Nutrition in preschool children and later risk of obesity: a systematic review and meta analysis

Objectives and study: Nutrition in infants and preschool children has been suggested to influence the risk of later obesity. However, the evidence for this association is conflicting and few studies have investigated this prospectively or considered the role of energy and specific macronutrients. Here we report a systematic review and meta-analyis of studies that tested the hypothesis that nutrition in the preschool period, between the ages of 6 months and 3 years, is associated with later obesity risk. Methods: MEDLINE, EMBASE and CENTRAL databases were searched from January 1988 to June 2015 for studies reporting nutritional intake in infants and preschool children aged 6-36 months and later measures of obesity. Bibliographies of included studies were hand searched and authors and other experts consulted to identify omissions. We included all studies that investigated dietary energy and/or macronutrient intake during 6-36 months in relation to later measures of obesity. Methodological quality was assessed using the Downs and Black checklist designed specifically to appraise both randomised and non-randomised studies. The checklist was adapted to include aspects of particular relevance to studies investigating nutritional exposures. Two reviewers independently scored studies against the 28 item checklist which included questions on study reporting, external validity, internal validity (bias and confounding), and statistical power. A statistician independently scored questions relating to statistical methods and their decision was final. Data from studies amenable to meta-analysis were analysed using STATA (StataCrop 12, Texas). For continuous outcomes, results were expressed as standardised mean difference (SMD) between the high and low protein intake groups. For dichotomous outcomes, results for each study were expressed as relative risk (RR). Both dichotomous and continuous outcomes were presented with 95% confidence intervals (CI). Between-study heterogeneity was assessed by the Q and I2 statistics. Results: 24 eligible articles (comprising 16 primary studies) were included in a narrative synthesis, and 13 studies in a random-effects meta-analysis. A higher protein intake was associated with later risk of obesity in 15 studies. In 13 studies included in the meta-analysis protein in the preschool period was associated with higher BMI z-score later in childhood (pooled effect size: 0.28 z-scores, 95% CI 0.20 to 0.35)(Figure 1). There was no significant hererogeneity between studies (I2 0.0%, p = 0.932). Associations of energy, fat and carbohydrate were inconclusive. Conclusion: Our findings suggest that nutrition and particularly high protein intake in infants and preschool children is important for risk of later obesity. Although further experimental data are required to establish causality, these findings suggest that optimising the protein intake of these children could be important for their long term health

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Transforming growth factor β (TGF-β) superfamily signaling pathways are ubiquitous and essential for several cellular and physiological processes. The overexpression of TGF-β results in excessive fibrosis in multiple human disorders. Among them, stiff skin syndrome (SSS) is an ultrarare and untreatable condition characterized by the progressive thickening and hardening of the dermis, and acquired joint limitations. SSS is distinct in a widespread form, caused by recurrent germline variants of FBN1 encoding a key molecule of the TGF-β signaling, and a segmental form with unknown molecular basis. Here, we report a 12-year-old female with segmental SSS, affecting the right upper limb with acquired thickening of the dermis evident at the magnetic resonance imaging, and progressive limitation of the elbow and shoulder. To better explore the molecular and cellular mechanisms that drive segmental SSS, several functional studies on patient’s fibroblasts were employed. We hypothesized an impairment of TGF-β signaling and, consequently, a dysregulation of the associated downstream signaling. Lesional fibroblast studies showed a higher phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), increased levels of nuclear factor-kB (NFkB), and a nuclear accumulation of phosphorylated Smad2 via Western blot and microscopy analyses. Quantitative PCR expression analysis of genes encoding key extracellular matrix proteins revealed increased levels of COL1A1, COL3A1, AGT, LTBP and ITGB1, while zymography assay reported a reduced metalloproteinase 2 enzymatic activity. In vitro exposure of patient’s fibroblasts to losartan led to the partial restoration of normal transforming growth factor β (TGF-β) marker protein levels. Taken together, these data demonstrate that in our patient, segmental SSS is characterized by the overactivation of multiple TGF-β signaling pathways, which likely results in altered extracellular matrix composition and fibroblast homeostasis. Our results for the first time reported that aberrant TGF-β signaling may drive the pathogenesis of segmental SSS and might open the way to novel therapeutic approaches

Benign neonatal pustolosis (BNP) / TO WORRY OR NOT TO WORRY

Benign neonatal pustolosis (BNP) comprehend a group of clinical diseases characterized by transient pustules or vescico-pustular lesions on newborn skin. These are asymptomatic and self-limiting conditions including benign cephalic pustolosis (BCP). A 40 days old girl was conducted to our Pediatric Unit for the appearance of multiple vescico-pustular lesions with serous sterile content on her forehead. She was born at term, had a regular perinatal period and never reported cutaneous problems. No lotions or creams for and after her baths were used and no direct contact to sunlight was described. At the time of consultation, she was in excellent health conditions. On suspicion of BCP, we did not prescribe exams or local and/or systemic treatments but indicated a strict follow-up with clinical revaluation after 3 days. At follow-up, the infant did not have clinical problems and her pustular lesions had begun to disappear. After 7 days, all pustules had completely disappeared without leaving any scar. Dermatosis that occur during the neonatal period can be infectious or sterile, such as BNP. Frequently, BNP are secondary to a physiological skin response or to environmental factors. They are benign, self-limited, asymptomatic cutaneous conditions that present during the first days of life. Their diagnosis is clinical but, sometimes, can require some investigations, principally non-invasive, to exclude more severe diseases. BNP include erythema toxicum neonatorum, transient neonatal pustular melanosis and BCP. BCP was first described by Aractingi in 1991. There is no consensus about its prevalence, which is estimated between 10% and 60%. Its presentation is asymptomatic and self-limiting and is characterized by numerous papules and pustules located on the face and scalp with onset between 5 days and approximately 3 weeks of age of the newborn. Numerous studies evaluated the possible role of Malassezia in the etiopathogenesis of BCP. Nevertheless, this correlation has not been demonstrated so far. In conclusion, the presence of pustules in newborns is always a reason of concern for parents and doctors, since neonatal skin is more vulnerable to bacterial, viral and fungal infections. These lesions can be a real challenge for clinicians who have to recognize serious diseases requiring hospitalisation from benign transient conditions, avoiding superfluous exams, treatments and worrie

TICK WITH TREAT

Ticks can determine various local reactions, among which scarring and nonscarring inflammatory alopecia. We describe a case of nonscarring alopecia in a two-year-old girl of Romanian origin who reported a recent history of tick bite. She referred to our pediatric department with diffuse alopecia of the scalp, in which there was an erythematous nodule, presumed site of the tick bite accursed two months prior. She did not develop fever, arthralgias or other systemic symptoms. In order to exclude autoimmune diseases and infectious etiologies, we performed laboratory exams, such as anti-thyroid, antinuclear, anti-transglutaminase, TORCH and anti-Borrelia antibodies, resulted negative. A punch biopsy specimen from the scalp (0.4×0.3×0.2 cm) revealed fibrosis of the derma and the peripheric areas of pili-sebaceous annexes. The following month, we observed a rapid centrifugal progression to total alopecia. Thus, we decided to attempt therapy with topic corticosteroids followed by a progressive hair regrowth during the following four months. Tick bite alopecia was first described in 1921. Since then, a few other cases have been reported in the international literature. The characteristic manifestation is a single zone of alopecia, often with a centrifugal spread, that appears 1–2 weeks after the tick removal. Sometimes, it can be associated with a central eschar, representing the site of tick bite. The nonscarring forms of alopecia manifest as ‘moth-eaten’ patches or, in alternative, as nodular or blood-crusted lesions. Clinically, patients may present with pain, pruritus or swelling. The precise mechanism for hair loss is not well understood but it is assumed to be caused by the host inflammatory response to tick saliva antigens. The result is the destruction of hair follicles or the alteration of the catagen/telogen phase. Histologic findings may show a heterogeneous inflammatory infiltrate and areas of fibrosis. The international literature does not report effective therapy for tick bite alopecia, while treatment with topic corticosteroids for alopecia areata is recognized. Prognosis is favourable with a complete hair regrowth usually within 3 months, although in some cases alopecia is reported to persist for 5 year

Un caso atipico di stridore e dispnea, dal sospetto diagnostico alla terapia

Si descrive un caso clinico caratterizzato da stridore e dispnea, dal sospetto diagnostico alla terapia. Il caso si segnala per la atipicità della presentazione clinica

HUMAN METAPNEUMOVIRUS RESPONSIBLE FOR A SEVERE ERYTHEMA MULTIFORME: AN UNUSUAL ASSOCIATION

Erythema Multiforme (EM) is an acute immune-mediated condition characterized by the appearance of typical target-like lesions on the skin. They most commonly appear in a symmetrical distribution on the extensor surfaces of the acral extremities and subsequently spread in a centripetal way. EM ‘major’ involves oral, genital and ocular mucosae with erosions or bullae. Although cutaneous lesions are usually asymptomatic, EM can be caused by drugs, autoimmune disease, malignancy, irradiation, sarcoidosis and in 90 percent of cases by infections (viral, bacterial, fungal). Herpes Simplex virus is the most frequent etiologic agent. Mycoplasma Pneumoniae infection is another important cause of EM, particularly in children. Laboratory findings are not specific and clinical finding are necessary for diagnosis. A skin biopsy should be performed when the diagnosis is unclear. CASE REPORT: 14 year old male came to our attention for the appearance of cutaneous lesions, accompanied by high fever. The skin appeared almost entirely affected by roundish, sharp, erythematous lesions, some of these with evident ‘coccard’ sign, other ecchymotic with hemorrhagic nuance, confluent to the trunk in large patches. No recent history of infections or drugs. Laboratory findings showed a neutrophilia (N 8810/mcl) and eosinophilia (E 980/mcl) and high inflammatory indices (PCR 4.75 mg/dl, ferritin 517 kg/ml). Peripheral smear, autoimmunity, virological and bacterial screening and instrumental examinations were negative. On the third day of admission, he performed a nasal swab (Multiplex) due to the appearance of rhinorrhea and cough. It was positive for Human Metapenumovirus (HM). On the seventh day, there was a new poussé of erythematous, itchy, coccard element on the whole body surface. He was treated with antihistaminic, steroid and antibiotic therapy with gradual rash regression, desquamation of skin lesions and defervescence. In literature it is known that HM is a common cause of upper respiratory tract infection in children. However, no further cases are reported regarding the possible relationship between skin lesions and HM. In our case the only laboratory finding associate to the EM was a positive RT-PCR for HM. This observation could lead to further scientific evaluations

Spectrum of autoimmunity in celiac disease

The paper discusses the spectrum of autoimmunity in children with celiac diseas

Imerslund-GrÄsbeck syndrome and celiac disease: A strange but possible association

The paper describes the unusuala association of Imerslund-GrÄsbeck syndrome and celiac disease