Delayed Weight Gain Research Articles

Cichorium glandulosum Ameliorates HFD-Induced Obesity in Mice by Modulating Gut Microbiota and Bile Acids.

Obesity is an ongoing global health problem, and Cichorium glandulosum (CG, chicory) is traditionally used as a hepatoprotective and lipid-lowering drug. However, there is still a lack of research on the role of CG in the treatment of obesity. In the present study, we found that CG significantly delayed weight gain and positively affected glucolipid metabolism disorders, serum metabolism levels, and the degree of liver and kidney oxidative stress in high-fat diet (HFD) mice. Further examination of the effects of CG on intestinal microenvironmental dysregulation and its metabolites in HFD mice revealed that the CG ethanol extract high-dose group(CGH) did not have a significant regulatory effect on short-chain fatty acids. Still, CGH significantly decreased the levels of 12α-OH/non-12α-OH bile acids and also found significant upregulation of proteobacteria and downregulation of cyanobacteria at the phylum level. CG may have ameliorated obesity and metabolic abnormalities in mice by repairing gut microbiota dysbiosis and modulating bile acid biosynthesis.

Time-dependent changes in feeding behavior and energy balance associated with weight gain in mice fed obesogenic diets.

Obesity is characterized by dysregulated homeostatic mechanisms resulting in positive energy balance; however, when this dysregulation occurs is unknown. We assessed the time course of alterations to behaviors promoting weight gain in male and female mice switched to an obesogenic high-fat diet (HFD). Male and female C57BL/6J mice were housed in metabolic chambers and were switched from chow to a 60% or 45% HFD for 4 and 3 weeks, respectively. Food intake, meal patterns, energy expenditure (EE), and body weight were continuously measured. A separate cohort of male mice was switched from chow to a 60% HFD and was given access to locked or unlocked running wheels. Switching mice to obesogenic diets promotes transient bouts of hyperphagia during the first 2 weeks followed by persistent caloric hyperphagia. EE increases but not sufficiently enough to offset increased caloric intake, resulting in a sustained net positive energy balance. Hyperphagia is associated with consumption of calorically larger meals (impaired satiation) more frequently (impaired satiety), particularly during the light cycle. Running wheel exercise delays weight gain in male mice fed a 60% HFD by enhancing satiation and increasing EE. However, exercise effects on satiation are no longer apparent after 2 weeks, coinciding with weight gain. Exposure to obesogenic diets engages homeostatic regulatory mechanisms for ~2 weeks that ultimately fail, and consequent weight gain is characterized by impaired satiation and satiety. Insights into the etiology of obesity can be obtained by investigating changes to satiation and satiety mechanisms during the initial ~2 weeks of HFD exposure.

Allgrove Syndrome: A Case Report and Review of the Literature

Allgrove syndrome, or Triple A syndrome, is a very rare autosomal recessive disorder with three key clinical features: achalasia, alacrima, and adrenal insufficiency. Around a third of patients present with additional features, such as neurological and autonomic manifestations (making it syndrome 4A). Alacrima usually appears in early childhood, while achalasia and adrenal insufficiency manifest later. In adulthood, the presentation is predominantly neurological, with autonomic impairment and polyneuropathy. We report the case of a 7-year-old female patient who consulted us with delayed weight gain and nutritional issues, alacrimia, and chronic vomiting since the age of 6 months. Clinical examination revealed malnutrition, with weight and BMI less than 3 standard deviations. Alacrima was confirmed by a positive Schirmer's test. Oesogastroduodenal transit, gastric fibroscopy, and manometry confirmed achalasia. In our case, there was no neurological involvement nor adrenal insufficiency. Treatment consisted of optimal managing of the manifestations of the disease.

Nacc1 Mutation in Mice Models Rare Neurodevelopmental Disorder with Underlying Synaptic Dysfunction.

A missense mutation in the transcription repressor Nucleus accumbens-associated 1 (NACC1) gene at c.892C>T (p.Arg298Trp) on chromosome 19 causes severe neurodevelopmental delay ( Schoch et al., 2017). To model this disorder, we engineered the first mouse model with the homologous mutation (Nacc1+/R284W ) and examined mice from E17.5 to 8 months. Both genders had delayed weight gain, epileptiform discharges and altered power spectral distribution in cortical electroencephalogram, behavioral seizures, and marked hindlimb clasping; females displayed thigmotaxis in an open field. In the cortex, NACC1 long isoform, which harbors the mutation, increased from 3 to 6 months, whereas the short isoform, which is not present in humans and lacks aaR284 in mice, rose steadily from postnatal day (P) 7. Nuclear NACC1 immunoreactivity increased in cortical pyramidal neurons and parvalbumin containing interneurons but not in nuclei of astrocytes or oligodendroglia. Glial fibrillary acidic protein staining in astrocytic processes was diminished. RNA-seq of P14 mutant mice cortex revealed over 1,000 differentially expressed genes (DEGs). Glial transcripts were downregulated and synaptic genes upregulated. Top gene ontology terms from upregulated DEGs relate to postsynapse and ion channel function, while downregulated DEGs enriched for terms relating to metabolic function, mitochondria, and ribosomes. Levels of synaptic proteins were changed, but number and length of synaptic contacts were unaltered at 3 months. Homozygosity worsened some phenotypes including postnatal survival, weight gain delay, and increase in nuclear NACC1. This mouse model simulates a rare form of autism and will be indispensable for assessing pathophysiology and targets for therapeutic intervention.

Death receptor 5 is required for intestinal stem cell activity during intestinal epithelial renewal at homoeostasis

Intestinal epithelial renewal, which depends on the proliferation and differentiation of intestinal stem cells (ISCs), is essential for epithelial homoeostasis. Understanding the mechanism controlling ISC activity is important. We found that death receptor 5 (DR5) gene deletion (DR5-/-) mice had impaired epithelial absorption and barrier function, resulting in delayed weight gain, which might be related to the general reduction of differentiated epithelial cells. In DR5-/- mice, the expression of ISC marker genes, the number of Olfm4+ ISCs, and the number of Ki67+ and BrdU+ cells in crypt were reduced. Furthermore, DR5 deletion inhibited the expression of lineage differentiation genes driving ISC differentiation into enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Therefore, DR5 gene loss may inhibit the intestinal epithelial renewal by dampening ISC activity. The ability of crypts from DR5-/- mice to form organoids decreased, and selective DR5 activation by Bioymifi promoted organoid growth and the expression of ISC and intestinal epithelial cell marker genes. Silencing of endogenous DR5 ligand TRAIL in organoids down-regulated the expression of ISC and intestinal epithelial cell marker genes. So, DR5 expressed in intestinal crypts was involved in the regulation of ISC activity. DR5 deletion in vivo or activation in organoids inhibited or enhanced the activity of Wnt, Notch, and BMP signalling through regulating the production of Paneth cell-derived ISC niche factors. DR5 gene deletion caused apoptosis and DNA damage in transit amplifying cells by inhibiting ERK1/2 activity in intestinal crypts. Inhibition of ERK1/2 with PD0325901 dampened the ISC activity and epithelial regeneration. In organoids, when Bioymifi’s effect in activating ERK1/2 activity was completely blocked by PD0325901, its role in stimulating ISC activity and promoting epithelial regeneration was also eliminated. In summary, DR5 in intestinal crypts is essential for ISC activity during epithelial renewal under homoeostasis.

Cardiometabolic benefits of Lacticaseibacillus paracasei 8700:2: A randomized double-blind placebo-controlled trial

Modulating microbial metabolism via probiotic supplementation has been proposed as an attractive strategy for the prevention of cardiometabolic diseases. Recently, Lacticaseibacillus paracasei (L.paracasei) was reported to alleviate metabolic disorders in murine models, however, its beneficial effects in humans remain to be determined. This study evaluated whether L.paracasei supplementation could improve endothelial function and cardiometabolic health in subjects with metabolic syndrome (MetS). In this randomized, double-blind and placebo-controlled trial among 130 participants with MetS, subjects were randomly assigned to placebo or L.paracasei 8700: 2 (10 billion CFU) daily for 12 weeks. Endothelial function was measured by flow-mediated slowing, and cardiometabolic health was determined by both components and severity of MetS. Ideal compliance was defined as consumption no less than 70% of the capsules. 130 individuals (mean [SD] age, 45.97 [7.11] years; 95 men [73.1%]) were enrolled and randomized to L.paracasei (n=66) or placebo control (n=64). Compared to placebo, L.paracasei supplementation led to a greater reduction in remnant cholesterol (-0.16mmol/L, 95%CI:-0.29mmol/L to-0.02mmol/L; P=0.024). Such a reduction in remnant cholesterol was significantly associated with improvement in endothelial function (r=-0.23, P=0.027). In subjects with an ideal compliance with trial protocol, L.paracasei treatment additionally lowered triglycerides, alleviated MetS severity and delayed weight gain. On the contrary, no obvious effect on insulin sensitivity or pancreatic beta-cell function was observed after L.paracasei intervention. Moreover, regarding safety and tolerability, no significant between-group difference in protocol-specified adverse events of interest was observed. L.paracasei supplementation enhanced endothelial function potentially through downregulating remnant cholesterol levels. Our study provides a feasible and safe strategy for the prevention of cardiometabolic diseases in subjects with severe dyslipidemia and endothelial dysfunction. Under ClinicalTrails.gov identifier NCT05005754.

РЕЗУЛЬТАТЫ КАТАМНЕСТИЧЕСКОГО НАБЛЮДЕНИЯ И ОСОБЕННОСТИ ТЕЧЕНИЯ COVID-19 У ПАЦИЕНТОВ С НЕЙРОЭНДОКРИННОЙ КЛЕТОЧНОЙ ГИПЕРПЛАЗИЕЙ МЛАДЕНЦЕВ

Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare interstitial lung disease in children. The clinical features of the disease are characterized by tachypnea, moist rales/crepitus, retraction of compliant chest areas and delayed weight gain. The disease is diagnosed using the NEHI clinical scale coupled with the computed tomography of the chest organs. The clinical manifestations of NEHI regress as the child grows, but may persist up to the age of 10 y/o. The purpose of the research was to characterize the course of NEHI including the features of COVID-19 and the impact of passive smoking in children below the age of 8 y/o. Materials and methods: a single-center longitudinal study with follow-up observation of 29 patients with NEHI in January 2012 - December 2022 aged 8 months to 8 years old, 21 of which had COVID-19. Results: 20 of 29 patients with a known follow-up have undergone the long-term oxygen therapy (LTOT) at home lasting from 2 weeks up to 5.5 years (Me 1 year and 2 months; IQR 6 months - 4.5 years). Bronchial asthma was diagnosed in 2. 8 (28%) were diagnosed with atopic dermatitis, 6 (21%) with mental retardation, 3 (10%) with acute urticaria, and 2 (7%) with allergic rhinitis. Gastroesophageal reflux disease (GERD) was diagnosed in 7, all requiring LTOT. The frequency of episodes of respiratory infection was maximum in the first 2 years of life, amounting to 16 episodes per 2 years (Me 7; IQR 4 to 10), and the maximum frequency of hospitalizations during this age period was 5 (Me 2; IQR 1 to 2). Children-passive smokers were diagnosed with malnutrition more often (75%, p=0.449) and required LTOT more often (75%, p=0.694), were more often hospitalized (42%, p=0.422). Despite the possible need for LTOT patients with NEHI had COVID-19 in the form of nasopharyngitis in the majority of cases (89%). Only 8 out of 14 patients had symptoms of NEHI after 5 years of age, and only 1 out of 5 after 7 years. Malnutrition (body mass index for the age<-2) in the first year of life was diagnosed in 13 (45%) children. Malnutrition persisted in 9 out of 24 (37%) by the second year of life, in 5 out of 19 (26%) by the third year, and in 2 out of 14 (14%) by the fourth year of life. Not a single child died. Conclusion: the course of NEHI is characterized by the absence of lethal outcomes, frequent respiratory infections that led to hospitalizations in the first 2 years of life, mild course of COVID-19, regression of clinical symptoms and malnutrition as the child grows, comorbidity with atopic diseases and GERD. The priority should be given to the prevention of passive smoking in children with NEHI.

The maturation of exploratory behavior in adolescent Mus spicilegus on two photoperiods.

Dispersal from the natal site or familial group is a core milestone of adolescent development in many species. A wild species of mouse, Mus spicilegus, presents an exciting model in which to study adolescent development and dispersal because it shows different life history trajectory depending on season of birth. M. spicilegus born in spring and summer on long days (LD) disperse in the first 3 months of life, while M. spicilegus born on shorter autumnal days (SD) delay dispersal through the wintertime. We were interested in using these mice in a laboratory context to compare age-matched mice with differential motivation to disperse. To first test if we could find a proxy for dispersal related behavior in the laboratory environment, we measured open field and novel object investigation across development in M. spicilegus raised on a LD 12 h:12 h light:dark cycle. We found that between the first and second month of life, distance traveled and time in center of the open field increased significantly with age in M. spicilegus. Robust novel object investigation was observed in all age groups and decreased between the 2nd and 3rd month of life in LD males. Compared to male C57BL/6 mice, male M. spicilegus traveled significantly longer distances in the open field but spent less time in the center of the field. However, when a novel object was placed in the center of the open field, Male M. spicilegus, were significantly more willing to contact and mount it. To test if autumnal photoperiod affects exploratory behavior in M. spicilegus in a laboratory environment, we reared a cohort of M. spicilegus on a SD 10 h:14 h photoperiod and tested their exploratory behavior at P60-70. At this timepoint, we found SD rearing had no effect on open field metrics, but led to reduced novel object investigation. We also observed that in P60-70 males, SD reared M. spicilegus weighed less than LD reared M. spicilegus. These observations establish that SD photoperiod can delay weight gain and blunt some, but not all forms of exploratory behavior in adolescent M. spicilegus.

Protective effects of silymarin in broiler feed contaminated by mycotoxins: growth performance, meat antioxidant status, and fatty acid profiles.

The aim of this study was to determine whether the inclusion of silymarin in broiler feed was able to mitigate the adverse effects of mycotoxin on growth performance, health status, liver oxidative stress, and meat fatty acid profiles. A completely randomized design with four treatments, four repetitions, and 15 chicks per repetition was used, with the following groups: (a) feed without additives (NoMyc-NoSil), (b) feed supplemented with silymarin (NoMyc-Sil), (c) feed contaminated with mycotoxin (Myc-NoSil), and (d) feed contaminated with mycotoxin and supplemented with silymarin (Myc-Sil). Growth performance, intestinal and liver health, and meat quality were assessed. The consumption of feed contaminated with mycotoxin delayed weight gain and increased the feed conversion ratio; however, the addition of silymarin prevented these adverse effects on the chicken industry. Serum ALT activity was higher in Myc-NoSil broilers than in other groups. Intake of silymarin in healthy birds increased serum globulin concentration and reduced albumin concentration and ALT and AST serum activities compared to the Myc-NoSil group. The NoMyc-Sil birds had greater villus heights and crypt depths. Luminosity and water loss by cooking were affected by mycotoxin ingestion, changes that did not occur in the meat of birds that were supplemented with silymarin. The sum of saturated and monounsaturated fatty acids in the meat did not change among treatments, unlike the sum of polyunsaturated fatty acids higher in the meat of birds that consumed silymarin. We conclude that silymarin is a potential additive in broiler feed; it reduces impairment of growth performance at the end of the productive cycle, prevents oxidative stress, improves meat quality, and increases polyunsaturated fatty acids.

Serglycin-Deficiency Causes Reduced Weight Gain and Changed Intestinal Cytokine Responses in Mice Infected With Giardia intestinalis.

The proteoglycan serglycin (SG) is expressed by different innate and adaptive immune cells, e.g. mast cells, macrophages, neutrophils, and cytotoxic T lymphocytes, where SG contributes to correct granule storage and extracellular activity of inflammatory mediators. Here the serglycin-deficient (SG−/−) mouse strain was used to investigate the impact of SG on intestinal immune responses during infection with the non-invasive protozoan parasite Giardia intestinalis. Young (≈11 weeks old) oral gavage-infected congenic SG−/− mice showed reduced weight gain as compared with the infected SG+/+ littermate mice and the PBS-challenged SG−/− and SG+/+ littermate mice. The infection caused no major morphological changes in the small intestine. However, a SG-independent increased goblet cell and granulocyte cell count was observed, which did not correlate with an increased myeloperoxidase or neutrophil elastase activity. Furthermore, infected mice showed increased serum IL-6 levels, with significantly reduced serum IL-6 levels in infected SG-deficient mice and decreased intestinal expression levels of IL-6 in the infected SG-deficient mice. In infected mice the qPCR analysis of alarmins, chemokines, cytokines, and nitric oxide synthases (NOS), showed that the SG-deficiency caused reduced intestinal expression levels of TNF-α and CXCL2, and increased IFN-γ, CXCL1, and NOS1 levels as compared with SG-competent mice. This study shows that SG plays a regulatory role in intestinal immune responses, reflected by changes in chemokine and cytokine expression levels and a delayed weight gain in young SG−/− mice infected with G. intestinalis.

Effect of Different Types of Fat on Lipid Metabolism in Rats

The current study was conducted to inquiries and to determine the impact of different edible oils in experimental animals. Sixty albino rats that were randomly divided into 6 groups of 10 animals. The groups were fed on dietary without fat(control) (Group I), corn oil (Group II), butter fat (Group III), refined palm oil(Group IV) sunflower oil (Group V) and frying fat more than one for 8 weeks. After 12 h of diet removal, blood was collected to measure serum lipid profile (T.C., HDL, LDL and T.G.) levels. Rats of Group A were kept as control by feeding rat normal chow diet. Animals (rats) of groups B, C, D, E & F where fed by corn, butter, palm, sunflower and frying fat more than one oils respectively, at the dose of 15% in feed for 8 weeks. The procedures included determination of body weight gain, lipid profiles and histopathological lesions in different organs. All experimental rats declared advance or delay weight gain during the research period relying on type of oil. GC & GF oil treated group show highest significant (P<0.05) body weight gain, while GB, GD& gE show lowest significant (P<0.05, (P<0.05, P<0.03) Respectively than control group. Rats fed on diet include butterfat and frying more than one had the increment levels of TG, TC & LDL, and lower the HDL level than control group. On the other hand, corn, palm, sunflower oils led to the lower levels of TG, TC & LDL, but the same oils or viz (corn, palm, sunflower oils ) had incremented the HDL level as compare to control group.However, dietary intake of vegetable oils improved lipid profile, while butterfat and frying more than one had the contrary impact.

ПРИМЕНЕНИЕ ОПРОСНИКА ДЛЯ СКРИНИНГА СКРЫТЫХ ФОРМ АЛЛЕРГИИ НА БЕЛКИ КОРОВЬЕГО МОЛОКА У ДЕТЕЙ С ВОСПАЛИТЕЛЬНЫМИ ЗАБОЛЕВАНИЯМИ КИШЕЧНИКА

The role of food allergy (FA) in the development of clinical reactions to food in patients with inflammatory bowel disease (IBD) is being studied and remains highly controversial. However, it is obvious that for personalized therapy of this category of patients, it is necessary to consider all possible forms of food hypersensitivity. Objective of the research: to develop a questionnaire to identify latent forms of cow's milk protein allergy (CMPA) in children with IBD and to evaluate the effectiveness of its use. Materials and methods: 376 children were questioned: 176 children with IBD in remission and/or with a low degree of disease activity (1st group); 100 with confirmed CMPA (2nd group); 100 without FA manifestations (3rd group). Statistical analysis was performed using the SPSS (Statistical Package for the Social Sciences Inc., USA) version 26.0. Data analysis included standard descriptive and analytical statistics. Results: using a structured questionnaire for collecting anamnesis, it was found that the frequency of allergic reactions to food in the family history of children with IBD and in the group of patients with CMPA did not differ significantly. The introduction of dairy products into complementary foods earlier than at the age of 6 months in IBD patients was noted statistically significantly more often than in children with CMPA and children in the comparison group; the most significant difference was noted in patients with Crohn's disease (CD). In the early history, among children with IBD 83 (47,1%) had skin rashes, 121 (68,7%) regurgitation, 138 (78,4%) colic, 68 (38,6%) constipation. %), blood in stool – 53 (30,1%), mucus (in significant amounts) in stool – 70 (39,7%), loose stool – 77 (43,7%), delayed weight gain was noted in 25 (14,2%) children. At the same time, regurgitation and colic in children with IBD in the first year of life were noted statistically significantly more often than in children with CMPA and children in the comparison group. The frequency of symptoms such as blood and mucus in the stool, diarrhea and delayed weight gain in the first year of life did not statistically significantly differ in children with IBD and in the group of children with CMPA, but was significantly more frequent than in group 3. The median of the indicator according to the results of the questionnaire survey in children with CD was 57 points [52; 62], with ulcerative colitis (UC) – 54 points [50; 57], with PA – 61 points [58; 64], in the 3rd group – 10 points [8; 14]. At a threshold value (cutoff point) of 55 points, the sensitivity and specificity of the method were 79% and 74%, respectively. The area under the ROC curve, corresponding to the relationship between the presence of a subclinical form of allergy and the scores of the questionnaire, was 0,819±0,022 with 95% CI: 0,776–0,862. The resulting model was statistically significant (p<0,001). Conclusion: the questionnaire survey of children with IBD using a questionnaire aimed at identifying latent forms of FA allowed to reveal history peculiarities of children with IBD. The obtained indicators of questionnaire sensitivity and specificity allowed to use it in clinical practice as an additional screening method for detecting latent forms of CMPA in IBD patients with subsequent correction of nutritional support.

Clinical presentations, Laboratory analysis and Linear Growth in 50 Neonates and Young Infants with Acute Meningitis: One Year Experience of a Single Center in Qatar.

BackgroundMeningitis frequently occurs in neonates and can lead to a number of acute, severe complications and long-term disabilities. Although, long term growth delay and abnormal weight gain appear to be risk factors following an acute attack of both bacterial and aseptic meningitis in children, especially during the fast phase of infantile growth, the long-term effects of acute meningitis occurring during the neonatal and early infantile periods on linear growth (length, weight and head growth) have not fully reported.Aim of the studyThe objective of this study is to describe the clinical presentation of neonates and young infants with acute meningitis with different etiologies and to determine the clinical impact of the effect of acute meningitis on growth parameters.Material and methodsWe analyzed the clinical data and the growth parameters of 50 newborns and young infants (age: 1.6 ± 0.9 months) admitted to our hospital (Al Wakhra Hospital, Department of Pediatrics, Doha, Qatar), between 1-1-2016 to 1-1-2017, with acute meningitis. Anthropometric measurements included weight, length, and head circumference. Length SDS (L-SDS) and body-mass-index (BMI) were calculated and recorded at every clinic visit, every 3 months for 8 ± 2 months.ResultsIn this age group of neonates and young infants with acute meningitis fever (84%) and hypoactivity (64%) were the major presenting manifestations. Acute bacterial meningitis (n: 10) was associated with higher morbidity [shock (n: 1), subdural empyema (n: 1) and hydrocephalus (n: 1)]. Cerebrospinal fluid (CSF) examinations showed that infants with bacterial meningitis had significantly higher pleiocytosis of mainly polymorphic leukocytes and protein levels, compared to those with aseptic meningitis.All infants showed normal linear growth and weight gain during the follow-up period (8 ± 2 months). The annualized growth rate of infants was 25.3 ± 3.5 cm per year. All had normal length standard deviation scores (LSDS) (−0.2 ± 0.9) and none of them had LSDS < −2. All infants had a normal BMI (16.7 ± 1.8 kg/m2). Head circumference growth was normal in 49/50 infants (43.8 ± 1.8 cm) at 8 ± 2 months. One infant developed hydrocephalus after group B streptococcus (GBS) meningitis. There was no statistical difference in linear growth between infants with aseptic and bacterial meningitis.ConclusionAcute bacterial meningitis in newborns and young infants is still associated with considerably high morbidity and complications. Infantile linear growth appears to be normal in all newborns and young infants with both bacterial and aseptic meningitis.

Oral Acute and Repeated-Doses Toxicity Study of Valepotriates from Valeriana glechomifolia (Meyer) in Mice.

Species of Valeriana show sedative, hypnotic, anxiolytic, antidepressant and anti-inflammatory properties, which are associated with valepotriates. However, data about toxicity and safety of these compounds are still limited. The aim of this study was to investigate the toxicity of a valepotriate-enriched fraction (VAL) from Valeriana glechomifolia Meyer based on the Organization for Economic Cooperation and Development (OECD) guidelines 423 and 407. In the acute study, CF1 mice were treated with a single dose of VAL (2000 mg/kg, p.o.) and observed for 14 days. In the repeated dose study, CF1 mice received single daily doses of VAL (30, 150 or 300 mg/kg, p.o.) or vehicle for 28 days. These doses were chosen based on previous results by our group and according to Guideline 407- OECD. The acute study allowed to classify VAL in the hazard category 5. The repeat-dose study has shown that VAL 300 mg/kg delayed weight gain and reduced food consumption in the first week, probably due to transient sedative effects. The other doses had no effect on animals' ponderal evolution. At the end of the treatment, all groups had equal body weight and food consumption. None of the doses altered any behavioral, urinary, biochemical, hematological, anatomic or histological parameters. A valepotriate-enriched fraction from Valeriana glechomifolia presents relatively low oral acute toxicity and does not induce evident toxicity after oral repeated treatment (at least up to 300 mg/kg) in mice.

Proteomic pattern of breast milk discriminates obese mothers with infants of delayed weight gain from normal-weight mothers with infants of normal weight gain.

We previously reported that exclusively breastfed infants born to mothers with pregestational obesity gain less weight during the first month after birth than those born to mothers of normal pregestational weight. This issue is potentially important since lower weight gain in breastfed infants of obese mothers might increase the risk of developing later obesity. Breast milk quality and quantity, together with breastfeeding practice, possibly influence infants’ feeding behavior, appetite control, and regulation of growth later in life. The issue of whether breast milk protein patterns from obese mothers differ in composition from those of non‐obese mothers remains largely unexplored. Here, we established a breast milk proteomic pattern that discriminates obese mothers and infants with delayed weight gain at 1 month after birth from normal‐weight mothers with infants of the same age and with normal weight gain. Obese mothers were matched to normal‐weight mothers (n = 26; body mass index 33.5 ± 3.2 vs 21.5 ± 1.5 kg·m−2). The mean weight gain of infants in the obese group at 1 month after birth was 430.8 g lower than that of the infants in the control group. Analysis of the breast milk delipidized fraction by surface‐enhanced laser desorption/ionization on CM10 and Q10 arrays was followed by MS‐assisted purification and LC‐MS/MS microsequencing of a selected biomarker. We identified 15 candidate protein biomarkers, seven of which were overexpressed in the obese group and eight in the normal‐weight group. One of the most significant candidate biomarkers, overexpressed in the obese group, was identified as a fragment of the sixth extracellular domain of the polymeric immunoglobulin receptor. Further structural identification of these candidate biomarkers and their validation in clinical assays may facilitate the development of a predictive immunoassay.

Acupuncture at ST36 exerts neuroprotective effects via inhibition of reactive astrogliosis in infantile rats with hydrocephalus

BackgroundAcupuncture has been associated with improved cerebral circulation, analgesia, neuromodulatory function and neurogenesis. In particular, acupuncture at ST36 has been widely used in several central nervous system (CNS) disorders, including...

The adaptor molecule Trif contributes to murine host defense during Leptospiral infection

Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon β (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif−/− mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif−/− mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans.

A twin sibling with Prader-Willi syndrome caused by type 2 microdeletion following assisted reproductive technology: A case report.

Prader-Willi syndrome (PWS) is a neurobehavioral imprinting disorder, which arises due to an absence of paternally expressed genes within the 15q11.2-q13 region. This occurs via one of the three main genetic mechanisms, as follows: Deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. Recent studies have reported an association between imprinting disorders and assisted reproductive technologies (ART). The current study presents a 6-year-old female patient who is a dizygotic twin, in which one was born with de novo microdeletion at 15q11.2-q13.1 following in vitro fertilization. The patient had characteristic facial features including narrow bifrontal diameter, strabismus, downturned mouth, feeding problems and generalized hypotonia during infancy, developmental delay, mental retardation and rapid weight gain. Based upon phenotypic resemblance and the medical records, methylation-specific multiplex ligation-dependent probe amplification and array-based comparative genome hybridization analyses demonstrate type 2 microdeletion between breaking point 2 (BP2) and BP3, which occur from MKRN3 through HERC2 at 15q11.2-q13.1. To the best of our knowledge, the present study is the first to report a PWS case born following ART reported in South Korea. In addition to previous studies, the present study contributes to the consensus regarding genotype-phenotype comparisons in this respect.

The prevalence of bronchial asthma among primary school children in Menoufiya Governorate (El-Bagour Center)

Objective To study the prevalence of bronchial asthma among primary school children in Menoufiya Governorate (El-Bagour Center). Background Asthma is a common disease in children that forms a major comorbidity illness. It is prevalent worldwide, especially in developed countries where its prevalence is increasing to epidemic proportions. Patients and Methods This is an observational study carried out on 2544 children from a representative sample of children attending eight primary schools in El-Menoufiya Governorate (El-Bagour Center): four schools were located inside El-Bagour Center, representing the urban locality, and the other four schools were located in villages around El-Bagour Center, representing the rural locality. Children were screened for chest symptoms by a questionnaire. Results The prevalence of asthma in rural and urban schools was 5.34 and 6.58%, respectively, with a total prevalence of 6.09%. A low socioeconomic level, a positive family history of similar disease, and exposure to smoke showed a highly significant effect as risk factors for asthma. Bronchial asthma had a highly significant effect on delayed weight gain, disturbed sleep, missed school days, limited activity, and emergency room visits and had a significant effect on delayed growth. Conclusion The overall point prevalence of childhood bronchial asthma among primary school children in Menoufiya governorate was 6.5%, which reflects a significant increase over the last 20 years when compared with a previous prevalence rate of 2.2% in a similar study conducted more than 20 years ago. This reveals a significant increase in the magnitude of the problem of bronchial asthma in our community and the need for effective prevention and management programs.

Safety study of Ciprofloxacin in newborn mice

Ciprofloxacin, a broad-spectrum antimicrobial agent belonging to the fluoroquinolone family, is prescribed off-label in infants less than one year of age. Ciprofloxacin is included in the European Medicines Agency priority list of off-patent medicinal products requiring evaluation in neonates. This evaluation is undergoing within the TINN (Treat Infections in Neonates) FP7 EU project. As part of the TINN project, the present preclinical study was designed to assess the potential adverse effects of Ciprofloxacin on neurodevelopment, liver and joints in mice. Newborn mice received subcutaneous Ciprofloxacin at 10, 30 and 100 mg/kg/day from 2 to 12 postnatal days. Peak plasma levels of Ciprofloxacin were in the range of levels measured in human neonates. We examined vital functions in vivo, including cardiorespiratory parameters and temperature, psychomotor development, exploratory behavior, arthro-, nephro- and hepato-toxic effects. We found no effect of Ciprofloxacin at 10 and 30 mg/kg/day. In contrast, administration at 100 mg/kg/day delayed weight gain, impaired cardiorespiratory and psychomotor development, caused inflammatory infiltrates in the connective tissues surrounding the knee joint, and moderately increased extramedullary hematopoiesis. The present study pleads for careful watching of cardiorespiratory and motor development in neonates treated with Ciprofloxacin, in addition to the standard surveillance of arthrotoxicity.