peter T.; Schneider, Julie A.; Jicha, Gregory A. ...
Annals of neurology,
August 2023, Letnik:
94, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Recent therapeutic advances provide heightened motivation for accurate diagnosis of the underlying biologic causes of dementia. This review focuses on the importance of clinical recognition of ...limbic‐predominant age‐related TDP‐43 encephalopathy (LATE). LATE affects approximately one‐quarter of older adults and produces an amnestic syndrome that is commonly mistaken for Alzheimer's disease (AD). Although AD and LATE often co‐occur in the same patients, these diseases differ in the protein aggregates driving neuropathology (Aβ amyloid/tau vs TDP‐43). This review discusses signs and symptoms, relevant diagnostic testing, and potential treatment implications for LATE that may be helpful for physicians, patients, and families. ANN NEUROL 2023;94:211–222
Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrP
C
, ...by its infectious conformation, PrP
Sc
. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids. Some five decades later, detection of PrP
Sc
in free-ranging Norwegian (NO) reindeer and moose marked the first indication of CWD in Europe. To assess the properties of these emergent NO prions and compare them with NA CWD we used transgenic (Tg) and gene targeted (Gt) mice expressing PrP with glutamine (Q) or glutamate (E) at residue 226, a variation in wild type cervid PrP which influences prion strain selection in NA deer and elk. Transmissions of NO moose and reindeer prions to Tg and Gt mice recapitulated the characteristic features of CWD in natural hosts, revealing novel prion strains with disease kinetics, neuropathological profiles, and capacities to infect lymphoid tissues and cultured cells that were distinct from those causing NA CWD. In support of strain variation, PrP
Sc
conformers comprising emergent NO moose and reindeer CWD were subject to selective effects imposed by variation at residue 226 that were different from those controlling established NA CWD. Transmission of particular NO moose CWD prions in mice expressing E at 226 resulted in selection of a kinetically optimized conformer, subsequent transmission of which revealed properties consistent with NA CWD. These findings illustrate the potential for adaptive selection of strain conformers with improved fitness during propagation of unstable NO prions. Their potential for contagious transmission has implications for risk analyses and management of emergent European CWD. Finally, we found that Gt mice expressing physiologically controlled PrP levels recapitulated the lymphotropic properties of naturally occurring CWD strains resulting in improved susceptibilities to emergent NO reindeer prions compared with over-expressing Tg counterparts. These findings underscore the refined advantages of Gt models for exploring the mechanisms and impacts of strain selection in peripheral compartments during natural prion transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Severe falciparum malaria is a medical emergency characterised by potentially lethal vital organ dysfunction. Patient fatality rates even with parenteral artesunate treatment remain high. Despite ...considerable research into adjuvant therapies targeting organ and tissue dysfunction, none have shown efficacy apart from renal replacement therapy. Understanding the causal contributions of clinical and laboratory abnormalities to mortality is essential for the design and evaluation of novel therapeutic interventions.
We used a structural model causal inference approach to investigate causal relationships between epidemiological, laboratory, and clinical variables in patients with severe falciparum malaria enrolled in clinical trials and their in-hospital mortality. Under this causal model, we analysed records from 9,040 hospitalised children (0-12 years, n = 5,635) and adults (n = 3,405, 12-87 years) with severe falciparum malaria from 15 countries in Africa and Asia who were studied prospectively over the past 35 years. On admission, patient covariates associated with increased in-hospital mortality were severity of acidosis (odds ratio OR 2.10 for a 7-mEq/L increase in base deficit 95% CI 1.93-2.28), renal impairment (OR 1.71 for a 2-fold increase in blood urea nitrogen 95% CI 1.58, 1.86), coma (OR 3.59 95% CI 3.07-4.21), seizures (OR 1.40 95% CI 1.16-1.68), shock (OR 1.51 95% CI 1.14-1.99), and presumed pulmonary oedema (OR 1.58 95% CI 1.04-2.39). Lower in-hospital mortality was associated with moderate anaemia (OR 0.87 for a decrease of 10 percentage points in haematocrit 95% CI 0.80-0.95). Circulating parasite density was not associated with mortality (OR 1.02 for a 6-fold increase 95% CI 0.94-1.11), so the pathological effects of parasitaemia appear to be mediated entirely by the downstream effects of sequestration. Treatment with an artemisinin derivative decreased mortality compared with quinine (OR 0.64 95% CI 0.56-0.74). These estimates were consistent across children and adults (mainly representing African and Asian patients, respectively). Using inverse probability weighting, transfusion was not estimated to be beneficial in children with admission haematocrit values between 15% and 25% (OR 0.99 95% CI 0.97-1.02). Except for the effects of artemisinin treatment and transfusion, causal interpretations of these estimates could be biased by unmeasured confounding from severe bacterial sepsis, immunity, and duration of illness.
These data suggest that moderate anaemia is associated with a reduced risk of death in severe falciparum malaria. This is possibly a direct causal association. The severe anaemia threshold criteria for a definition of severe falciparum malaria should be reconsidered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
