Slow Weight Gain Research Articles

Food Insecurity and Weight Faltering: US Multisite Analysis of Young Children’s Weight Trajectory

BackgroundFood insecurity is associated with poor health and development among young children, with inconsistent findings related to longitudinal growth. ObjectiveTo investigate associations between household and child food insecurity and young children’s weight trajectory during ages 0-2 years. DesignLongitudinal survey data were analyzed for years 2009-2018. Participants/SettingRacially diverse mothers of 814 children ≤24 months interviewed twice (interval >6 months, mean 11 months) in emergency departments of 4 US cities. Children were included if born at term, with birthweight within 2500g-4500g, weight-for-age z-score (WAZ) within ±2 SD at first interview. Main outcome measuresWAZ difference between 2 visits was defined as ‘expected weight gain’ (within ±1.34 SD), ‘slow weight gain’ (<-1.34 SD), or ‘rapid weight gain’ (>+1.34 SD). Statistical analyses performedMultinomial logistic regression was conducted to examine adjusted associations between household or child food insecurity and WAZ differences. ResultsOf 814 children, 83.5% had expected, 7% slow, and 9.5% rapid weight gain, with mean of 11 months (SD ±4) between visits. Child food insecurity, but not household food insecurity, was associated with slow weight gain (aRRR 2.44 [95% CI 1.16-5.13]; aRRR 1.30; [95% CI 0.69-2.51], respectively). Neither exposure was associated with rapid weight gain. ConclusionsThe association between child food insecurity and slow weight gain during the first two years of life raises clinical concern. Tracking child food insecurity in addition to household food insecurity can be an effective strategy to prevent weight faltering and to support optimal child growth.

Association between Slow and Rapid Weight Gain before 36 Weeks of Corrected Age and 6-Year-Developmental Quotient in Infants Born at

The postnatal growth of preterm infants is influenced by various factors; however, the association between growth and long-term outcomes in extremely preterm infants remains unclear. Therefore, we aimed to determine the association between 6-year development and body weight (BW) at 36 weeks of corrected age (CA) in extremely preterm infants. We conducted a retrospective observational study including extremely preterm infants born at < 26 weeks of gestation. We defined the key standard deviation score (SDS) using BW at birth and evaluated the association between BW-related values at 36 weeks of CA and the 6-year developmental quotient (DQ). This study included 90 infants. The absolute difference between changes in the BW SDS from birth and the median changes in DQ ≥ 85 infants was significantly greater in infants with a DQ < 85 than ≥85 (median [interquartile range]: 0.80 [0.29, 1.31] vs. 0.34 [0.13, 0.55]; p = 0.001). After adjustment by the logistic regression analysis for DQ < 85, the absolute difference was statistically significant (odds ratio: 4.99, 95% confidence interval: 1.71-14.5). The correlation coefficient between the absolute difference and DQ was -0.35 (p < 0.001). There were no significant associations between a DQ < 85 and SDS or changes in SDS from birth. For infants born at <26 weeks of gestation, slow and rapid weight gain were associated with a low 6-year DQ when using values representing individual body sizes at birth. Individual backgrounds should be considered to avoid both slow and rapid weight gain for the growth management of these infants for at least up to 36 weeks of CA. Further research is needed to determine which body size has a positive impact on the long-term outcomes of infants. · The median change in BW SDS was a key factor for DQ.. · Slow/rapid weight gain were related to a low 6-year DQ.. · Individual backgrounds may be important in neonatal intensive care unit care..

Penguatan Pengetahuan Nutrisi Lokal untuk Pemberian MPASI dalam Pencegahan Faltering Growth pada Balita

Faltering growth is characterized by slow weight gain in early childhood, often the root cause of stunting in developing countries. In Indonesia, the stunting rate in toddlers reaches 24%, with high prevalence also recorded in West Nusa Tenggara (NTB). The leading causes of stunted growth include inadequate nutritional intake and infection, which impact children's physical and cognitive development. Early intervention through nutrition education is essential to prevent long-term impacts. Through education and leaflet media, this community service program aims to improve mothers' knowledge about locally-based MPASI at the Pringgarata Health Center. This program takes place in three stages—preparation, implementation, and evaluation—with 20 participants consisting of mothers and community leaders. The evaluation results showed a significant increase in mothers' knowledge from 30% to 85% after education, stating that this approach effectively improves understanding and potentially prevents faltering growth.

Chronic metabolic effects of novel gut-oriented small-molecule GPR119 agonists in diet-induced obese mice

The pharmacological activation of G-protein coupled receptor-119 (GPR119) modulates glucose, energy, and hepatic lipid homeostasis in type-2 diabetes (T2D). We developed synthetic small-molecule GPR119 agonists targeting gastrointestinal receptors. This study investigates the chronic metabolic effects of lead candidates, ps297 and ps318, individually and in combination with sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, in high-fat diet (HFD)-induced obese (DIO) mice. In a 10-week dose-escalation protocol, DIO mice were orally treated with the investigational agents alone (10–90 mg/kg/day) and in combination with sitagliptin (20 mg/kg/day). Weekly body weight, food intake, and random blood glucose levels were monitored during the treatment phase. Post-treatment, an intraperitoneal glucose tolerance test (ipGTT), estimation of plasma biomarkers and haematological assessment were conducted. The treatment’s effect on hepatic steatosis was studied by estimating liver biomarkers and histological examinations. Ten-week sitagliptin combination therapy with the investigational entities restored incretins, insulin, and other metabolic hormonal secretions, accompanied by improved glucose homeostasis and retarded weight gain. Interestingly, monotherapy with investigational agents improved liver health by reducing liver weight, liver enzymes, and inflammation. Hepatic effects were further enhanced by co-administration of sitagliptin, evident by amelioration in hepatic steatosis endpoints such as liver weight, plasma liver enzyme concentrations, hepatic triglycerides (TG), total cholesterol (CHO), hydroxyproline content, and cytokine levels. Histopathological investigations confirmed regression in hepatic steatosis in the combination groups. These findings demonstrate the therapeutic potential of novel gut-oriented GPR119 agonists in combination with a DPP-IV inhibitor to ameliorate metabolic dysfunction-associated steatohepatitis (MASH), warranting further mechanistic investigations.

The proportion of weight gain due to change in fat mass in infants with vs without rapid growth.

There is extensive evidence that rapid infant weight gain increases the risk of childhood obesity, but this is normally based on childhood body mass index (BMI) only and whether or not this is because infants with rapid weight gain accrue greater fat mass is unknown. The primary objective of our study was to test whether the proportion of infant weight gain due to concurrent increases in fat mass is greater in infants with rapid weight gain as compared to those with normal growth. Body composition was assessed by (1) air-displacement plethysmography (ADP) at 0 and 6 months in 342 infants from Australia, India, and South Africa and (2) deuterium dilution (DD) at 3 and 24 months in 555 infants from Brazil, Pakistan, South Africa, and Sri Lanka. Weight gain and length growth were each categorized as slow, normal, or rapid using cut-offs of <-0.67 or >+0.67 Z-scores. Regression was used to estimate and contrast the percentages of weight change due to fat mass change. Approximately 40% of the average weight gain between 0 and 6 months and 20% of the average weight gain between 3 and 24 months was due to increase in fat mass. In both samples, compared to the normal group, the proportion of weight gain due to fat mass was higher on average among infants with rapid weight gain and lower among infants with slow weight gain, with considerable individual variability. Conversely, slow and rapid length growth was not associated with differential gains in fat mass. Pediatricians should monitor infant growth with the understanding that, while crossing upward through the weight centiles generally is accompanied by greater adiposity gains (not just higher BMI), upward crossing through the length centiles is not.

Vaccination with a Lawsonia intracellularis subunit water in oil emulsion vaccine mitigated some disease parameters but failed to affect shedding

Lawsonia intracellularis is the causative agent of ileitis in swine that manifests as slower weight gain, mild or hemorrhagic diarrhea and/or death in severe cases. As an economically important swine pathogen, development of effective vaccines is important to the swine industry. In developing a subunit vaccine with three recombinant antigens - FliC, GroEL and YopN – we wanted to identify a formulation that would produce robust immune responses that reduce disease parameters associated with Lawsonia intracellularis infection. We formulated these three antigens with four adjuvants: Montanide ISA 660 VG, Montanide Gel 02 PR, Montanide IMS 1313 VG NST, and Montanide ISA 61 VG in an immunogenicity study. Groups vaccinated with formulations including Montanide ISA 660 VG or Montanide ISA 61 VG had significantly more robust immune responses than groups vaccinated with formulations including Montanide Gel 02 PR or Montanide IMS 1313 VG NST. In the challenge study, animals vaccinated with these antigens and Montanide ISA 61 VG had reduced lesion scores, reduced lesion lengths, and increased average daily gain, but no reduction in shedding relative to the control animals. This work shows that this vaccine formulation should be considered for future study in a field and performance trial.

Genomic and pathogenicity analysis of two novel highly pathogenic recombinant NADC30-like PRRSV strains in China, in 2023.

Porcine reproductive and respiratory syndrome viruses (PRRSVs) exhibit high mutability and recombination, posing challenges to their immunization and control. This study isolated two new PRRSV strains, GD-7 and GX-3, from samples collected in Guangdong and Guangxi in 2023. Whole-genome sequencing, along with phylogenetic and recombination analyses, confirmed that GD-7 and GX-3 are natural novel recombinant strains of NADC30 PRRSV. Moreover, we established a pathogenicity model for piglets and sows based on the two isolates. The results of piglet pathogenicity revealed that both GD-7 and GX-3 caused clinical symptoms such as fever, loss of appetite, depression, and slow weight gain. Moreover, we observed that the mortality rate of GD-7-inoculated group piglets was 33.3%, which was similar to that of piglets infected with other highly pathogenic PRRSV strains and exceeded the mortality rate of most NADC30-like PRRSV. In pregnant sow models, the survival rate of sows in the GD-7 group was 75%, in contrast to the GX-3 group, where no sow mortality was observed, and both strains resulted in abortion, mummified fetuses, and stillbirths. These results highlight the elevated pathogenicity of these recombinant strains in sows, with GD-7 mainly causing sows to abort, and GX-3 mainly causing sows to give birth to mummified fetuses. This study introduces two distinct clinical recombinant PRRSV strains that differ from the prevalent strains in China. This research furthers our understanding of the epidemiology of PRRSV and underscores the significance of ongoing monitoring and research in the face of evolving virus strains. Moreover, these discoveries act as early warnings, underscoring the necessity for active control and immunization against PRRSV.IMPORTANCESince the discovery of NADC30-like PRRSV in China in 2013, it has gradually become the dominant strain of PRRSV in China. NADC30-like PRRSV exhibits high recombination characteristics, constantly recombining with different strains, leading to the emergence of numerous novel strains. Of particular importance is the observation that NADC30-like PRRSV with different recombination patterns exhibits varying pathogenicity, which has a significant impact on the pig farming industry. This emphasizes the necessity of monitoring and responding to evolving PRRSV strains to develop effective immunization and control strategies. In this paper, we conducted pathogenicity studies on the isolated NADC30-like PRRSV and analyzed the differences in the genomes and pathogenicity of the different strains by recording clinical symptoms, temperature changes, detoxification tests, and changes in viremia and histopathology in infected pigs. This was done to provide a theoretical basis for the epidemiological situation and epidemic prevention and control of PRRSV.

Failure to Thrive, Metabolic Acidosis, and Diarrhea in a 7-Week-Old Infant.

A 7-week-old infant presented to the emergency department with fussiness, decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy.

Evaluate the results of anesthesia and resuscitation of minimally invasive surgery for pediatric patients with ventricular septal defect at Cardiovascular Center, E hospital in 2022

Objective: Minimally invasive surgery has recently been implemented safely and effectively on children. The study aimed to evaluate the results of anesthesia and resuscitation in pediatric patients with ventricular septal defects (VSD) undergoing minimally invasive surgery. Methods: A cross-sectional study from January 1, 2021 to June 30, 2022 on 65 patients underwent minimally invasive surgery to repair ventricular septal defect, at Cardiovascular Center, E Hospital. Result: A toltal of 65 children aged from 1 month to 34 months, mean weight of 9.0 ± 6.3kg, mean height of 73.6 ± 22.1cm, with main clinical symptoms of slow weight gain (62.5%) and grade I heart failure (87.7%). The most common VSD location was perimembranous VSD (67.7%) with an mean size of 5.7±2.6 mm. The mean surgical time was 175 minutes with cardiopulmonary bypass time and aortic cross-clamp time of 77.5 and 53.0 minutes, respectively. Postoperative hemodynamic parameters changed statistically significantly compared to pre-operation: blood pressure decreased, heart rate increased, lactate level increased, P/F ratio decreased, blood potassium level decreased. The patient mainly needed to use 1 vasopressor, 1 type of sedative analgesic, continuous diuresis, and prophylactic antibiotics with a vasopressor withdrawal time of 34.2 hours, a sedation withdrawal time of 13.35 hours, and a sedative withdrawal time of 13.35 hours. Intubation time of 20.8 hours (minimum 2 hours) and length of stay ICU was 3.8 days. Postoperative complications were low, mainly pneumonia (9.2%) and residual shunt (9.2%), and no death was observed. Conclusion: Minimally invasive ventricular septal defect surgery showed that the anesthesia and surgical process did not change much, with relatively fast post-operative recovery results, short medication time, quick recovery, and no recording severe complications.

Lacticaseibacillus rhamnosus Strains for Alleviation of Irritable Bowel Disease and Chronic Fatigue Syndrome.

Lacticaseibacillus rhamnosus is applied as a probiotic to alleviate various metabolic, gastrointestinal, and psychological symptoms and diseases, and its probiotic effectiveness is strain-specific. In this study, we obtained 21 strains of Ls. rhamnosus, and their genomes were sequenced. We defined the pan- and core-genomes of Ls. rhamnosus. Phenotypes such as the assimilation of carbohydrates and antibiotic resistance were experimentally characterized and associated with genome annotations. Nine strains were selected and tested for growth rates, tolerance to acidity/alkalinity and bile acids, the production of short-chain fatty acids, and competition with pathogenic microbes. Strains WL11 and WL17 were targeted as potential probiotics and were applied in mouse model tests for the alleviation of chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS). The results showed that WL11 and WL17 effectively alleviated slow body weight gain, anxiety, poor memory, and cognitive impairment in CFS mouse models. They also reduced the expression of pro-inflammatory factors, such as TNF-α and IL-6, and alleviated intestinal peristalsis, visceral hypersensitivity, and anxiety-like behavior in IBS mouse models. This study reports new Ls. rhamnosus strain resources and their effect on alleviation of both IBS and CFS symptoms with mouse models; the probiotic functions of those strains in human patients remain to be further tested.

Anti-obesity effects of potential probiotic Lactobacillus strains isolated from Mongolian fermented dairy products in high-fat diet-induced obese rodent model.

This study aims to investigate the anti-obesity properties of lactic acid bacteria (LAB) isolated from fermented dairy products such as "Airag" and "Khoormog" in Mongolia. These traditional dairy products are widely used in Mongolia and believe in having potential probiotic, anti-diabetes, anti-cancer, and anti-tuberculosis properties and are made from unheated two-humped camel milk and mare milk, respectively. We chose three LAB strains based on their probiotic characteristics, including tolerance of gastric and bile acids. Then we checked the anti-obesity activity of probiotic strains in vivo. An animal model was evaluated in twenty male C57BL/6J mice by inducing obesity with a high-fat diet (HFD), which was divided into five groups: regular diet group (Negative control), HFD group (Positive control), HFD with Lacticaseibacillus paracasei X-1 (X-1), Lacticaseibacillus paracasei X-17 (X-17), and Limosilactobacillus fermentum BM-325 (BM-325). For six weeks, 5 × 109 colony-forming units (CFU) of bacteria were given orally to the LAB-fed groups. Fasting blood glucose (FBG), lipid profiles, organ index, and organ morphology were all measured. The probiotic strains suppressed growth in adipose cell volume, stabilized FBG, reduced liver cell degeneration, and slowed HFD-induced body weight gain. The results suggest that some strains increase general metabolism while lowering body weight.

Effects of electroacupuncture with "intestinal disease prescription" on NLRP3 inflammasome and intestinal mucosal barrier in rats with acute ulcerative colitis.

To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC. Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1β) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence. Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (P<0.01), increased DAI score and spleen index (P<0.01), elevated serum IL-18 and IL-1β levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (P<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (P<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (P<0.05), reduced DAI scores and spleen indexes (P<0.05), decreased serum IL-18 and IL-1β levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (P<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (P<0.05). There were no significant differences in the above indexes between the medication group and the EA group (P>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration. EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.

The Inhibitory Effect of Early Pregnancy Factor on Red Meat Neu5Gc-Mediated Antibody Production in CMAH-/- Mice.

The meat derived from mammals such as cows, sheep, and pigs is commonly referred to as red meat. Recent studies have shown that consuming red meat can activate the immune system, produce antibodies, and subsequently develop into tumors and cancer. This is due to the presence of a potential carcinogenic compound in red meat called N-ethanol neuraminic acid (Neu5Gc). Neu5Gc is a common sialic monosaccharide in mammals, synthesized from N-acetylneuraminic acid (Neu5Ac) in the body and typically present in most mammals. However, due to the lack of the CMAH gene encoding the cytidine 5'-monophosphate Neu5Ac hydroxylase, humans are unable to synthesize Neu5Gc. Compared to primates such as mice or chimpanzees, the specific loss of Neu5Gc expression in humans is attributed to fixed genome mutations in CMAH. Although Neu5Gc cannot be produced, it can be introduced from specific dietary sources such as red meat and milk, so it is necessary to use mice or chimpanzees that knock out the CMAH gene instead of humans as experimental models. Further research has shown that early pregnancy factor (EPF) has the ability to regulate CD4+T cell-dependent immune responses. In this study, we established a simulated human animal model using C57/BL6 mice with CMAH gene knockout and analyzed the inhibitory effect of EPF on red meat Neu5Gc-induced CMAH-/- C57/BL6 mouse antibody production and chronic inflammation development. The results showed that the intervention of EPF reduced slow weight gain and shortened colon length in mice. In addition, EPF treatment significantly reduced the levels of anti Neu5Gc antibodies in the body, as well as the inflammatory factors IL-6 and IL-1β, TNF-α and the activity of MPO. In addition, it also alleviated damage to liver and intestinal tissues and reduced the content of CD4 cells and the expression of B cell activation molecules CD80 and CD86 in mice. In summary, EPF effectively inhibited Neu5Gc-induced antibody production, reduced inflammation levels in mice, and alleviated Neu5Gc-induced inflammation. This will provide a new re-search concept and potential approach for developing immunosuppressants to address safety issues related to long-term consumption of red meat.

Epidemiological investigation of coccidiosis and associated risk factors in broiler chickens immunized with live anticoccidial vaccines in China.

Coccidiosis is a costly intestinal disease of chickens caused by Eimeria species. This infection is associated with high mortality, reduced feed efficiency, and slowed body weight gain. The diagnosis and control of coccidiosis becomes challenging due to the fact that chickens can be infected by seven different Eimeria species and often occur mixed-species co-infections. Grasping the epidemiology of Eimeria species is crucial to estimate the efficiency of poultry management. This study aimed to explore the distribution of Eimeria species in broiler chickens in China after administering live anticoccidial vaccines. A total of 634 samples were obtained, and the survey results showed that the prevalence of Eimeria was 86.12% (546/634), and the most common species were E. acervulina (65.62%), E. necatrix (50.95%), E. mitis (50.79%), E. tenella (48.42%), and E. praecox (41.80%). Most samples indicated mixed-species infections (an average of 3.29 species per positive sample). Notably, 63.98% of samples contain 3 to 5 Eimeria species within a single fecal sample. The most prevalent combinations were E. acervulina-E. tenella (38.96%) and E. acervulina-E. necatrix (37.22%). Statistical analysis showed that flocks vaccinated with trivalent vaccines were significantly positive for E. necatrix in grower chickens (OR = 3.30, p < 0.05) compared with starter chickens, and tetravalent vaccinated flocks showed that starter chickens demonstrated a higher susceptibility to E. tenella-E. brunetti (OR = 2.03, p < 0.05) and E. acervulina-E. maxima (OR = 2.05, p < 0.05) compared with adult chickens. Geographically, in the case of tetravalent vaccine-immunized flocks, a substantial positive association was observed between E. necatrix infection rates and flocks from eastern (OR = 3.88, p < 0.001), central (OR = 2.65, p = 0.001), and southern China (OR = 3.17, p < 0.001) compared with southwestern China. This study also found a positive association between E. necatrix (OR = 1.64, p < 0.05), E. acervulina (OR = 1.59, p < 0.05), and E. praecox (OR = 1.81, p < 0.05) infection and coccidiosis occurrence compared with non-infected flocks in tetravalent vaccinated flocks. This molecular epidemiological investigation showed a high prevalence of Eimeria species in the field. The emergent species, E. brunetti and E. praecox, might be incorporated into the widely-used live vaccines in the future. These insights could be useful in refining coccidiosis control strategies in the poultry industry.

Altered metabolome and microbiome associated with compromised intestinal barrier induced hepatic lipid metabolic disorder in mice after subacute and subchronic ozone exposure

Exposure to ozone has been associated with metabolic disorders in humans, but the underlying mechanism remains unclear. In this study, the role of the gut-liver axis and the potential mechanism behind the metabolic disorder were investigated by histological examination, microbiome and metabolome approaches in mice during the subacute (4-week) and subchronic (12-week) exposure to 0.5 ppm and 2.5 ppm ozone. Ozone exposure resulted in slowed weight gain and reduced hepatic lipid contents in a dose-dependent manner. After exposure to ozone, the number of intestinal goblet cells decreased, while the number of tuft cells increased. Tight junction protein zonula occludens-1 (ZO-1) was significantly downregulated, and the apoptosis of epithelial cells increased with compensatory proliferation, indicating a compromised chemical and physical layer of the intestinal barrier. The hepatic and cecal metabolic profiles were altered, primarily related to lipid metabolism and oxidative stress. The abundance of Muribaculaceae increased dose-dependently in both colon and cecum, and was associated with the decrease of metabolites such as bile acids, betaine, and L-carnitine, which subsequently disrupted the intestinal barrier and lipid metabolism. Overall, this study found that subacute and subchronic exposure to ozone induced metabolic disorder via disturbing the gut-liver axis, especially the intestinal barrier. These findings provide new mechanistic understanding of the health risks associated with environmental ozone exposure and other oxidative stressors.

Ghrelin Alleviates Inflammation, Insulin Resistance, and Reproductive Abnormalities in Mice with Polycystic Ovary Syndrome via the TLR4-NF-κB Signaling Pathway.

Polycystic ovary syndrome (PCOS) commonly impacts fertile females with potentially severe effects on fertility and metabolism. Blood ghrelin levels are lower in PCOS patients, and exogenous supplements have been proposed for their potential to trigger anti-inflammatory effects at the cellular level. This study aimed to investigate whether pretreatment with ghrelin reduced inflammation, insulin resistance, and reproductive abnormalities in PCOS and the underlying mechanism of this disorder. Ghrelin supplementation was first tested in an inflammation model using human ovarian granulosa cells (KGN cells) that were built by treated with Lipolyaccharide. KGN cells were pretreated with ghrelin and exposed to lipopolysaccharide (LPS). Inflammatory gene expression and cytokine production were analyzed by Enzyme-linked immunosorbent assay (ELISA). Based on these results, the PCOS mice model was built with Dehydroepiandrosterone (DHEA) and a high-fat diet. The mRNA and protein expressions of inflammatory factors including Toll-like receptor 4 (TLR4), nuclear factor kappa-B-p65 (NF-κB-p65), Phospho-NF-κB-p65 (p-NF-κB-p65) and myeloid differentiation factor 88 (MYD88) related to the TLR4/NF-κB signaling pathway were evaluated in KGN cells and mouse ovarian tissues using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. Lipid metabolism was quantified via an automated biochemical analyzer. The mRNA and protein expressions of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in ghrelin pretreated KGN cells were lower than the LPS group (p < 0.05). Protein expression was reduced for TLR4, NF-κB-p65, and MYD88 within KGN cells of ghrelin groups compared to the LPS group (p < 0.05). Ghrelin treatment restored the estrous cycle and slowed weight gain and abdominal fat weight of PCOS mice (p < 0.05). Ghrelin treatment decreased the serum concentrations of testosterone, luteinizing hormone, insulin, IL-6, IL-1β, and TNF-α compared to the PCOS group (p < 0.05). Estradiol concentrations of mice treated with ghrelin were higher than the PCOS group (p < 0.05). The concentrations of low and high-density lipoprotein, triglyceride, and cholesterol in mice treated with ghrelin were lower than in the PCOS mice (p < 0.05). Inflammatory gene expression for IL-6, IL-1β, TNF-α, TLR4, NF-κB-p65, and MYD88 decreased in the ovarian tissues of ghrelin-treated mice compared to the PCOS group (p < 0.05), along with reduced protein expression of TLR4, p-NF-κB-p65, and MYD88 (p < 0.05). In the present study, ghrelin treatment effectively reduced inflammation in vitro, and attenuated insulin resistance and reproductive abnormalities in PCOS mice through the TLR4/NF-κB signaling pathway, highlighting potential therapeutic avenues for future PCOS treatments and research directions.

THE PATTERN OF SILVER-RUSSELL SYNDROME: OWN OBSERVATION

Silver-Russell syndrome (SRS) –is an orphan disease characterized by intrauterine and postnatal growth retardation. Children have special phenotypes, difficulties in feeding, the threat of insulin resistance, hypoglycemia, and accelerated sexual development. Aim: Increasing the effectiveness of SRS diagnosis based on the study of the features of the clinical and genetic course. Material and Methods: Clinical examination, blood tests, biochemistry, genetic tests, polymer chain reactions, and ultrasound examination have been carried out. Results: The child, 5 years old, was born from 2nd full-term pregnancy at 37 weeks, 2nd cesarean delivery with a body weight of 1900 g, height of 46 cm, head circumference of 30 cm, and chest circumference of 27 cm. Apgar scored 6/7 points. Neonatal adaptation disorders, intrauterine development, symmetrical shape, risk of hemolytic disease of the newborn according to the Rhesus factor (total bilirubin 190.0 μmol/l). The child had a special phenotype: asymmetry of the body with a relative increase in head circumference, a small triangular face with a protruding forehead, a narrow chin, a small jaw, and curvature of the 5th finger. From birth, insufficient body weight gain was observed (60 g per week, 400 g from birth in 6 weeks), which was explained by physiological vomiting and lactase deficiency (homozygous carrier of genotype C/C during PCR analysis). Body weight at the age of 1 year 5.200 g, height 63 cm, at the age of 5 years body weight 10.2 kg, height 91 cm. The child had heightened intellectual and psychological development. For the sake of differential diagnosis, a study was conducted for the presence of Gaucher’s disease (the result was negative). The results of immunologic tests: IgA 0.77 g/l, tTgIgA&lt; 2.0 units/ml, and tTgIgG 0.05 denied the presence of celiac disease. Clinical diagnosis was established according to the Netchine-Harbison scoring system (NH-CSS), which consists of 6 clinical criteria of NH-CSS. Gene sequencing revealed changes in the variant of uncertain significance SLK25A15, the genetic significance of which is unknown, which did not allow to confirm the diagnosis. Invitae Chromoso-mal Microarray Analysis of genome research on microdeletions (duplications) revealed, with a normal female genomic profile, uniparental dysfunction with two areas of homozygosity ROH&gt;5Mb (GRCh370) in chromosome 20: 20q13-p12.3(1-6690101; 6.69Mb and 20q13.32- q13.33(57394420- 63025520); 5.63 Mb. This change is characterized as a SRS variant, which created the basis for the diagnosis. Therefore, the child has a genetically confirmed diagnosis of SRS and congenital lactose intolerance. Somatotropic hormone (Omnitrop) was prescribed at a dose of 0.6 mg/day continuously. Conclusions: 1. The child’s SRS diagnosis was established on the basis of phenotype data, slow weight gain and growth, genetic research data, and the exclusion of the possibility of other conditions with the impaired physical development of the child. 2. The child needs a multidisciplinary approach to observation and treatment by a pediatrician or family doctor, endocrinologist, geneticist, nutritionist, surgeon, and gynecologist.

Testicular damage without clinical manifestations in BALB/c mice experimentally infected with Zika virus.

In 2015-2016, the Zika virus (ZIKV) caused a major epidemic in the Americas, increasing cases of microcephaly and Guillain-Barré syndrome. During this period, the discovery of ZIKV sexual transmission intensified studies on the impact of this virus on the reproductive organs. For this study, 2-month-old male BALB/c mice were infected with 1.26 x 106 PFU/mL of ZIKV in solution via the intravenous route. After three, seven, and fourteen days post-infection (DPI), blood and testicle samples were obtained to detect ZIKV RNA. The authors observed that the infected animals had slower weight gain than the control group. Viremia occurred only at 3DPI, and the ZIKV RNA was detected in one testis sample at 7DPI. The histopathological analysis of this organ revealed intense disorganization of the seminiferous tubules' structure, inflammatory infiltrate, necrosis, hemorrhage, fluid accumulation, congestion of blood vessels, and reduced sperm count. Ultrastructural analysis showed nuclear changes in tubule cells, activation of interstitial cells, and morphological changes in spermatozoa, in addition to fragmentation and decreased electron density of the genetic material of these cells. Thus, despite causing predominantly asymptomatic infections, ZIKV can cause significant subclinical and transient damage, including to male reproductive organs.

The ameliorative mechanism of Lactiplantibacillus plantarum NJAU-01 against D-galactose induced oxidative stress: a hepatic proteomics and gut microbiota analysis.

Probiotic intervention is an effective strategy to alleviate oxidative stress-related diseases. Our previous studies found that Lactiplantibacillus plantarum NJAU-01 (NJAU-01) exhibited antioxidant effects in a D-galactose (D-gal)-induced aging mouse model. However, the underlying mechanism remains to be unveiled. This study was aimed to investigate the ameliorative effect and mechanism of NJAU-01 against oxidative stress induced by D-gal. The results showed that NJAU-01 could reverse the tendency of a slow body weight gain induced by D-gal. NJAU-01 relieved hepatic oxidative stress via increasing the hepatic total antioxidant capacity and antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Moreover, the malondialdehyde (MDA) level was reversed after NJAU-01 supplementation. The proteomic results showed that there were 201 differentially expressed proteins (DEPs) between NJAU-01 and D-gal groups. NJAU-01 regulated the expressions of glutathione S-transferase Mu 5 (Gstm5), glutathione S-transferase P2 (Gstp2) and NADH dehydrogenase 1α subcomplex subunit 7 (Ndufa7) related to oxidative stress, and autophagy protein 5 (Atg5) and plasma alpha-L-fucosidase (Fuca2) involved in autophagy, etc. 16S rDNA sequencing results showed that NJAU-01 supplementation could regulate the gut microbiota dysbiosis induced by D-gal via increasing the relative abundances of the phylum Firmicutes and the genus Lactobacillus and reducing the relative abundances of the phylum Bacteroidetes and the genera Lachnospiraceae_NK4A136_group as well as Prevotellaceae_UCG-001, etc.. Spearman correlation analysis results showed that the altered gut microbiota composition had a significant correlation with antioxidant enzyme activities and the DEPs related to oxidative stress. Overall, NJAU-01 alleviated hepatic oxidative stress induced by D-gal via manipulating the gut microbiota composition and hepatic protein expression profile.

Preterm Formula, Fortified or Unfortified Human Milk for Very Preterm Infants, the PREMFOOD Study: A Parallel Randomised Feasibility Trial

Objective: Uncertainty exists regarding optimal supplemental diet for very preterm infants if the mother’s own milk (MM) is insufficient. We evaluated feasibility for a randomised controlled trial (RCT) powered to detect important differences in health outcomes. Methods: In this open, parallel, feasibility trial, we randomised infants 25+0–31+6 weeks of gestation by opt-out consent to one of three diets: unfortified human milk (UHM) (unfortified MM and/or unfortified pasteurised human donor milk (DM) supplement), fortified human milk (FHM) (fortified MM and/or fortified DM supplement), and unfortified MM and/or preterm formula (PTF) supplement from birth to 35+0 weeks post menstrual age. Feasibility outcomes included opt-outs, adherence rates, and slow growth safety criteria. We also obtained anthropometry, and magnetic resonance imaging body composition data at term and term plus 6 weeks (opt-in consent). Results: Of 35 infants randomised to UHM, 34 to FHM, and 34 to PTF groups, 21, 19, and 24 infants completed imaging at term, respectively. Study entry opt-out rate was 38%; 6% of parents subsequently withdrew from feeding intervention. Two infants met predefined slow weight gain thresholds. There were no significant between-group differences in term total adipose tissue volume (mean [SD]: UHM: 0.870 L [0.35 L]; FHM: 0.889 L [0.31 L]; PTF: 0.809 L [0.25 L], p = 0.66), nor in any other body composition measure or anthropometry at either timepoint. Conclusions: Randomisation to UHM, FHM, and PTF diets by opt-out consent was acceptable to parents and clinical teams, associated with safe growth profiles and no significant differences in body composition. Our data provide justification to proceed to a larger RCT.