Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases

Neurodegenerative disorders affect more than fifty million Americans each year and represent serious health threats as the population ages. Neuroinflammation and oxidative stress are critical in the onset, progression, and pathogenesis of neurodegenerative diseases such as Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS). A wide range of natural compounds has been investigated because of their antioxidant, anti-inflammatory, and neuroprotective properties. The citrus flavonoid hesperetin (HPT), an aglycone of hesperidin found in oranges, mandarins, and lemons, has been extensively reported to exert neuroprotective effects in experimental models of neurogenerative diseases. This review has compiled multiple studies on HPT in both in vivo and in vitro models to study neurodegeneration. We focused on the modulatory effects of hesperetin on the release of cellular anti-inflammatory and antioxidative stress mediators. Additionally, this review discusses the hesperetin effect in maintaining the levels of microRNA (miRNA) and modulating autophagy as it relates to hesperetin’s protective mechanisms against neurodegeneration. Moreover, this review is focused on providing experimental data for hesperetin’s potential as a neuroprotective compound and discusses reported evidence that HPT crosses the blood–brain barrier. In summary, this review shows the evidence available in the literature to indicate the efficacy of hesperetin in delaying the onset of neurodegenerative diseases.     

Effects of Phosphoethanolamine Supplementation on Mitochondrial Activity and Lipogenesis in a Caffeine Ingestion Caenorhabditis elegans Model

Caffeine intake is strongly linked to lipid metabolism. We previously reported the age-dependent physiological effects of caffeine intake in a Caenorhabditis elegans model. Since nutritional status can actively influence metabolism and overall health, in this study, we evaluated the effect of caffeine intake on lipid metabolism in adult-stage C. elegans. We found that, in C. elegans, fat storage and the level of phosphoethanolamine (PE) were significantly reduced with caffeine intake. In addition, mitochondrial activity decreased and mitochondrial morphology was disrupted, and the expression of oxidative stress response genes, hsp-6, gst-4, and daf-16, was induced by caffeine intake. Furthermore, the level of an energy metabolism sensor, phospho-AMP-activated protein kinase, was increased, whereas the expression of the sterol regulatory element binding protein gene and its target stearoyl-CoA desaturase genes, fat-5, -6, and -7, was decreased with caffeine intake. These findings suggest that caffeine intake causes mitochondrial dysfunction and reduces lipogenesis. Interestingly, these changes induced by caffeine intake were partially alleviated by PE supplementation, suggesting that the reduction in mitochondrial activity and lipogenesis is in part because of the low PE level, and proper dietary supplementation can improve organelle integrity.     

Beneficial Effects of Partly Milled Highland Barley on the Prevention of High-Fat Diet-Induced Glycometabolic Disorder and the Modulation of Gut Microbiota in Mice

The nutritional functions of highland barley (HB) are superior to those of regular cereals and have attracted increasing attention in recent years. The objective of this study was to investigate whether partly milled highland barley (PHB) can regulate the serum glucose and lipid disorders of mice fed a high-fat diet (HFD) and to further explore their potential gut microbiota modulatory effect. Our results showed that PHB supplementation significantly reduced fasting blood glucose (FBG) and improved oral glucose tolerance. Histological observations confirmed the ability of PHB to alleviate liver and intestine damage. Furthermore, the results of 16S amplicon sequencing revealed that PHB prevented a HFD-induced gut microbiota dysbiosis, enriching some beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Ileibacterium, and reducing several HFD-dependent taxa (norank_f_Desulfovibrionaceae, Blautia, norank_f_Lachnospiraceae, unclassified_f_Lachnospiraceae, and Colidextribacter). In addition, the increase of Lactobacillus and Bifidobacterium presence has a slightly dose-dependent relationship with the amount of the added PHB. Spearman correlation analysis revealed that Lactobacillus and Bifidobacterium were negatively correlated with the blood glucose level of the oral glucose tolerance test. Overall, our results provide important information about the processing of highland barley to retain its hypoglycemic effect and improve its acceptability and biosafety.     

Effects of Soy Isoflavones,Resistant Starch and Antibiotics on Polycystic Ovary Syndrome (PCOS)-Like Features in Letrozole-Treated Rats

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Recently, various dietary interventions have been used extensively as a novel therapy against PCOS. In the present study, we show that soy isoflavone metabolites and resistant starch, together with gut microbiota modulations, were successful in decreasing the severity of PCOS-like reproductive features while increasing the expression of gut barrier markers and butyric acid in the gut. In the letrozole-induced PCOS model rats, the intake of both 0.05% soy isoflavones and 11% resistant starch, even with letrozole treatment, reduced the severity of menstrual irregularity and polycystic ovaries with a high concentration of soy isoflavones and equol in plasma. Antibiotic cocktail treatment suppressed soy isoflavone metabolism in the gut and showed no considerable effects on reducing the PCOS-like symptoms. The mRNA expression level of occludin significantly increased with soy isoflavone and resistant starch combined treatment. Bacterial genera such as Blautia, Dorea and Clostridium were positively correlated with menstrual irregularity under resistant starch intake. Moreover, the concentration of butyric acid was elevated by resistant starch intake. In conclusion, we propose that both dietary interventions and gut microbiota modulations could be effectively used in reducing the severity of PCOS reproductive features.     

A Biomonitoring Study Assessing the Residual Biological Effects of Pollution Caused by the HAVEN Wreck on Marine Organisms in the Ligurian Sea (Italy)

Residual biological effects of the 1991 HAVEN oil spill off the Ligurian (Arenzano) coast were assessed in this study. Samples of the fish species Boops boops, Mullus barbatus, and Uranoscupus scaber were collected from two polluted sites near the HAVEN wreck and from an uncontaminated area. In addition to this, mussels were caged along the coast affected by the HAVEN disaster. The physiological status of fish and mussels was assessed using a battery of stress and exposure biomarkers. The PAH content of mussel and fish tissues was also analyzed. Significant biological responses were observed in lysosomal membrane stability, neutral lipid and lipofuscin accumulation and micronucleus frequency for mussels caged at two sites close to the HAVEN wreck. Chemical analyses indicated, however, that these effects are not caused by aromatic hydrocarbons. For this reason, we suggest that the aftermath of the HAVEN disaster contributes very little to coastal ecosystem pollution. This was also confirmed by the few biological effects observed in fish specimens (Boops boops) collected from surface waters. Nevertheless, it is important to point out that benthic fish displayed a stress syndrome potentially caused by aromatic hydrocarbons released from the oil tanker, as witnessed by an enhanced EROD activity and increased lipofuscin and neutral lipid lysosomal contents.     

A Review of the Effects of Bromate on Aquatic Organisms and Toxicity of Bromate to Oyster (Crassostrea gigas) Embryos

A critical literature review has been undertaken of the effects that bromate (BrO⁻₃) has on aquatic organisms. Chronic (multigeneration) studies using four marine phytoplankton species indicate a stimulation of cell division at concentrations up to 13.6 mg BrO⁻₃liter⁻¹, such that the EC₅₀is >13.6 mg BrO⁻₃liter⁻¹(exposure period unspecified). No published data were available for any freshwater algal or phytoplankton species. For freshwater invertebrates, the available data are limited to acute studies using two species: the water flea,Daphnia magna,with a 48-h LC₅₀of 179 mg BrO⁻₃liter⁻¹; and the planarian (“flatworm”),Polycelis nigra,with a 48-h LC₅₀of 2258 mg BrO⁻₃liter⁻¹. For saltwater invertebrates, there is a greater variety in the spread of species sensitivity to bromate. For crustaceans, the lowest reported acute value is a 24-h LC₅₀of 176 mg BrO⁻₃liter⁻¹for mysid shrimp. For molluscs, the published data are somewhat contradictory, with different workers reporting EC₅₀values to oyster embryo–larvae of either 0.05–0.1 or 30 mg BrO⁻₃liter⁻¹. Following repeated attempts to resolve these differences using the Pacific oyster (Crassostrea gigas) embryo development assay, a 24-h EC₅₀of 170 mg BrO⁻₃liter⁻¹was observed. Reported 96-h LC₅₀values for juvenile saltwater fish range from 427 to 512 mg BrO⁻₃liter⁻¹, while a 10-day LC₅₀of 279 mg BrO⁻₃liter⁻¹is also reported. For fish early lifestages, newly hatched larvae are more sensitive than embryo hatching, with a larval 96-h LC₅₀of 31 mg BrO⁻₃liter⁻¹being observed. Less severe effects have been reported for older larvae (pro-larvae), for which a 96-h LC₅₀of 404 mg BrO⁻₃liter⁻¹is reported. In conclusion, a number of studies provide evidence for the acute toxicity of bromate to invertebrates and fish in the lowest region of 30 mg BrO⁻₃liter⁻¹. Applying the factor of 10 used to extrapolate from acute to potential chronic toxicity, the available data suggest that to protect aquatic organisms from long-term adverse effects, concentrations should not exceed approximately 3.0 mg BrO⁻₃liter⁻¹.     

Beneficial Effects of Walnut Oligopeptides on Muscle Loss in Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice: Focusing on Mitochondrial Function

Aging-related muscle loss is a hallmark of aging and is the cause of some negative outcomes. An optimized diet and supplements have a positive effect in slowing down the process of muscle loss. This study was designed to evaluate the beneficial effects of walnut oligopeptides (WOPs) on aging-related muscle loss and explore the possible underlying mechanism in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice. SAMP8 mice were randomly divided into four groups (n = 15/group), including one group which was the SAMP8 age control group and three groups those were WOP intervention groups. Meanwhile, Senescence Accelerated Resistant Mouse 1 (SAMR1) mice (n = 12), which had normal senescence rates, were used as model controls. During the six-month intervention period, the age control and normal control groups were given sterilized water, while the three WOP intervention groups were given WOP solution with low (110 mg/kg·bw), medium (220 mg/kg·bw) and high concentrations (440 mg/kg·bw), respectively. The results showed that WOPs could significantly increase muscle mass and improve physical performance (wire hang and catwalk behavioral tests) in aging mice. Moreover, WOPs could significantly reduce the levels of IL-1β, IL-6 and TNF-α in serum and gastrocnemius tissues and increase the mitochondrial DNA content, as well as the expression levels of AMPK, PGC-1α, NRF-1 and TFAM in the gastrocnemius muscle of aging mice, which was speculated to be the specific mechanism related to mitochondrial function improvement and inflammation reduction. These results indicate that WOPs can improve aging-related muscle loss, in term of both muscle mass and physical performance, and WOP supplements seems to be potentially effective in elderly individuals.     

Time- and Dose-Related Effects of Di-(2-ethylhexyl) Phthalate and Its Main Metabolites on the Function of the Rat Fetal Testis in Vitro

Background

Endocrine-disrupting effects of phthalates are understood primarily from in utero exposures within the fetal rat testis. Nevertheless, their path of action, dose–response character, and cellular target(s) within the fetal testis are not known.

Objectives

In this study we investigated the effects of di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP), and several of their metabolites on the development of organo-cultured testes from rat fetus.

Methods

We removed testes from 14.5-day-old rat fetuses and cultured them for 1–3 days with or without DEHP, MEHP, and the metabolites.

Results

DEHP (10⁻⁵ M) produced a proandrogenic effect after 3 days of culture, whereas MEHP disrupted testis morphology and function. Leydig cells were the first affected by MEHP, with a number of them being inappropriately located within some seminiferous tubules. Additionally, we found a time- and dose-dependent reduction of testosterone. By 48 hr, gonocyte proliferation had decreased, whereas apoptosis increased. Sertoli cell number was unaffected, although some cells appeared vacuolated, and production of anti-Müllerian hormone decreased in a time- and dose-dependent manner. The derived metabolite mono-(2-ethyl-5-hydroxyhexyl) phthalate was the only one to cause deleterious effects to the rat fetal testis in vitro.

Conclusion

We hope that this in vitro method will facilitate the study of different phthalate esters and other endocrine disruptors for direct testicular effects.     

Variability over 1 Week in the Urinary Concentrations of Metabolites of Diethyl Phthalate and Di(2-Ethylhexyl) Phthalate among Eight Adults: An Observational Study

Background

Phthalates are metabolized and eliminated in urine within hours after exposure. Several reports suggest that concentrations of phthalate metabolites in a spot urine sample can provide a reliable estimation of exposure to phthalates for up to several months.

Objectives

We examined inter- and intraperson and inter- and intraday variability in the concentrations of monoethyl phthalate (MEP), the major metabolite of diethyl phthalate, commonly used in personal care products, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), a polyvinyl chloride plasticizer of which diet is the principal exposure source, among eight adults who collected all urine voids (average, 7.6 samples/person/day) for 1 week.

Methods

We analyzed the urine samples using online solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry.

Results

Regardless of the type of void (spot, first morning, 24-hr collection), for MEP, interperson variability in concentrations accounted for > 75% of the total variance. By contrast, for MEHHP, within-person variability was the main contributor (69–83%) of the total variance. Furthermore, we observed considerable intraday variability in the concentrations of spot samples for MEHHP (51%) and MEP (21%).

Conclusions

MEP and MEHHP urinary concentrations varied considerably during 1 week, but the main contributors to the total variance differed (interday variability, MEHHP; interperson variability, MEP) regardless of the sampling strategy (spot, first morning, 24-hr collection). The nature of the exposure (diet vs. other lifestyle factors) and timing of urine sampling to evaluate exposure to phthalates should be considered. For DEHP and phthalates to which people are mostly exposed through diet, collecting 24-hr voids for only 1 day may not be advantageous compared with multiple spot collections. When collecting multiple spot urine samples, changing the time of collection may provide the most complete approach to assess exposure to diverse phthalates.     

Effects of Fermented Milk Containing Bifidobacterium animalis Subsp. lactis MN-Gup (MN-Gup) and MN-Gup-Based Synbiotics on Obesity Induced by High Fat Diet in Rats

Given the probiotic effects previously found in Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and its great application potential in dairy products, this study aimed to investigate the effects of fermented milk containing MN-Gup or MN-Gup-based synbiotics on high fat diet (HFD)-induced obesity in rats. Galacto-oligosaccharides (GOS) and xylo-oligosaccharides (XOS) were selected as the tested prebiotics in MN-Gup-based synbiotics due to their promotion of MN-Gup growth in vitro. After nine weeks of HFD feeding, the obese rats were intervened with fermented milk containing MN-Gup (MN-Gup FM) or its synbiotics (MN-Gup + GOS FM, MN-Gup + XOS FM) for eight weeks. The results showed that the interventions could alleviate HFD-induced body weight gain, epididymal fat deposition, adipocyte hypertrophy, dyslipidemia and inflammation, but GOS and XOS did not exhibit significant synergies with MN-Gup on those alleviations. Furthermore, the interventions could regulate the HFD-affected gut microbiota and microbial metabolites, as shown by the increases in short chain fatty acids (SCFAs) and alterations in obesity-related bile acids (BAs), which may play important roles in the mechanism underlying the alleviation of obesity. This study revealed the probiotic effects of MN-Gup on alleviating obesity and provided the basis for MN-Gup applications in the future.     

Effects of bitter melon (Momordica charantia L.) on the gut microbiota in high fat diet and low dose streptozocin-induced rats

The effects on gut microbiota of type 2 diabetic rats fed a bitter melon formulation (BLSP, a lyophilized superfine powder) were investigated. BLSP treatment significantly reduced fasting blood glucose levels (p?p?Firmicutes to Bacteroidetes in diabetic rats, while the relative abundances of Ruminococcaceae, Bacteroides and Ruminococcus were significantly lowered in BLSP-treated rats compared to diabetic rats. Additionally, BLSP significantly suppressed the activation of MAPK (JNK and p38). The results indicate that BLSP can significantly modify the proportions of particular gut microbiota in diabetic rats without disturbing the normal population diversity. By suppressing the activation of MAPK signaling pathway, a BLSP containing diet may ameliorate type 2 diabetes.     

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin^® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin^® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin^® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin^® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin^® effects. Accordingly, AphaMax^®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin^® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin^® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin^® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.     

Updated Information of the Effects of (Poly)phenols against Type-2 Diabetes Mellitus in Humans: Reinforcing the Recommendations for Future Research

(Poly)phenols have anti-diabetic properties that are mediated through the regulation of the main biomarkers associated with type 2 diabetes mellitus (T2DM) (fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (IR)), as well as the modulation of other metabolic, inflammatory and oxidative stress pathways. A wide range of human and pre-clinical studies supports these effects for different plant products containing mixed (poly)phenols (e.g., berries, cocoa, tea) and for some single compounds (e.g., resveratrol). We went through some of the latest human intervention trials and pre-clinical studies looking at (poly)phenols against T2DM to update the current evidence and to examine the progress in this field to achieve consistent proof of the anti-diabetic benefits of these compounds. Overall, the reported effects remain small and highly variable, and the accumulated data are still limited and contradictory, as shown by recent meta-analyses. We found newly published studies with better experimental strategies, but there were also examples of studies that still need to be improved. Herein, we highlight some of the main aspects that still need to be considered in future studies and reinforce the messages that need to be taken on board to achieve consistent evidence of the anti-diabetic effects of (poly)phenols.     

Effect and Tolerability of a Nutritional Supplement Based on a Synergistic Combination of β-Glucans and Selenium- and Zinc-Enriched Saccharomyces cerevisiae (ABB C1®) in Volunteers Receiving the Influenza or the COVID-19 Vaccine: A Randomized,Double-Blind,Placebo-Controlled Study

A single-center, randomized, double-blind, placebo-controlled study was conducted in 72 volunteers who received a synergistic combination of yeast-based ingredients with a unique β-1,3/1,6-glucan complex and a consortium of heat-treated probiotic Saccharomyces cerevisiae rich in selenium and zinc (ABB C1^®) or placebo on the next day after getting vaccinated against influenza (Chiromas^®) (n = 34) or the COVID-19 (Comirnaty^®) (n = 38). The duration of treatment was 30 and 35 days for the influenza and COVID-19 vaccine groups, respectively. Mean levels of CD4+T cells increased from 910.7 at baseline to 1000.2 cells/µL after the second dose of the COVID-19 vaccine in the ABB C1^® group, whereas there was a decrease from 1055.1 to 929.8 cells/µL in the placebo group. Changes of CD3+T and CD8+T lymphocytes showed a similar trend. In the COVID-19 cohort, the increases in both IgG and IgM were higher in the ABB C1^® supplement than in the placebo group. Serum levels of selenium and zinc showed a higher increase in subjects treated with the active product than in those receiving placebo. No serious adverse events related to ABB C1^® or tolerance issues were reported. The study findings validate the capacity of the ABB C1^® product to stimulate trained immunity.     

温石棉对人支气管上皮细胞BEAS-2B凋亡的影响

[目的]研究温石棉对永生化人支气管上皮细胞（BEAS-2B）凋亡的影响,比较单细胞凝胶电泳试验（SCGE）与流式细胞术（FCM）检测细胞凋亡结果的异同。[方法]选用BEAS-2B细胞为受试物,以5、10,20、40、100、200μg／cm^2不同剂量的温石棉,分别刺激BEAS-2B细胞24、48、72h,阳性对照用石英（SiO2）,阴性对照用硅灰石（WO1）,用四甲基偶氮唑盐（MTT）比色法检测温石棉对BEAS-2B活力的影响。用终剂量10μg／cm^2温石棉、5μg／cm^2 SiO2、20μg／cm^2 WO1分别刺激细胞24、48和72h后,采用SCGE和FCM检测温石棉对BEAS-2B凋亡指数和凋亡率的影响。采用逆转录聚合酶链反应（RT-PCR）技术检测凋亡相关半胱氨酸蛋白酶-3基因caspase-3、caspase-9的表达。[结果]10μg／cm^2温石棉可诱导BEAS-2B细胞凋亡,呈时间-效应关系（P〈0.05）,采用SCGE和FCM方法检测细胞凋亡率结果一致。温石棉刺激BEAS.2B细胞24、48、72h后凋亡指数为11.7％、21.8％和34.5％,凋亡率为9.6％、17.9％和31.2％;温石棉诱导细胞caspase-3、caspase-9表达水平随时间增加而增加。[结论]温石棉可诱导BEAS-2B凋亡;SCGE和FCM均可以灵敏、快捷地检测温石棉对BEAS-2B的凋亡作用。     

Impact of Seasonal Consumption of Local Tomatoes on the Metabolism and Absorption of (Poly)Phenols in Fischer Rats

Consuming (poly)phenol-rich fruits and vegetables, including tomato, is associated with health benefits. The health effects of tomato (poly)phenolic compounds have been attributed to their metabolites rather than parent compounds and their bioavailability can be modulated by several factors. This study aimed to evaluate the effect of seasonal consumption of local tomatoes on their (poly)phenol bioavailability. For this, (poly)phenol absorption and metabolism were evaluated by ultra-high-performance liquid chromatography coupled with mass spectrometry and linear ion trap mass spectrometric (uHPLC-MSⁿ) after chronic tomato consumption in Fischer rats exposed to three photoperiods mimicking the seasonal daylight schedule. Tomatoes from two locations in Spain (LT, local tomatoes and NLT, non-local tomatoes) were used in this in vivo feeding study. The bioavailability of tomato (poly)phenols depended on the photoperiod to which the rats were exposed, the metabolite concentrations significantly varying between seasons. In-season tomato consumption allowed obtaining the highest concentration of total circulating metabolites. In addition, the origin of the tomato administered generated marked differences in the metabolic profiles, with higher serum concentrations reached upon NLT ingestion. We concluded that in-season tomato consumption led to an increase in (poly)phenol circulation, whereas LT consumption showed lower circulating metabolites than NLT ones. Thus, the origin of the tomato and the seasonal daylight schedule affect the bioavailability of tomato (poly)phenols, which could also affect their bioactivity.     

Effects of methyltestosterone on reproduction in the Japanese quail (Coturnix coturnix japonica)

Although the hormone-mediated effects of the synthetic androgenic hormone methyltestosterone (MT) are well characterized in mammals, little is known about endocrine and other toxic effects on reproduction in birds. In a one-generation study, MT was administered to adult Japanese quail (12 pairs per group) at dietary dose levels of 0, 10, 50, and 110 ppm for a period of 3 weeks. Reproductive performance was severely affected in the groups receiving 50 and 110 ppm MT. In females, the egg-laying rate was reduced not only related to the dose administered but also to the duration of treatment. The administration of 110 ppm, and to a lesser extent, of 50 ppm MT resulted in an immediate and dramatic decrease in the total number of eggs laid, which complicated reliable assessment of other reproduction-related parameters. In males, the findings suggested inhibition of spermatogenesis at dose levels of 50 ppm and above, resulting in a subsequent reduction in male fertility.     

Recommendations on Complementary Feeding as a Tool for Prevention of Non-Communicable Diseases (NCDs)—Paper Co-Drafted by the SIPPS,FIMP, SIDOHaD,and SINUPE Joint Working Group

Adequate and balanced nutrition is essential to promote optimal child growth and a long and healthy life. After breastfeeding, the second step is the introduction of complementary feeding (CF), a process that typically covers the period from 6 to 24 months of age. This process is, however, still highly controversial, as it is heavily influenced by socio-cultural choices, as well as by the availability of specific local foods, by family traditions, and pediatrician beliefs. The Società Italiana di Pediatria Preventiva e Sociale (SIPPS) together with the Federazione Italiana Medici Pediatri (FIMP), the Società Italiana per lo Sviluppo e le Origine della Salute e delle Malattie (SIDOHaD), and the Società Italiana di Nutrizione Pediatrica (SINUPE) have developed evidence-based recommendations for CF, given the importance of nutrition in the first 1000 days of life in influencing even long-term health outcomes. This paper includes 38 recommendations, all of them strictly evidence-based and overall addressed to developed countries. The recommendations in question cover several topics such as the appropriate age for the introduction of CF, the most appropriate quantitative and qualitative modalities to be chosen, and the relationship between CF and the development of Non-Communicable Diseases (NCDs) later in life.