Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice.

BACKGROUND: The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of parents of reproductive age consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father's poor nutritional status has been shown to have negative consequences on foetal growth and development and ultimately impact the long-term adult health of the offspring. In this study, we examined sperm- and seminal vesicle fluid-mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. RESULTS: Male mice were fed a diet to model either under (low-protein diet (LPD)) or over (high-fat/sugar 'Western' diet (WD)) nutrition, LPD or WD supplemented with methyl donors or a control diet (CD) before mating with age-matched females. Male metabolic health was influenced by WD and MD-WD, with significant changes in multiple serum lipid classes and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35 transcripts). Separate analysis of the seminal vesicle fluid proteome revealed a significant number of differentially expressed proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. Following mating, in vitro time-lapse imaging of preimplantation embryos revealed a significant increase in the timing of development in all experimental groups when compared to CD embryos. Finally, qPCR analysis of uterine tissue at the time of implantation identified perturbed expression of Cd14 and Ptgs1 following mating with WD-fed males. CONCLUSIONS: Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive health, impacting on embryonic development and the maternal reproductive tract. This study highlights potential direct (sperm-mediated) and indirect (seminal vesicle fluid-mediated) pathways in which a father's poor diet could shape the long-term health of his offspring.

Bridging the gap: Prenatal nutrition, myelination, and schizophrenia etiopathogenesis.

Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management.

Relationship between oral status, swallowing function, and nutritional risk in older people with and without Parkinson's disease. / Relação entre estado oral, função de deglutição e risco nutricional entre idosos com e sem doença de Parkinson.

PURPOSE: To compare oral status, swallowing function (through instrumental and SLH assessment), and nutritional risk between dysphagic individuals with and without Parkinson's disease. METHOD: This is a cross-sectional retrospective study based on data collected from medical records. It included 54 dysphagic older adults, divided into two groups according to the diagnosis of Parkinson's disease. The study collected data on the speech-language-hearing assessment of postural control, tongue mobility and strength, maximum phonation time (MPT), and cough efficiency. Oral status was assessed using the number of teeth and the Eichner Index. The level of oral intake and pharyngeal signs of dysphagia were analyzed with four food consistencies, according to the International Dysphagia Diet Standardization Initiative classification, using fiberoptic endoscopic evaluation of swallowing, for comparison between groups. The severity of pharyngeal residues was analyzed and classified with the Yale Pharyngeal Residue Severity Rating Scale, and the nutritional risk was screened with the Malnutrition Screening Tool. RESULTS: The group of older adults with Parkinson's disease was significantly different from the other group in that they had fewer teeth, unstable postural control, reduced tongue strength, reduced MPT, weak spontaneous coughing, pharyngeal signs, less oral intake, and nutritional risk. CONCLUSION: Dysphagic older people with Parkinson's disease had different oral status, swallowing function, and nutritional risk from those without the diagnosis.

OBJETIVO: Comparar o estado oral, a função de deglutição por meio da avaliação instrumental, fonoaudiológica e do risco nutricional entre indivíduos disfágicos com e sem doença de Parkinson. MÉTODO: Trata-se de um estudo transversal e retrospectivo com base na coleta de dados dos prontuários. Foram incluídos 54 idosos disfágicos divididos em dois grupos, de acordo com a presença do diagnóstico de doença de Parkinson. Foram coletados dados com relação à avaliação fonoaudiológica de controle postural, mobilidade e força de língua, Tempo Máximo de Fonação (TMF) e eficiência da tosse. O estado oral foi avaliado por meio do número de dentes e o Índice de Eichner. Foram analisados o nível de ingestão oral e os sinais faríngeos de disfagia em quatro consistências alimentares, de acordo com a classificação International Dysphagia Diet Standardisation Initiative (IDDSI), por meio da videoendoscopia da deglutição, para comparação entre os grupos. Para análise e classificação da gravidade dos resíduos faríngeos, foi utilizado o Yale Pharyngeal Residue Severity Rating Scale (YPRSRS), enquanto que, para rastrear o risco nutricional foi utilizado o Malnutrition Screening Tool (MST). RESULTADOS: O grupo de idosos com doença de Parkinson apresentou diferença significativa em menor número de dentes, controle postural instável, força de língua reduzida, TMF reduzido, tosse espontânea fraca, sinais faríngeos, nível de ingestão oral menor e em risco nutricional, em comparação ao outro grupo. CONCLUSÃO: Os idosos disfágicos com doença de Parkinson apresentaram diferenças no estado oral, na função de deglutição e no risco nutricional em comparação àqueles sem o diagnóstico.

Predictive value of the controlling nutritional status (CONUT) score to assess long-term mortality (10 Years) in patients with hypertension.

BACKGROUND AND AIMS: Malnutrition is associated with poor outcomes in patients with chronic diseases. The aim of this study is to investigate the prevalence of malnutrition in patients with hypertension and relationship between malnutrition severity and long-term mortality in these patients. METHODS AND RESULTS: The study included 11,278 patients with hypertension from the National Health and Nutrition Examination Survey database. The degree of malnutrition was assessed using the Controlled Nutritional Status score, with patients divided into normal, mild, and moderate-to-severe groups. After 10 years of follow-up, the results showed that patients who died had higher CONUT scores, poorer nutritional status, and lower albumin, total cholesterol, and lymphocytes than those who survived (P < 0.05). The Kaplan-Meier analysis revealed that patients with poor nutritional status had a significantly higher risk of all-cause death. In the Non-Lipid Lowering Drugs group, the CONUT score (hazard ratio (HR): 1.225; 95% confidence interval (CI): 1.162-1.292; P < 0.0001), as well as mild (HR: 1.532; 95% CI 1.340-1.751; P < 0.0001) and moderate-to-severe malnutrition (HR: 2.797; 95% CI: 1.441-5.428; P = 0.0024), were independent predictors of long-term mortality. The competing risk regression models showed that cardiovascular and cerebrovascular mortality increased with increasing CONUT scores. The results were robust in both subgroup and sensitivity analyses. CONCLUSIONS: Malnutrition significantly impacts long-term mortality in hypertensive patients. The CONUT score may be a useful tool for assessing the nutritional status of patients with hypertension in the non-lipid-lowering population and for predicting their long-term mortality.

[Relationship between cognitive status and other geriatric syndromes in patients aged 65 years and older with chronic heart failure.]

This article presents the incidence of geriatric syndromes in patients with chronic heart failure 65 years of age and older, depending on cognitive status. At the Russian gerontological center, 149 people with confirmed chronic heart failure were selected according to the European criteria of 2021. In this sample, 50,3% of patients had mild cognitive impairment, and 17,5% had severe cognitive impairment. With age, the incidence and severity of cognitive impairment increased. Among patients with cognitive impairment, there were more patients with reduced basic and instrumental activities of daily living, with a high risk of malnutrition and malnutrition, frailty and patients with hearing loss. Also, as cognitive functions declined, the median score of the Barthel and Lawton index, the mini nutritional assessment, the short physical performance battery, the Lubben social network scale decreased, and the median of the Morse fall risk scale and the geriatric depression scale increased. The presence of hearing loss was associated with a 3,6-fold increase in the odds of being diagnosed with cognitive impairment, and the presence of frailty syndrome, basic dependence in daily life, or the risk of malnutrition by a 2,4-fold increase.

Interrelationship between Altered Left Ventricular Ejection Fraction and Nutritional Status in the Post-Acute Myocardial Infarction Patient.

There is currently little research on the effects of reduced left ventricular ejection fraction and altered nutritional status in patients with acute myocardial infarction. We therefore examined the interrelationship between the parameters of left ventricular dysfunction after acute myocardial infarction and changes in the Geriatric Nutrition Risk Index (GNRI) and the Nutrition Status Control Index (CONUT). Based on the evidence, frailty is considered to be an important factor affecting the prognosis of cardiovascular disease, so it is important to detect malnutrition early to prevent adverse cardiovascular events. This study was an observational, prospective study that included a total of 73 subjects who presented at the 3-month AMI follow-up. All subjects were subjected to laboratory tests and the groups were divided as follows: group 1, in which we calculated the CONUT score, (CONUT < 3 points, n = 57) patients with normal nutritional status and patients with moderate to severe nutritional deficiency (CONUT ≥ 3, n = 16). In group 2, the GNRI score was calculated and out of the 73 patients we had: GNRI ≥ 98, n = 50, patients with normal nutritional status, and GNRI < 98, n = 23, patients with altered nutritional status. The results of this study showed that we had significant differences between LVEF values at 3 months post-infarction where, in the CONUT group, patients with altered nutritional status had lower LVEF values (46.63 ± 3.27% versus 42.94 ± 2.54%, p < 0.001) compared to CONUT < 3. Also, in the GNRI group, we had lower LVEF values in patients with impaired nutritional status (46.48 ± 3.35% versus 44.39 ± 3.35%, p = 0.01). It can be seen that LVEF values are improved at 3 months post infarction in both groups, in patients with impaired nutritional status and in patients with good nutritional status. Patients with impaired nutritional status have lower ejection fraction and worse outcomes in both the CONUT and GNRI groups at 3 months post acute myocardial infarction.

Effects of early monocular enucleation on cortical spreading depression in well-nourished and malnourished adult rats.

Sensory development is a complex process that can influence physiological and pathological factors. In laterally-eyed mammals, monocular enucleation (ME) during development and the subsequent lack of external sensory stimuli can result in permanent morphological and physiological changes. Malnutrition, especially in early life, also can cause permanent morphofunctional changes due to inadequate nutrient intake in both hemispheres. This study investigated the effects of early (postnatal day 7) ME and malnutrition during the suckling period on cortical excitability in adulthood (110-140 days of life). For this, we compared the speed propagation of cortical spreading depression in the occipital and parietal cortex of malnourished and well-nourished adult rats, previously suckled small-sized litters with three pups (L3/dam) medium-sized litters with six pups (L6/dam), and large-sized litters with twelve pups (L12/dam). The CSD velocity was augmented by the ME in the contralateral side of the removed eye in the parietal and occipital cortex. These findings suggest that visual sensory input deprivation is associated with permanent functional changes in the visual pathways, which can alter cortical excitability and lead to modifications in CSD propagation.

Air pollution induces morpho-functional, biochemical and biomechanical vascular dysfunction in undernourished rats.

Air pollution (gases and particulate matter -PM) and child undernutrition are globally recognized stressors with significant consequences. PM and its components breach the respiratory alveolar-capillary barrier, entering the vasculature transporting not only harmful particles and its mediators but, altering vascular paracrine and autocrine functions. The aim of this study was to investigate the effects of Residual Oil Fly Ash (ROFA), on the vasculature of young animals with nutritional growth retardation (NGR). Weanling rats were fed a diet restricted 20% (NGR) compared to ad libitum intake (control-C) for 4 weeks. Rats were intranasally instilled with 1 mg/kg BW of ROFA. After 24h exposure, histological and immunohistochemical, biochemical and contractile response to NA/ACh were evaluated in aortas. ROFA induced changes in the tunica media of the aorta in all groups regarding thickness, muscular cells and expression of Connexin-43. ROFA increased TGF-ß1 and decreased eNOs levels and calcium channels in C and NGR animals. An increment in cytokines IL-6 and IL-10 was observed in C, with no changes in NGR. ROFA exposure altered the vascular contractile capacity. In conclusion, ROFA exposure could increase the risk for CVD through the alteration of vascular biochemical parameters, a possible step of the endothelial dysfunction.

Stress response to social isolation followed by exposure to a novel object in aged ewes born to undernourished mothers.

Fetal programming by subnutrition affects offspring's behaviour, metabolism, and sensitivity to stressors in sheep. The objective was to determine the stress response of ewes born to mothers nutritionally restricted during gestation to social isolation followed by exposure to a novel object. Twenty-six-year-old Corriedale ewes born to mothers who grazed high or low pasture allowances (HPA and LPA groups) from 23 days before conception until 122 days of gestation were used. Ewes were individually isolated in a novel place for 10 min, and 5 min after its beginning, an orange ball was dropped into the test pen. The ewes' behaviours were recorded during the test. Blood proteins, glucose and cortisol concentrations, heart and respiratory rates and rectal and surface temperatures were determined. The number of times looking at the ball tended to be greater in HPA ewes than LPA (6.7 ± 1.0 vs 4.7 ± 0.8, P = 0.08). The LPA ewes had greater serum albumin concentration than HPA ewes (3.2 ± 0.1 g/dL vs 3.0 ± 0.1 g/dL, P = 0.02), regardless of the applied stressors. Overall, the nutritional treatments applied to ewes during their intrauterine development did not modify the stress responses to social isolation followed by exposure to a novel object.

Combined effect of inflammation and malnutrition for long-term prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cohort study.

BACKGROUND: Inflammation is a key driver of atherosclerotic diseases and is often accompanied by disease-related malnutrition. However, the long-term burden of dysregulated inflammation with superimposed undernutrition in patients with acute coronary syndrome (ACS) remains unclear. This study sought to investigate the double burden and interplay of inflammation and malnutrition in patients with ACS undergoing percutaneous Coronary Intervention (PCI). METHODS: We retrospectively included 1,743 ACS patients undergoing PCI from June 2016 through November 2017 and grouped them according to their baseline nutritional and inflammatory status. Malnutrition was determined using the nutritional risk index (NRI) with a score lower than 100 and a high-inflamed condition defined as hs-CRP over 2 mg/L. The primary outcome was major adverse cardiovascular events (MACEs), compositing of cardiac mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Long-term outcomes were examined using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding. The reclassification index (NRI)/integrated discrimination index (IDI) statistics estimated the incremental prognostic impact of NRI and hs-CRP in addition to the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: During a median follow-up of 30 months (ranges 30-36 months), 351 (20.1%) MACEs occurred. Compared with the nourished and uninflamed group, the malnourished and high-inflamed group displayed a significantly increased risk of MACEs with an adjusted hazard ratio of 2.446 (95% CI: 1.464-4.089; P < 0.001). The prognostic implications of NRI were influenced by patients' baseline inflammatory status, as it was only associated with MACEs among those high-inflamed (P for interaction = 0.005). Incorporating NRI and hs-CRP into the GRACE risk score significantly improved its predictive ability for MACEs (NRI: 0.210, P < 0.001; integrated discrimination index; IDI: 0.010, P < 0.001) and cardiac death (NRI: 0.666, P < 0.001; IDI: 0.023, P = 0.002). CONCLUSIONS: Among patients with ACS undergoing PCI, the double burden of inflammation and malnutrition signifies poorer outcomes. Their prognostic implications may be amplified by each other and jointly improve the GRACE risk score's risk prediction performance.

Dietary characteristics of community-dwelling older adults with poor appetite: a cross-sectional analysis.

RATIONALE: Poor appetite is considered a key factor in the development of malnutrition, a link that can be explained by alterations in dietary intake. Given the limited data on dietary characteristics in community-dwelling older adults with poor appetite, the present study aimed to examine whether poor appetite is associated with lower nutrient intake and more unfavourable food choices. METHODS: In 569 participants of the Longitudinal Aging Study Amsterdam aged ≥70 years appetite was assessed using the Simplified Nutritional Appetite Questionnaire and dichotomised into normal (>14) and poor (≤14). Intake of energy, 19 nutrients, 15 food groups, the Dutch Healthy Diet Index 2015 (DHD15) and Mediterranean Diet Score (MDS) were calculated from a food frequency questionnaire. Dietary differences between appetite groups were examined using Mann-Whitney U test and binary logistic regression adjusted for potential confounders. RESULTS: Mean age was 78 ± 6 years and 52% were female. Appetite was poor in 12.5% of participants. Energy intake was 1951 (median; quartiles 1-3: 1,653-2,384) kcal/day with no difference between appetite groups. Poor appetite was associated with lower intake of protein (OR 0.948, 95%CI 0.922-0.973), folate (0.981, 0.973-0.989), zinc (0.619, 0.454-0.846), vegetables (0.988, 0.982-0.994) and lower scores of DHD15 (0.964, 0.945-0.983) and MDS (0.904, 0.850-0.961), as well as higher intake of carbohydrates (1.015, 1.006-1.023), and vitamins B2 (4.577, 1.650-12.694) and C (1.013, 1.005-1.021). CONCLUSIONS: Community-dwelling older adults with poor appetite showed poorer diet quality with a lower intake of protein, folate, zinc and vegetables, compared with those reporting normal appetite and should be advised accordingly.

Relationship between altered taste and smell with malnutrition among hemodialysis patients.

INTRODUCTION: Alterations in taste and smell are among the most distressing symptoms experienced by haemodialysis patients. There is limited research on the relationship between these two symptoms and malnutrition in haemodialysis patients. This study aimed to investigate alterations in taste and smell in hemodialysis patients and their relationship with malnutrition. METHODS: This cross-sectional study was carried out with 149 hemodialysis patients at the dialysis centers of three state hospitals. The Taste and Smell Dysfunction Questionnaire was used to assess the changes in patients' taste and smell, and the Prognostic Nutritional Index (PNI), as well as the Controlling Nutritional Status (CONUT) tool, were utilized to evaluate their nutritional status. FINDINGS: A substantial percentage (45.6%) of patients reported an altered sense of smell, and 40.2% reported an altered sense of taste. The aspect of taste that was most abnormal was bitterness (46.7%); 53.0% of the patients were at moderate risk of malnutrition by PNI score, and 14.8% were categorized as malnourished by CONUT score. Malnutrition was related to dialysis vintage: a 1-year increase in vintage was associated with an increased risk of malnutrition (OR: 1.17, 95% CI 1.02-1.32, p < 0.001). Altered taste was associated with malnutrition: one-unit increase in the standard deviation of the taste subdimension score was associated with a relative risk of malnutrition (OR: 6.89, 95% CI 1.67-28.39, p < 0.001). A one-unit increase in the standard deviation of the smell subdimension was associated with relative risk of malnutrition (OR: 1.35, 95% CI 1.10-1.64, p < 0.001). DISCUSSION: Malnutrition was found in a significantpercentage of hemodialysis patients. Altered taste and smell and the durationof dialysis treatment were significantly associated with malnutrition scores It isrecommended that healthcare professionals regularly assess alterations in tasteand smell in hemodialysis patients, as these alterations may be associated withmalnutrition, and manage these alterations accordingly.

Prevalence and prognostic significance of malnutrition in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge repair.

BACKGROUND: Malnutrition is associated with poor prognosis in several cardiovascular diseases; however, its role in patients with secondary mitral regurgitation (SMR) is poorly known. AIMS: To evaluate the impact of nutritional status, assessed using different scores, on clinical outcomes in patients with SMR undergoing transcatheter edge-to-edge repair (TEER) in a real-world setting. METHODS: A total of 658 patients with SMR and complete nutritional data were identified from the MIVNUT registry. Nutritional status has been assessed using controlling nutritional status index (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) scores. Outcomes of interest were all-cause mortality and all-cause mortality or heart failure (HF) hospitalization. RESULTS: Any malnutrition grade was observed in 79.4%, 16.7%, and 47.9% of patients by using CONUT, PNI, and GNRI, respectively, while moderate to severe malnutrition was noted in 24.7%, 16.7%, and 25.6% of patients, respectively. At a median follow-up of 2.2 years, 212 patients (32.2%) died. Moderate-severe malnutrition was associated with a higher rate of all-cause mortality (HR: 2.46 [95% CI: 1.69-3.58], HR: 2.18 [95% CI: 1.46-3.26], HR: 1.97 [95% CI: 1.41-2.74] for CONUT, PNI, and GNRI scores, respectively). The combined secondary endpoint of all-cause mortality and HF rehospitalization occurred in 306 patients (46.5%). Patients with moderate-severe malnutrition had a higher risk of the composite endpoint (HR: 1.56 [95% CI: 1.20-2.28], HR: 1.55 [95% CI: 1.01-2.19], HR: 1.36 [95% CI: 1.02-1.80] for CONUT, PNI, and GNRI scores, respectively). After adjustment for multiple confounders, moderate-severe malnutrition remained independently associated with clinical outcomes. CONCLUSIONS: Moderate-severe malnutrition was common in patients with SMR undergoing TEER. It was independently associated with poor prognosis regardless of the different scores used.

EEG functional connectivity as a Riemannian mediator: An application to malnutrition and cognition.

Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.

Prognostic value of geriatric nutritional risk index in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. METHODS: This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. RESULTS: The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI < 98 group (HR 0.04, 95% CI 0.00, 0.89). ROC analysis showed that the baseline GNRI had a very high predictive performance for all-cause death (AUC = 0.8844), and the predictive threshold was 98.62; additionally, in the RCS regression analysis and piecewise linear regression analysis we found that the threshold point for the GNRI-related all-cause death risk was 98.28 and the risk will be significantly reduced when the subjects' baseline GNRI was greater than 98.28. CONCLUSIONS: GNRI level at admission was an independent predictor of all-cause death in SCAD patients after PCI, and GNRI equal to 98.28 may be a useful threshold for nutritional intervention in SCAD patients treated with PCI.

The infant gut microbiome and cognitive development in malnutrition.

Malnutrition affects 195 million children under the age of five worldwide with long term effects that include impaired cognitive development. Brain development occurs rapidly over the first 36 months of life. Whilst seemingly independent, changes to the brain and gut microbiome are linked by metabolites, hormones, and neurotransmitters as part of the gut-brain axis. In the context of severe malnutrition, the composition of the gut microbiome and the repertoire of biochemicals exchanged via the gut-brain axis vary when compared to healthy individuals. These effects are primarily due to the recognized interacting determinants, macro- and micronutrient deficiencies, infection, infestations and toxins related to poor sanitation, and a dearth of psycho-social stimulation. The standard of care for the treatment of severe acute malnutrition is focused on nutritional repletion and weight restoration through the provision of macro- and micronutrients, the latter usually in excess of recommended dietary allowances (RDA). However, existing formulations and supplements have not been designed to specifically address key recovery requirements for brain and gut microbiome development. Animal model studies indicate that treatments targeting the gut microbiome could improve brain development. Despite this, research on humans targeting the gut microbiome with the aim of restoring brain functionality are scarce. We conclude that there is a need for assessment of cognition and the use of various tools that permit visualization of the brain anatomy and function (e.g., Magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRS), electroencephalogram (EEG)) to understand how interventions targeting the gut microbiome impact brain development.

The role of the nutrition in malnourished cancer patients: Revisiting an old dilemma.

BACKGROUND & AIMS: GLIM definition of malnutrition is recognised all over the world and, when is referring to cancer, it specifies that weight or muscle loss are associated with an inflammatory status. However, the real-world practice shows that GLIM definition cannot encompass all the wide and heterogenous clinical presentations of cancer patients with malnutrition, which involves many other drivers beyond inflammation. Moreover, placing an excessive emphasis on the inflammation can overshadow, in the clinical practice, the role of the nutritional support in malnourished cancer patients. The aim of this paper is not to criticize the rationale of the GLIM definition of cancer cachexia, but to show the complexity and heterogeneity of malnutrition of cancer patients and reasons why nutritional support should deserve such a better consideration among the oncologists. METHODS: Literature pertinent to pathophysiology of malnutrition of cancer patients is scrutinised and reasons for the frequent underuse of nutritional support are critically analysed. RESULTS: The appraisal of the literature shows that there are various pathophysiological patterns of malnutrition among cancer patients and inflammatory markers are not universally present in weight-losing cancer patients. Inflammation alone does not account for weight loss in all cancer patients and factors other than inflammation can drive hypophagia and weight loss, and hypophagia appears to be a primary catalyst for weight loss. Furthermore, malnutrition may be the consequence of the presence of several Nutrition Impact Symptoms or of the oncologic therapy. The nutritional support may fail to show benefits in malnourished cancer patients because the golden standard to validate a therapy relies on RCT, but it is ethically impossible to have an unfed control group of malnourished patients. Furthermore, nutritional interventions often fell short of the optimal standards, adherence to treatment plans was often poor, nutritional support was mainly reserved for very advanced patients and the primary endpoints of the studies on nutritional support were sometimes unrealistic. CONCLUSION: There is a gap between the suggestion of the guidelines which advocate the use of nutritional support to improve the compliance of patients facing intensive oncologic treatments or to prevent an early demise when patients enter a chronic phase of slow nutritional deterioration, and the poor use of nutrition in the real-world practice. This requires a higher level of awareness of the oncologists concerning the reasons for the lacking evidence of efficacy of the nutritional support and an understanding of its potential contribute to improve the outcome of the patients. Finally, this paper calls for a change of the oncologist's approach to the cancer patient, from only focusing on the cure of the tumour to taking care of the patient as a whole.

Gut microbiota in regulation of childhood bone growth.

Childhood stunting and wasting, or decreased linear and ponderal growth associated with undernutrition, continue to be a major global public health challenge. Although many of the current therapeutic and dietary interventions have significantly reduced childhood mortality caused by undernutrition, there remain great inefficacies in improving childhood stunting. Longitudinal bone growth in children is governed by different genetic, nutritional and other environmental factors acting systemically on the endocrine system and locally at the growth plate. Recent studies have shown that this intricate interplay between nutritional and hormonal regulation of the growth plate could involve the gut microbiota, highlighting the importance of a holistic approach in tackling childhood undernutrition. In this review, I focus on the mechanistic insights provided by these recent advances in gut microbiota research and discuss ongoing development of microbiota-based therapeutics in humans, which could be the missing link in solving undernutrition and childhood stunting.

Growing up: A NOD2 our microbes.

In a recent report in Science, Schwarzer and colleagues demonstrate the growth benefits of treatment with Lactiplantibacillus plantarum strain WJL in a preclinical mouse model of chronic undernutrition. L. plantarum influences the somatotropic axis to promote growth through intestinal epithelial NOD2 sensing.

Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.