Influence of innate immune activation on endocrine and metabolic pathways in infancy

Prematurity is the leading cause of neonatal morbidity and mortality worldwide. Premature infants often require extended hospital stays, with increased risk of developing infection compared with term infants. A picture is emerging of wide-ranging deleterious consequences resulting from innate immune system activation in the newborn infant. Those who survive infection have been exposed to a stimulus that can impose long-lasting alterations into later life. In this review, we discuss sepsis-driven alterations in integrated neuroendocrine and metabolic pathways and highlight current knowledge gaps in respect of neonatal sepsis. We review established biomarkers for sepsis and extend the discussion to examine emerging findings from human and animal models of neonatal sepsis that propose novel biomarkers for early identification of sepsis. Future research in this area is required to establish a greater understanding of the distinct neonatal signature of early and late-stage infection, to improve diagnosis, curtail inappropriate antibiotic use and promote precision medicine through a biomarker-guided empirical and adjunctive treatment approach for neonatal sepsis. There is an unmet clinical need to decrease sepsis-induced morbidity in neonates, to limit and prevent adverse consequences in later life and decrease mortality.

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The Joint-Brain Axis: Insights From Rheumatoid Arthritis on the Crosstalk Between Chronic Peripheral Inflammation and the Brain

Frontiers in Immunology ◽

10.3389/fimmu.2020.612104 ◽

2020 ◽

Vol 11 ◽

Author(s):

Patrick Süß ◽

Tobias Rothe ◽

Alana Hoffmann ◽

Johannes C. M. Schlachetzki ◽

Jürgen Winkler

Keyword(s):

Rheumatoid Arthritis ◽

Current Knowledge ◽

Later Life ◽

Chronic Inflammatory Disease ◽

Peripheral Inflammation ◽

Cellular Mechanisms ◽

Increased Risk ◽

Neuropsychiatric Diseases ◽

Patients At Risk ◽

The Impact

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive polyarthritis. Beyond joint pathology, RA is associated with neuropsychiatric comorbidity including depression, anxiety, and an increased risk to develop neurodegenerative diseases in later life. Studies investigating the central nervous system (CNS) in preclinical models of RA have leveraged the understanding of the intimate crosstalk between peripheral and central immune responses. This mini review summarizes the current knowledge of CNS comorbidity in RA patients and known underlying cellular mechanisms. We focus on the differential regulation of CNS myeloid and glial cells in different mouse models of RA reflecting different patterns of peripheral immune activation. Moreover, we address CNS responses to anti-inflammatory treatment in human RA patients and mice. Finally, to illustrate the bidirectional communication between the CNS and chronic peripheral inflammation, we present the current knowledge about the impact of the CNS on arthritis. A comprehensive understanding of the crosstalk between the CNS and chronic peripheral inflammation will help to identify RA patients at risk of developing CNS comorbidity, setting the path for future therapeutic approaches in both RA and neuropsychiatric diseases.

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Aetiologies and risk factors for neonatal sepsis and pneumonia mortality among Alaskan infants

Epidemiology and Infection ◽

10.1017/s0950268805004449 ◽

2005 ◽

Vol 133 (5) ◽

pp. 877-881 ◽

Cited By ~ 6

Author(s):

B. D. GESSNER ◽

L. CASTRODALE ◽

M. SORIANO-GABARRO

Keyword(s):

Risk Factors ◽

Neonatal Sepsis ◽

Rate Ratio ◽

Neonatal Period ◽

Group B Streptococcus ◽

Sepsis Mortality ◽

Term Infants ◽

Gram Positive Bacteria ◽

Increased Risk ◽

Group B

We evaluated all fatal neonatal sepsis and pneumonia cases occurring in Alaska during 1992–2000. Risk factors were evaluated using a database of all births occurring during the study period. Of 32 cases, group B streptococcus (GBS) was isolated from 21% (all <7 days of age), Candida spp. from 19% (all >7 days of age), non-GBS Gram-positive bacteria from 50% (53% <7 days of age), and Gram-negative infections from 38% (58% <7 days of age). Infants born at <37 weeks gestation accounted for 72% of cases and had an increased risk of GBS [rate ratio (RR) 9·1, 95% confidence interval (CI) 2·0–41] and non-GBS (RR 40, 95% CI 16–101) disease. Neonatal sepsis mortality has become an outcome concentrated among pre-term infants. Aetiologies include GBS during the early neonatal period, Candida spp. during the late neonatal period, and other bacteria during both periods.

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Environmental influences on healthy and active ageing: a systematic review

Ageing and Society ◽

10.1017/s0144686x1200116x ◽

2012 ◽

Vol 34 (4) ◽

pp. 590-622 ◽

Cited By ~ 81

Author(s):

MICHAEL ANNEAR ◽

SALLY KEELING ◽

TIM WILKINSON ◽

GRANT CUSHMAN ◽

BOB GIDLOW ◽

...

Keyword(s):

Current Knowledge ◽

Environmental Influences ◽

Theory Development ◽

Antisocial Behaviour ◽

Local Environment ◽

Later Life ◽

Activity Participation ◽

Future Research ◽

Active Ageing ◽

Adult Health

ABSTRACTThis paper explores the evidence for environmental influences on older adult health and activity participation, identifies current knowledge gaps and limitations within this literature, and offers recommendations for future research via a systematic appraisal of 83 quantitative and qualitative studies. A Cochrane-type review procedure was followed, which incorporated structured database searches, inclusion and exclusion criteria, quality appraisal of included studies, and peer review. The review findings identify support for both personal and environmental influences on health and activity participation in later life. Reported personal influences include ethnicity and cultural norms, energy and motivation, sex, age, education, genetic heritage, self-efficacy, and personal financial circumstances. Reported environmental influences on activity participation include climate, level of pollution, street lighting, traffic conditions, accessibility and appropriateness of services and facilities, socio-economic conditions, aesthetics, pedestrian infrastructure, community life, exposure to antisocial behaviour, social network participation, environmental degradation, level of urbanism, exposure to natural settings, familiarity with local environment and others. Recommendations for future research include the need for innovative research methods; involvement of older adults as research collaborators; investigation of wider aspects of the active ageing concept; in-depth assessment of the environmental characteristics of areas; investigation of the pathways leading from environment to health and activity participation; and more theoretically informed research or increased contribution of research to theory development.

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PS-221 Lower Maternal/neonatal Vitamin D Levels Are Associated With Increased Risk Of Early Onset Neonatal Sepsis In Term Infants

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307384.520 ◽

2014 ◽

Vol 99 (Suppl 2) ◽

pp. A192.3-A193

Author(s):

M Cetinkaya ◽

F Cekmez ◽

G Buyukkale ◽

T Erener-Ercan ◽

F Demir ◽

...

Keyword(s):

Vitamin D ◽

Neonatal Sepsis ◽

Early Onset ◽

Term Infants ◽

Increased Risk ◽

Vitamin D Levels

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Hormones and endometrial carcinogenesis

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2016-0005 ◽

2016 ◽

Vol 25 (2) ◽

Cited By ~ 4

Author(s):

Areege Kamal ◽

Nicola Tempest ◽

Christina Parkes ◽

Rafah Alnafakh ◽

Sofia Makrydima ◽

...

Keyword(s):

Metabolic Pathways ◽

Current Knowledge ◽

Ovarian Hormones ◽

Western World ◽

Future Research ◽

Normal Human ◽

And Function ◽

Human Endometrial Cell ◽

Unopposed Oestrogen

AbstractEndometrial cancer (EC) is the commonest gynaecological cancer in the Western World with an alarmingly increasing incidence related to longevity and obesity. Ovarian hormones regulate normal human endometrial cell proliferation, regeneration and function therefore are implicated in endometrial carcinogenesis directly or via influencing other hormones and metabolic pathways. Although the role of unopposed oestrogen in the pathogenesis of EC has received considerable attention, the emerging role of other hormones in this process, such as androgens and gonadotropin-releasing hormones (GnRH) is less well recognised. This review aims to consolidate the current knowledge of the involvement of the three main endogenous ovarian hormones (oestrogens, progesterone and androgens) as well as the other hormones in endometrial carcinogenesis, to identify important avenues for future research.

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Crosstalk Between Staphylococcus aureus and Innate Immunity: Focus on Immunometabolism

Frontiers in Immunology ◽

10.3389/fimmu.2020.621750 ◽

2021 ◽

Vol 11 ◽

Author(s):

Christopher M. Horn ◽

Tammy Kielian

Keyword(s):

Staphylococcus Aureus ◽

Metabolic Pathways ◽

Biofilm Formation ◽

Bacterial Infections ◽

Current Knowledge ◽

Innate Immune ◽

Community Settings ◽

Leukocyte Activation ◽

Inflammatory Status ◽

Novel Therapeutic Strategies

Staphylococcus aureus is a leading cause of bacterial infections globally in both healthcare and community settings. The success of this bacterium is the product of an expansive repertoire of virulence factors in combination with acquired antibiotic resistance and propensity for biofilm formation. S. aureus leverages these factors to adapt to and subvert the host immune response. With the burgeoning field of immunometabolism, it has become clear that the metabolic program of leukocytes dictates their inflammatory status and overall effectiveness in clearing an infection. The metabolic flexibility of S. aureus offers an inherent means by which the pathogen could manipulate the infection milieu to promote its survival. The exact metabolic pathways that S. aureus influences in leukocytes are not entirely understood, and more work is needed to understand how S. aureus co-opts leukocyte metabolism to gain an advantage. In this review, we discuss the current knowledge concerning how metabolic biases dictate the pro- vs. anti-inflammatory attributes of various innate immune populations, how S. aureus metabolism influences leukocyte activation, and compare this with other bacterial pathogens. A better understanding of the metabolic crosstalk between S. aureus and leukocytes may unveil novel therapeutic strategies to combat these devastating infections.

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Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants

Journal of Perinatology ◽

10.1038/jp.2014.146 ◽

2014 ◽

Vol 35 (1) ◽

pp. 39-45 ◽

Cited By ~ 50

Author(s):

M Cetinkaya ◽

F Cekmez ◽

G Buyukkale ◽

T Erener-Ercan ◽

F Demir ◽

...

Keyword(s):

Vitamin D ◽

Neonatal Sepsis ◽

Early Onset ◽

Term Infants ◽

Increased Risk ◽

Vitamin D Levels ◽

Lower Vitamin

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Folic acid in ruminant nutrition: a review

British Journal Of Nutrition ◽

10.1017/s0007114508051556 ◽

2008 ◽

Vol 101 (2) ◽

pp. 153-164 ◽

Cited By ~ 7

Author(s):

Veronika Ragaller ◽

Liane Hüther ◽

Peter Lebzien

Keyword(s):

Folic Acid ◽

Metabolic Pathways ◽

Current Knowledge ◽

Serum Folate ◽

Future Research ◽

Methionine Metabolism ◽

Ruminant Nutrition ◽

Micro Organisms ◽

Forage:Concentrate Ratio ◽

Very High

Folic acid plays an essential role in DNA and methionine metabolism. Micro-organisms in the rumen can synthesise folates, but it has not been verified that these amounts are sufficient to achieve the best efficiency of dairy cows. However, the amount of folates synthesised in the rumen could possibly, to some extent, be affected by the forage:concentrate ratio. Degradation of orally supplemented folic acid in the rumen seems to be very high (about 97 %), as supplementation of folic acid hardly increases folate concentrations in the digesta at the duodenum. However, it must be considered that dietary supplements of folic acid higher than 0·5 mg/kg body weight increased serum folate concentrations in all available studies and milk folate concentrations in most studies. Additionally, milk production tended to be increased in some studies. Therefore, degradation of folic acid in the rumen may be overestimated as folates can be absorbed at the proximal duodenum. For future research it is necessary to consider the whole flow and the metabolic pathways of folates from the rumen to duodenum, blood, tissue, milk and transfer to calf to declare requirement values for cows. Consequently, the present review discusses current knowledge and emphasises areas for future research.

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Infant BMI peak as a predictor of overweight and obesity at age 2 years in a Chinese community-based cohort

BMJ Open ◽

10.1136/bmjopen-2016-015122 ◽

2017 ◽

Vol 7 (10) ◽

pp. e015122 ◽

Cited By ~ 8

Author(s):

Jie Sun ◽

Bright I Nwaru ◽

Jing Hua ◽

Xiaohong Li ◽

Zhuochun Wu

Keyword(s):

Childhood Obesity ◽

Polynomial Regression ◽

Growth Curves ◽

Overweight And Obesity ◽

Future Research ◽

Peak Time ◽

Chinese Community ◽

Community Based ◽

Term Infants ◽

Increased Risk

ObjectivesInfant body mass index (BMI) peak has proven to be a useful indicator for predicting childhood obesity risk in American and European populations. However, it has not been assessed in China. We characterised infant BMI trajectories in a Chinese longitudinal cohort and evaluated whether BMI peak can predict overweight and obesity at age 2 years.MethodsSerial measurements (n=6–12) of weight and length were taken from healthy term infants (n=2073) in a birth cohort established in urban Shanghai. Measurements were used to estimate BMI growth curves from birth to 13.5 months using a polynomial regression model. BMI peak characteristics, including age (in months) and magnitude (BMI, in kg/m2) at peak and prepeak velocities (in kg/m2/month), were estimated. The relationship between infant BMI peak and childhood BMI at age 2 years was examined using binary logistic analysis.ResultsMean age at peak BMI was 7.61 months, with a magnitude of 18.33 kg/m2. Boys (n=1022) had a higher average peak BMI (18.60 vs 18.07 kg/m2, p<0.001) and earlier average achievement of peak value (7.54 vs 7.67 months, p<0.05) than girls (n=1051). With 1 kg/m2increase in peak BMI and 1 month increase in peak time, the risk of overweight at age 2 years increased by 2.11 times (OR 3.11; 95% CI 2.64 to 3.66) and 35% (OR 1.35; 95% CI 1.21 to 1.50), respectively. Similarly, higher BMI magnitude (OR 2.69; 95% CI 2.00 to 3.61) and later timing of infant BMI peak (OR 1.35; 95% CI 1.08 to 1.68) were associated with an increased risk of childhood obesity at age 2 years.ConclusionsWe have shown that infant BMI peak is valuable for predicting early childhood overweight and obesity in urban Shanghai. Because this is the first Chinese community-based cohort study of this nature, future research is required to examine infant populations in other areas of China.

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A Retrospective Review of Neonatal Sepsis among GBS-Colonized Women Undergoing Planned Cesarean Section after Labor Onset or Rupture of Membranes

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/2020/4365259 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Fadi B. Yahya ◽

Matthew A. Hathcock

Keyword(s):

Cesarean Section ◽

Neonatal Sepsis ◽

Group B Streptococcus ◽

Term Infants ◽

Mortality And Morbidity ◽

Sepsis Diagnosis ◽

Increased Risk ◽

Intrapartum Antibiotic ◽

To Receive ◽

Missed Opportunity

Background. Sepsis is a leading cause of mortality and morbidity in neonates, with group B streptococcus (GBS) remaining the most frequent pathogen isolated from term infants. Surveillance data showed that the majority of cases of early-onset GBS disease were neonates born to women who either received no or suboptimal intrapartum antibiotic prophylaxis with a notable portion of those women having a missed opportunity to receive ≥4 hours of chemoprophylaxis. Women planning delivery by cesarean section who present in labor or rupture of membranes prior to their scheduled surgery are unlikely to receive optimal GBS chemoprophylaxis and thus their neonates are at risk of having sepsis. Materials and Methods. A retrospective cohort study of women-infant dyads was extracted from the Consortium on Safe Labor dataset. Women who had an unlabored cesarean section at ≥37+0 week gestation were selected and divided into four groups based on GBS status and timing of cesarean section with respect to onset of labor or rupture of membranes. The rate of neonatal sepsis and the patterns of intrapartum antibiotic chemoprophylaxis were determined. Results. The sepsis rate (4.5%) among neonates of GBS-colonized women having their unlabored cesarean section after onset of labor or rupture of membranes was significantly higher than that in any other group in this study. In this group, 9.4% of women received chemoprophylaxis for ≥4 hours, while 31% had a missed opportunity to receive ≥4 hours of chemoprophylaxis. Conclusion. This study suggests that neonates of GBS-colonized women having a planned cesarean section after onset of labor or rupture of membranes are at increased risk of having a sepsis diagnosis. This finding suggest the need for additional studies to assess the risk of sepsis among neonates of women in this group.

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