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Approximately 30% of patients with epilepsy are drug-refractory. There is an urgent need to elucidate the exact pathophysiology of different types of epilepsies and the mechanisms of action of both antiseizure medication and metabolic therapies to treat patients more effectively and safely. For example, it has been demonstrated that exogenous ketone supplement (EKS)-generated therapeutic ketosis, as a metabolic therapy, may decrease epileptic activity in both animal models and humans, but its exact mechanism of action is unknown. However, it was demonstrated that therapeutic ketosis, among others, can increase adenosine level, which may enhance activity of A1 adenosine receptors (A1Rs) in the brain. It has also been demonstrated previously that adenosine has anti-epileptic effect through A1Rs in different models of epilepsies. Thus, it is possible that (i) therapeutic ketosis generated by the administration of EKSs may exert its anti-epileptic effect through, among other mechanisms, increased adenosine level and A1R activity and that (ii) the enhanced activity of A1Rs may be a necessary anti-epileptic mechanism evoked by EKS administration-generated ketosis. Moreover, EKSs can evoke and maintain ketosis without severe side effects. These results also suggest that the therapeutic application of EKS-generated ketosis may be a promising opportunity to treat different types of epilepsies. In this literature review, we specifically focus on the putative role of A1Rs in the anti-epileptic effect of EKS-induced ketosis. [ABSTRACT FROM AUTHOR]

This document contains a collection of abstracts from various studies on bipolar disorder. The studies cover a range of topics, including the effects of medication on cardioprotection, the impact of stress on motivation and sociability, the presence of narcissistic personality features in bipolar depression, and the development of self-report inventories to assess (hypo)manic cognitions. Other studies explore causal pathways to psychosocial functioning, methods for predicting relapses, and genetic networks in different subtypes of bipolar disorder. These abstracts provide valuable insights into the understanding and management of bipolar disorder. [Extracted from the article]

This article discusses a rare form of diabetes called maturity-onset diabetes of the young type 6 (MODY6), which is caused by a mutation in the NEUROD1 gene. The article presents a case study of a 21-year-old Chinese woman who was initially misdiagnosed with type 1 diabetes but was later diagnosed with MODY6 after genetic testing revealed a novel heterozygous NEUROD1 mutation. The article explains the molecular mechanisms behind MODY6 and discusses the clinical manifestations, diagnosis, and treatment options for this condition. The authors emphasize the importance of genetic testing in accurately diagnosing MODY6 and guiding personalized treatment. [Extracted from the article]

Key Clinical Message: High‐dose acarbose may increase the risk of diabetic ketosis/diabetic ketoacidosis in Asian patients on sodium‐glucose cotransporter‐2 inhibitors. Healthcare providers and patients should be cautious to avoid this combination. Low‐calorie diets should be avoided in patients receiving sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors to decrease the risk of diabetic ketoacidosis (DKA). High‐dose acarbose can decelerate carbohydrate absorption. We detail three cases of diabetic ketosis (DK) following concurrent SGLT‐2 inhibitor and high‐dose acarbose therapy (acarbose 300 mg/day and dapagliflozin 10 mg/day). Patients, aged 38–63 years with 3–10 years of type 2 diabetes mellitus (T2DM), developed DK, indicated by moderate urinary ketones and high glucose (urine ketone 2+ to 3+ and glucose 3+ to 4+) without acidosis, within 4 days to 1 month post‐therapy initiation. Serum glucose was 172.8–253.8 mg/dL; HbA1c was 9.97%–10.80%. The combination therapy was halted, and DK was managed with low‐dose intravenous insulin and fluids, followed by intensive insulin therapy. High‐dose acarbose with SGLT‐2 inhibitors may increase the risk of DK/DKA in Asian patients. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is marked by a substantial decrease in carbohydrate intake and an elevated consumption of fats and proteins, leading to a metabolic state referred to as "ketosis," where fats become the primary source of energy. Recent research has underscored the potential advantages of the KD in mitigating the risk of various illnesses, including type 2 diabetes, hyperlipidemia, heart disease, and cancer. The macronutrient distribution in the KD typically entails high lipid intake, moderate protein consumption, and low carbohydrate intake. Restricting carbohydrates to below 50 g/day induces a catabolic state, prompting metabolic alterations such as gluconeogenesis and ketogenesis. Ketogenesis diminishes fat and glucose accumulation as energy reserves, stimulating the production of fatty acids. Neurodegenerative diseases, encompassing Alzheimer's disease, Parkinson's disease are hallmarked by persistent neuroinflammation. Evolving evidence indicates that immune activation and neuroinflammation play a significant role in the pathogenesis of these diseases. The protective effects of the KD are linked to the generation of ketone bodies (KB), which play a pivotal role in this dietary protocol. Considering these findings, this narrative review seeks to delve into the potential effects of the KD in neuroinflammation by modulating the immune response. Grasping the immunomodulatory effects of the KD on the central nervous system could offer valuable insights into innovative therapeutic approaches for these incapacitating conditions. [ABSTRACT FROM AUTHOR]

The prevalence of nonalcoholic fatty liver disease (NAFLD) is likely to be approaching 38% of the world's population. It is predicted to become worse and is the main cause of morbidity and mortality due to hepatic pathologies. It is particularly worrying that NAFLD is increasingly diagnosed in children and is closely related, among other conditions, to insulin resistance and metabolic syndrome. Against this background is the concern that the awareness of patients with NAFLD is low; in one study, almost 96% of adult patients with NAFLD in the USA were not aware of their disease. Thus, studies on the therapeutic tools used to treat NAFLD are extremely important. One promising treatment is a well-formulated ketogenic diet (KD). The aim of this paper is to present a review of the available publications and the current state of knowledge of the effect of the KD on NAFLD. This paper includes characteristics of the key factors (from the point of view of NAFLD regression), on which ketogenic diet exerts its effects, i.e., reduction in insulin resistance and body weight, elimination of fructose and monosaccharides, limitation of the total carbohydrate intake, anti-inflammatory ketosis state, or modulation of gut microbiome and metabolome. In the context of the evidence for the effectiveness of the KD in the regression of NAFLD, this paper also suggests the important role of taking responsibility for one's own health through increasing self-monitoring and self-education. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Ketosis, a commonly observed energy metabolism disorder in dairy cows during the peripartal period, is distinguished by increased concentrations of BHB in the blood. This condition has a negative impact on milk production and quality, causing financial losses. An untargeted metabolomics approach was performed on plasma samples from cows between 5 and 7 DIM diagnosed as controls (CON; BHB <1.2 m M , n = 30), subclinically ketotic (SCK; 1.2 < BHB <3.0 m M , n = 30), or clinically ketotic (CK; BHB >3.0 m M , n = 30). Cows were selected from a commercial farm of 214 Holstein cows (average 305-d yield in the previous lactation of 35.42 ± 7.23 kg/d; parity, 2.41 ± 1.12; BCS, 3.1 ± 0.45). All plasma and milk samples (n = 90) were subjected to liquid chromatography-MS-based metabolomic analysis. Statistical analyses were performed using GraphPad Prism 8.0, MetaboAnalyst 4.0, and R version 4.1.3. Compared with the CON group, both SCK and CK groups had greater milk fat, freezing point, and fat-to-protein ratio, as well as lower milk protein, lactose, solids-not-fat, and milk density. Within 21 d after calving, compared with CON, the SCK group experienced a reduction of 2.65 kg/d in milk yield, while the CK group experienced a decrease of 7.7 kg/d. Untargeted metabolomics analysis facilitated the annotation of a total of 5,259 and 8,423 metabolites in plasma and milk. Differentially affected metabolites were screened in CON versus SCK, CON versus CK, and SCK versus CK (unpaired t -test, false discovery rate <0.05; and absolute value of log(2)-fold change >1.5). A total of 1,544 and 1,888 differentially affected metabolites were detected in plasma and milk. In plasma, glycerophospholipid metabolism, pyrimidine metabolism, tryptophan metabolism, sphingolipid metabolism, amino sugar and nucleotide sugar metabolism, phenylalanine metabolism, and steroid hormone biosynthesis were identified as important pathways. Weighted gene co-expression network analysis (WGCNA) indicated that tryptophan metabolism is a key pathway associated with the occurrence and development of ketosis. Increases in 5-hydroxytryptophan and decreases in kynurenine and 3-indoleacetic acid in SCK and CK were suggestive of an impact at the gut level. The decrease of most glycerophospholipids indicated that ketosis is associated with disordered lipid metabolism. For milk, pyrimidine metabolism, purine metabolism, pantothenate and CoA biosynthesis, amino sugar and nucleotide sugar metabolism, nicotinate and nicotinamide metabolism, sphingolipid metabolism, and fatty acid degradation were identified as important pathways. The WGCNA indicated that purine and pyrimidine metabolism in plasma was highly correlated with milk yield during the peripartal period. Alterations in purine and pyrimidine metabolism characterized ketosis, with lower levels of these metabolites in both milk and blood underscoring reduced efficiency in nitrogen metabolism. Our results may help to establish a foundation for future research investigating mechanisms responsible for the occurrence and development of ketosis in peripartal cows. [ABSTRACT FROM AUTHOR]

Since the initial description of glucose transporter-1 deficiency syndrome (Glut1-DS) the phenotype of the condition has expanded, even leading to the recognition of atypical manifestations. We report on eight patients with Glut1-DS who experienced at least one episode of acute focal neurological deficits. We conducted a retrospective analysis, collecting clinical, electrophysiological, neuroradiological, and genetic information. We focused in particular on three well-documented cases. Among 42 patients with Glut1-DS, eight individuals aged between six and 38 years presented with an acute onset of neurological disturbances: dysarthria/aphasia, oral dyskinesia, swallowing difficulties, paresthesia, facial palsy, hemi/monoplegia, vomiting, headache, and behavioral disturbances. When performed, magnetic resonance imaging (MRI) revealed signs of venous congestion and hypoperfusion and electroencephalography showed focal contralateral slowing. Deficits were transient in all patients but one. Four patients (50%) were on a ketogenic diet (KD), and two of these patients had lower than usual ketonemia levels during the episode. In two patients, MRI demonstrated the presence of an ischemic brain lesion. In Glut1-DS, stroke-like episodes are a recurrent manifestation, particularly during early adulthood, and they were reported in 19% of the patients in our cohort. Stroke mimics should be considered a key feature of Glut1-DS, as other paroxysmal disorders. It remains to be established whether a KD can prevent the recurrence of episodes and, if so, at what level of ketosis. Further observations are needed to confirm the correlation between Glut1-DS and ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Our bodies have adaptive mechanisms to fasting, in which glycogen stored in the liver and muscle protein are broken down, but also lipid mobilisation is triggered. As a result, glycerol and fatty acids are released into the bloodstream, increasing the production of ketone bodies in liver. However, there are limited studies on the incidence of perioperative urinary ketosis, the intraoperative blood glucose changes and metabolic acidosis after fasting for surgery in non‐diabetic adult patients. Methods: We conducted a retrospective cohort study involving 1831 patients undergoing gynecologic surgery under general anesthesia from January to December 2022. Ketosis was assessed using a postoperative urine test, while blood glucose levels and acid–base status were collected from intraoperative arterial blood gas analyses. Results: Of 1535 patients who underwent postoperative urinalysis, 912 (59.4%) patients had ketonuria. Patients with ketonuria were younger, had lower body mass index, and had fewer comorbidities than those without ketonuria. After adjustments, younger age, higher body mass index and surgery starting late afternoon were significant risk factors for postoperative ketonuria. Of the 929 patients assessed with intraoperative arterial blood gas analyses, 29.0% showed metabolic acidosis. Multivariable logistic regression revealed that perioperative ketonuria and prolonged surgery significantly increased the risk for moderate‐to‐severe metabolic acidosis. Conclusion: Perioperative urinary ketosis and intraoperative metabolic acidosis are common in patients undergoing gynecologic surgery, even with short‐term preoperative fasting. The risks are notably higher in younger patients with lower body mass index. Optimization of preoperative fasting strategies including implementation of oral carbohydrate loading should be considered for reducing perioperative metabolic derangement due to ketosis. [ABSTRACT FROM AUTHOR]

Animal welfare is of increasing importance, with consumers preferring animal products made with ethical practices due to growing awareness. This shift highlights the need for reliable methods to evaluate welfare. This systematic review aims to assess the validity of current animal-based welfare indicators for dairy cows to aid farmers and agricultural professionals in evaluating and improving welfare amidst the lack of a clear legislative definition. The literature search spanned five databases: CAB Direct, PubMed, Scopus, Google Scholar and Livivo, covering publications in English and German from 2011 to 2021. Specific search terms were employed, and abstracts were screened for relevance. Publications were categorized based on exclusion criteria, with a final verification process conducted by three independent scientists. Research highlights correlations between welfare measures, farm characteristics and innovative indicators like hair cortisol concentration. Farming systems and housing methods significantly affect welfare, with pasture-based systems generally resulting in reduced lameness and improved behavior. Proper housing design and management practices are important, as they influence indicators like lameness and cleanliness. Heart rate variability and heart rate monitoring provide insights into dairy cow stress levels during milking and other stressors, making them valuable for welfare assessment. Biomarker research emphasizes the need to balance productivity and health in breeding strategies, as high milk production alone does not indicate good welfare. Behavioral studies and the human-animal relationship are key to understanding welfare. Precision Livestock Farming offers real-time assessment capabilities, although validation is needed. Stress physiology is complex, and while cortisol measurement methods are promising, further research is necessary. Assessment tools like the Animal Needs Index and routine herd data analysis are valuable for identifying welfare concerns. Key findings highlight the WQ® protocol’s effectiveness and versatility, the challenge of its time demands, and the DCF protocol’s promise for more practical and efficient welfare assessments. Commercial animal welfare audits should prioritize easily observable indicators and herd records due to logistical constraints in measuring biomarkers or heart rate variability. This focus on easily accessible indicators, such as body condition score, lameness, claw health, cleanliness, and somatic cell count allows effective welfare assessments, enabling prompt action to enhance wellbeing. [ABSTRACT FROM AUTHOR]

Introduction Case Presentation Discussion and Conclusions γ‐hydroxybutyrate (GHB) is a GABA‐B agonist that rapidly produces effects that are likened to both alcohol and MDMA/ecstasy. GHB use can lead to neuroadaptation with a characteristic withdrawal syndrome. There is currently a paucity of data on the progression of GHB withdrawal, however, due to the drug's short half‐life it is generally considered to be typically 5–7 days, although some cases can be severe and complicated by life threatening delirium. Here, we present a case of severe GHB withdrawal, which recurred on multiple occasions over 56 days, despite initial clinical stabilisation on each occasion and toxicological evidence of abstinence from GHB between episodes.A male patient in his 30s presented with agitated delirium on a background of severe GHB use disorder with a 15‐year history of daily high dose GHB use. Following 3 hospital admissions over 8 weeks, all requiring intravenous sedation and tracheal intubation, the patient's withdrawal delirium was successfully treated with a slow benzodiazepine and baclofen wean over a period of 6 months. Relapse to GHB use between hospitalisations was excluded toxicologically via blood analysis performed at an institute of forensic pathology.This case highlights that GHB withdrawal can be more prolonged than previously reported in the literature and in some cases may require slow and prolonged tapering of treatment to prevent re‐emergence of delirium. Similar to previous case reports, benzodiazepines and GABA‐B receptor agonists appear to be appropriate drug classes to manage GHB withdrawal. [ABSTRACT FROM AUTHOR]

Metabolic adaptations to negative energy balance, as well as lipomobilization, influence inflammatory responses, immune function, and oxidative stress in animals. This study aimed to evaluate the biochemical profile of Mediterranean buffaloes with different levels of lipomobilization from the prepartum to the postpartum period. A total of 76 Mediterranean buffaloes were enrolled, and a weekly blood sample was taken from 7 weeks before to 6 weeks after calving. The concentration of non-esterified fatty acids (NEFAs) was determined in serum and was used to categorize buffaloes into three lipomobilization groups 7 weeks before calving: mild (NEFA-I; NEFA ≤ 0.29 mEq/L; n = 18), medium (NEFA-II; 0.29 < NEFA < 0.57mEq/L; n = 20), and severe (NEFA-III; NEFA ≥ 0.57mEq/L; n = 38). Two-way repeated measures ANOVA was used to assess changes within and between the groups and over time. Significant differences were found in the concentration levels of NEFA, β-hydroxybutyrate, glucose, cholesterol, protein profile, oxygen radicals, antioxidants, lysozyme, complement, and minerals. These results suggest that both medium and severe lipomobilization groups are associated with metabolic alterations. In conclusion, buffaloes with higher NEFA levels (>0.29mEq/L; NEFA-II and NEFA-III) at 7weeks before calving should be monitored more closely to reduce the risk of metabolic diseases. Furthermore, the medium (NEFA-II) and severe (NEFA-III) lipomobilization groups could be associated with differences in the animals' ability to manage their metabolic status. Specifically, the severe mobilization group was most associated with a greater energy deficit during both the prepartum and postpartum periods without oxidative stress. On the contrary, the medium mobilization group was associated with a less severe energy deficit but was also associated with an inflammatory status and oxidative stress during the prepartum period. These distinctions highlight the need for tailored management strategies to address varying levels of metabolic stress in dairy buffaloes. [ABSTRACT FROM AUTHOR]

Summary Alzheimer's disease (AD) is a degenerative brain disorder and the most common form of dementia. AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid‐β (Aβ) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive Aβ and tau pathology, with evidence suggesting the nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase‐1 activation and secretion of IL‐1β and IL‐18. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and β‐hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD. [ABSTRACT FROM AUTHOR]

Diet largely impacts the gut microbiota, and may affect mental and somatic health via the gut-brain axis. As such, the relationship between diet and the microbiota in Bipolar Disorder (BD) could be of importance, but has not been studied before. The aim was therefore to assess whether dietary quality is associated with the gut microbiota diversity in patients with recently diagnosed BD, and whether changes occur in dietary quality and microbiota diversity during their first year of treatment. Seventy recently (<1 year) diagnosed patients with BD were included in the "Bipolar Netherlands Cohort" (BINCO), and a total of 45 participants were assessed after one year. A 203-item Food Frequency Questionnaire (FFQ) data yielded the Dutch Healthy index (DHD-15), and the microbiota composition and diversity of fecal samples were characterized by 16S rRNA gene amplicon sequencing at baseline and 1-year follow-up. Associations and changes over time were analyzed using multivariate regression analyses and t -tests for paired samples. Included patients had a mean age of 34.9 years (SD ± 11.2), and 58.6 % was female. Alpha diversity (Shannon diversity index), richness (Chao1 index) and evenness (Pielou's Evenness Index) were positively associated with the DHD-15 total score, after adjustment for sex, age and educational level (beta = 0.55; P < 0.001, beta = 0.39; P = 0.024, beta = 0.54; P = 0.001 respectively). The positive correlations were largely driven by the combined positive effect of fish, beans, fruits and nuts, and inverse correlations with alcohol and processed meats. No significant changes were found in DHD-15 total score, nor in microbiota diversity, richness and evenness indexes during one year follow-up and regular treatment. A healthy and varied diet is associated with the diversity of the microbiota in BD patients. Its potential consequences for maintaining mood stability and overall health should be studied further. • A healthier diet was associated with higher diversity and richness of microbiota in recently diagnosed BD patients. • Overall dietary quality did not change significantly during one year follow-up in recently diagnosed BD patients. • Microbiota diversity did not change significantly during one year of follow-up in recently diagnosed BD patients. [ABSTRACT FROM AUTHOR]

Exogenous supplementation with ketone beverages has been shown to reduce plasma glucose levels during acute nutritional ketosis. It remains to be investigated whether growth differentiation factor 15 (GDF-15)—an anorexigenic hormone—is involved in this process. The aim was to investigate the effect of a ketone ester beverage delivering β-hydroxybutyrate (KEβHB) on plasma levels of GDF-15, as well as assess the influence of eating behaviour on it. The study was a randomised controlled trial (registered at clinicaltrials.gov as NCT03889210). Individuals were given a KEβHB beverage or placebo in a cross-over fashion. Blood samples were collected at baseline, 30, 60, 90, 120, and 150 min after ingestion. Eating behaviour was assessed using the three-factor eating questionnaire. GDF-15 levels were not significantly different (p = 0.503) after the KEβHB beverage compared with the placebo. This finding remained consistent across the cognitive restraint, emotional eating, and uncontrolled eating domains. Changes in the anorexigenic hormone GDF-15, irrespective of eating behaviour, do not appear to play a major role in the glucose-lowering effect of exogenous ketones. [ABSTRACT FROM AUTHOR]

Ketosis is currently regarded as a major metabolic disorder of dairy cows, reflective of the animal's efforts to adapt to energy deficit while transitioning into lactation. Currently viewed as a pathology by some, ketosis is associatively implicated in milk production losses and peripartal health complications that increase the risk of early removal of cows from the herd, thus carrying economic losses for dairy farmers and jeopardizing the sustainability of the dairy industry. Despite decades of intense research in the mitigation of ketosis and its sequelae, our ability to lessen its purported effects remains limited. Moreover, the association of ketosis to reduced milk production and peripartal disease is often erratic and likely mired by concurrent potential confounders. In this review, we discuss the potential reasons for these apparent paradoxes in the light of currently available evidence, with a focus on the limitations of observational research and the necessary steps to unambiguously identify the effects of ketosis on cow health and performance via controlled randomized experimentation. A nuanced perspective is proposed that considers the dissociation of ketosis—as a disease—from healthy hyperketonemia. Furthermore, in consideration of a growing body of evidence that highlights positive roles of ketones in the mitigation of metabolic dysfunction and chronic diseases, we consider the hypothetical functions of ketones as health-promoting metabolites and ponder on their potential usefulness to enhance dairy cow health and productivity. [ABSTRACT FROM AUTHOR]

Fulminant type 1 diabetes (FT1D) is a unique subtype of type 1 diabetes, characterized by acute absolute insulin deficiency, severe ketosis, and increased risk of hypoglycemia, glycemic variability and microvascular complications. Seven people with FT1D were identified from two tertiary centers in Singapore. Six were Chinese, the mean age was 35 years and all were lean (mean body mass index 20.3 kg/m2). All presented with diabetes ketosis or ketoacidosis and low C‐peptide. All but one had low glutamic acid decarboxylase antibodies. Nearly half had a missed/delayed diagnosis of FT1D. Three had frequent hypoglycemia, which improved after transition to continuous subcutaneous insulin infusion therapy. Individuals with FT1D experience unique diagnostic and management challenges associated with rapid absolute insulin deficiency. Greater awareness about this clinical entity is required. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical ketosis is a dangerous disease in the dairy industry, as it affects milk production in cows. We imply that calmodulin is abundantly expressed in adipocytes during lipolysis and inflammatory responses. Thus, reducing calmodulin levels could help control the inflammatory response in the adipose tissue of dairy cows during the development of clinical ketosis. Clinical ketosis is a detrimental metabolic disease in dairy cows, often accompanied by severe lipolysis and inflammation in adipose tissue. Our previous study suggested a 2.401-fold upregulation in the calmodulin (CaM) level in the adipose tissue of cows with clinical ketosis. Therefore, we hypothesized that CaM may regulate lipolysis and inflammatory responses in cows with clinical ketosis. To verify the hypothesis, we conducted a thorough veterinary assessment of clinical symptoms and serum β-hydroxybutyrate (BHB) concentration. Subsequently, we collected subcutaneous adipose tissue samples from six healthy and six clinically ketotic Holstein cows at 17 ± 4 days postpartum. Commercial kits were used to test the abundance of BHB, non-esterified fatty acid (NEFA), the liver function index (LFI), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α). We found that cows with clinical ketosis exhibited higher levels of BHB, NEFA, LFI, IL-6, IL-1β, TNF-α, and lower glucose levels than healthy cows. Furthermore, the abundance of CaM, toll-like receptor 4 (TLR4), inhibitor of nuclear factor κB kinase subunit β (IKK), phosphorylated nuclear factor κB p65/nuclear factor κB p65 (p-NF-κB p65/NF-κB p65), adipose triacylglycerol lipase (ATGL), and phosphorylated hormone-sensitive lipase/hormone-sensitive lipase (p-HSL/HSL) was increased, while that of perilipin-1 (PLIN1) was decreased in the adipose tissue of cows with clinical ketosis. To investigate the mechanism underlying the responses, we isolated the primary bovine adipocytes from the adipose tissue of healthy cows and induced the inflammatory response mediated by TLR4/IKK/NF-κB p65 with lipopolysaccharide (LPS). Additionally, we treated the primary bovine adipocytes with CaM overexpression adenovirus and CaM small interfering RNA. In vitro, LPS upregulated the abundance of TLR4, IKK, p-NF-κB p65, ATGL, p-HSL/HSL, and CaM and downregulated PLIN1. Furthermore, CaM silencing downregulated the abundance of LPS-activated p-HSL/HSL, TLR4, IKK, and p-NF-κB p65 and upregulated PLIN1 in bovine adipocytes, except for ATGL. However, CaM overexpression upregulated the abundance of LPS-activated p-HSL/HSL, TLR4, IKK, and p-NF-κB p65 and downregulated PLIN1 expression in bovine adipocytes. These data suggest that CaM promotes lipolysis in adipocytes through HSL and PINL1 while activating the TLR4/IKK/NF-κB inflammatory pathway to stimulate an inflammatory response. There is a positive feedback loop between CaM, lipolysis, and inflammation. Inhibiting CaM may act as an adaptive mechanism to alleviate metabolic dysregulation in adipose tissue, thereby relieving lipolysis and inflammatory responses. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to evaluate the effect of a low‐carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis. Methods: Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36‐Item Health Survey [RAND‐36], Impact of Weight on Quality of Life [IWQOL]‐Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention. Results: A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m2) were included. The LCD group had greater weight loss (−2.8 kg; 95% CI: −4.1 to −1.0; p < 0.001) and larger reduction in pain now (−1.1; 95% CI: −1.9 to −0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions. Conclusions: Diet‐induced weight loss in women with lipedema can improve QoL. An energy‐restricted LCD seems to be superior to a standard control diet in reducing pain. [ABSTRACT FROM AUTHOR]

The article provides current information regarding medical errors in diagnosing diabetes mellitus (DM), analyzes their factors, and outlines preventive measures. The causes of the most common diagnostic errors in diabetology include limited access to quality healthcare, insufficient training and number of qualified personnel, low quality of teamwork and medical information exchange, inadequate availability of diagnostic tests, poor coordination of care and follow-up, lack of medical informatics resources, human factors, and cognitive biases (such as misidentification of DM and its type, incorrect context creation, overestimation/underestimation of incidental findings, premature termination of the diagnostic process, and lack of knowledge and skills in diabetology). The most typical diagnostic discrepancies involve misidentifying type 1 DM (including latent autoimmune diabetes in adults), type 2 DM, and other specific types of DM. This is due to the increasing heterogeneity of DM, blurring of the boundaries between its types, atypical disease course, the decreased diagnostic value of the essential criteria for DM types (age, presence of metabolic syndrome signs, ketosis, dependency on insulin therapy), presence of comorbid conditions, and limited availability of diagnostic tests to specify the type of diabetes. To optimize diagnosis and prevent diagnostic errors, we have developed a Telegram bot DiaType based on a multilevel algorithm for the differential diagnosis of various types of DM. The testing of this Telegram bot has shown its high effectiveness in identifying DM variants. The advantages of DiaType include accessibility, interactivity, accuracy, and support for medical professionals, which helps improve diagnostic efficiency, simplify the diagnostic process, especially for primary care physicians, prevent diagnostic errors, and, consequently, improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Fulminant type 1 diabetes is characterized by a low prevalence of autoantibodies, and was originally described as a nonautoimmune subtype of type 1 diabetes. Herein, we report a case in which we observed the process of extremely rapid onset of diabetes and early decline in anti-glutamic acid decarboxylase (GAD) antibody titers during the inpatient stay. Case Report: A 61-year-old man was brought to our hospital with marked hyperglycemia (1327 mg/dL), ketonemia (3-hydroxybutyrate: 14 012 µmol/L), and moderately elevated HbA1c (7.2%) and glycoalbumin (22.3%). C-peptide levels were undetectable. He had suffered from thirst, polyuria, and fatigue for 2 days. Abrupt onset was proven by the clinical data when he visited the hospital with respiratory symptoms 6 days before his admission; plasma glucose, glycoalbumin, C-peptide, and insulin levels were 117 mg/dL, 13.0%, 5.07 ng/mL, and 24.4 µIU/mL, respectively. The anti-GAD antibody titer measured by enzyme-linked immunosorbent assay was 111 U/mL at admission, 22.8 U/mL 2 weeks after admission, and negative 1 year later. He had a susceptible haplotype DRB1*09: 01-DQB1*03: 03, which is significantly more common in anti-GAD antibody-positive patients with fulminant type 1 diabetes. Conclusions: The early decline of anti-GAD antibody titer likely reflected rapid and complete beta cell loss. The sequential metabolic and immunological observation in this case may provide insight into the pathogenesis of fulminant type 1 diabetes. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics the physiological state of fasting. The potential therapeutic effects in many chronic conditions have led to the gaining popularity of the KD. The KD has been demonstrated to alleviate inflammation and oxidative stress, modulate the gut microbiota community, and improve metabolic health markers. The modification of these factors has been a potential therapeutic target in serious mental illness (SMI): bipolar disorder, major depressive disorder, and schizophrenia. The number of clinical trials assessing the effect of the KD on SMI is still limited. Preliminary research, predominantly case studies, suggests potential therapeutic effects, including weight gain reduction, improved carbohydrate and lipid metabolism, decrease in disease-related symptoms, increased energy and quality of life, and, in some cases, changes in pharmacotherapy (reduction in number or dosage of medication). However, these findings necessitate further investigation through larger-scale clinical trials. Initiation of the KD should occur in a hospital setting and with strict care of a physician and dietitian due to potential side effects of the diet and the possibility of exacerbating adverse effects of pharmacotherapy. An increasing number of ongoing studies examining the KD's effect on mental disorders highlights its potential role in the adjunctive treatment of SMI. [ABSTRACT FROM AUTHOR]

Background and Aim: Biochemical blood testing is the main diagnostic indicator of the clinical condition of highly productive animals and a method of determining changes in metabolic disorders. This study focuses on metabolic changes (ketosis), which are of the utmost importance in the assessment of the health status of animals, as well as differences in intergroup characteristics. The main focus of this study is to demonstrate the influence of subclinical ketosis in highly productive cows on changes in biochemical blood parameters during different physiological periods to further prevent this disease, adjust feeding rations, and prevent premature culling of animals. This study aimed to evaluate and establish changes in the biochemical status dynamics of highly productive cows with metabolic disorders in an industrial livestock complex. Materials and Methods: Blood samples were systematically collected from highly productive cows of the Simmental breed (n = 60) and served as the primary material for subsequent analyses. Each methodological step was designed to ensure evaluation of the metabolic changes associated with post-calving adjustments in highly productive dairy cows. This study employed a comprehensive approach integrating clinical assessments, laboratory analyses, biochemical evaluations, instrumental measurements, and statistical analyses. Results: A biochemical blood test showed that the number of ketone bodies in the experimental group exceeded the norm, varied depending on the physiological state of the animals, and ranged from 0.89 to 1.45 mmol/L. At 10 days after calving, the highest indicator was 1.45 ± 0.05 mmol/L. This indicator was 1.05 mmol/L higher than that in the control group and exceeded the norm by 0.95. Conclusion: Excess ketone bodies in the blood of animals led to accumulation in urine and milk, indicating a disturbance in metabolic processes in the body and a decrease in the quality of animal husbandry products. The sample size and the focus on a single breed from one geographical location may limit the generalizability of the findings. Further research should explore the mechanistic bases of ketosis development, potentially integrating genomic and proteomic approaches to understand the genetic predispositions and molecular pathways involved. [ABSTRACT FROM AUTHOR]

Background: Global variations in epidemiology of type 1 diabetes mellitus (T1DM) exist. This study is designed to examine demographic and clinical features of T1DM over the past 3 decades as well as evolving trends in epidemiology over last 50 years. Methods: Clinical characteristics of 925 patients with T1DM over last 30 years (1990–2019) were evaluated and compared to previously published data of 477 patients diagnosed between 1969 and 1990 from one of the major referral centers for diabetes in Turkey. Results: Mean age at diagnosis decreased from 9.5 ± 4.0 to 7.1 ± 3.6 years within the past 50 years (p <.001). Age at diagnosis peaked at 12–14 years between 1969 and 1990, then fell to 10–11.9 years between 1990 and 1999, and to 4–5.9 years between 2000–2009 and 2010–2019 (p =.005). Although the percentage of patients diagnosed <6 years of age is gradually increasing, the percentage between the ages of 6 and 11.9 years is decreasing, and the percentage diagnosed ≥12 years remained stable. A total of 47.5% of patients had ketoacidosis, 38.2% had ketosis, and 14.3% had only hyperglycemia. 23% of patients had severe diabetic ketoacidosis (DKA), whereas 42% had moderate. Over last 3 decades, there has been no change in frequency of ketoacidosis at presentation, but there has been significant decline in severity (p =.865, and p <.001, respectively). Although the frequency of patients with mild DKA increased over time, frequency of patients with moderate DKA decreased; however, no significant difference was observed among patients with severe ketoacidosis. DKA was more frequent and severe in patients <6 years of age (p =.005, and p <.001, respectively). Conclusion: Age at diagnosis shifted to younger ages in T1DM in the past 50 years. Half of patients had ketoacidosis at diagnosis and frequency of presentation with DKA did not decrease, but severity decreased slightly. Increase in prevalence of T1DM in the younger age group and the fact that half of patients present with DKA indicate that awareness should be increased in terms of early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Genetic mitochondrial diseases impact over 1 in 4000 individuals, most often presenting in infancy or early childhood. Seizures are major clinical sequelae in some mitochondrial diseases including Leigh syndrome, the most common pediatric presentation of mitochondrial disease. Dietary ketosis has been used to manage seizures in mitochondrial disease patients. Mitochondrial disease patients often require surgical interventions, leading to anesthetic exposures. Anesthetics have been shown to be toxic in the setting of mitochondrial disease, but the impact of a ketogenic diet on anesthetic toxicities in this setting has not been studied. Aims: Our aim in this study was to determine whether dietary ketosis impacts volatile anesthetic toxicities in the setting of genetic mitochondrial disease. Methods: The impact of dietary ketosis on toxicities of volatile anesthetic exposure in mitochondrial disease was studied by exposing young Ndufs4(−/−) mice fed ketogenic or control diet to isoflurane anesthesia. Blood metabolites were measured before and at the end of exposures, and survival and weight were monitored. Results: Compared to a regular diet, the ketogenic diet exacerbated hyperlactatemia resulting from isoflurane exposure (control vs. ketogenic diet in anesthesia mean difference 1.96 mM, Tukey's multiple comparison adjusted p =.0271) and was associated with a significant increase in mortality during and immediately after exposures (27% vs. 87.5% mortality in the control and ketogenic diet groups, respectively, during the exposure period, Fisher's exact test p =.0121). Our data indicate that dietary ketosis and volatile anesthesia interact negatively in the setting of mitochondrial disease. Conclusions: Our findings suggest that extra caution should be taken in the anesthetic management of mitochondrial disease patients in dietary ketosis. [ABSTRACT FROM AUTHOR]

Background: The German guidelines recommend that intravenous fluid therapy should not be mandatorily performed in children with short fasting times undergoing short anesthesia, but there is a lack of clinical studies including a large number of pediatric patients. Therefore, we performed a prospective non‐interventional multicenter observational study to evaluate the perioperative hemodynamic and metabolic stability of children undergoing short anesthesia without intravenous fluid therapy. Aims: The primary aim was to assess the incidence of hypotension and the secondary aim was to assess the real preoperative fasting times, the incidence of hypoglycemia and the impact on ketone bodies and acid–base balance. Methods: Children aged 1 month–18 years undergoing short anesthesia (<1 h) without intravenous fluid therapy were enrolled. Patient demographics, the surgical or diagnostic procedure performed, anesthesia, hemodynamic, laboratory data, and adverse events were documented using a standardized case report form. Results: Four hundred and twenty seven children that were investigated at three pediatric centers from July 2021 to June 2022 (mean age 83.4 ± 58.9 months, body weight 27.9 ± 19.8 kg) were included in the analysis. The real preoperative fasting times were 14.2 ± 3.6 h for solids, 7.2 ± 3.5 h for milk and 5 ± 4.8 h for clear fluids. During the course of anesthesia, hypotension (<2.5th percentile) was detected in 3 of 427 cases (0.7%), hypoglycemia (glucose <3.0 mmol L−1) in 1 of 355 cases (0.3%), and ketosis (ketone bodies ≥0.6 mmol L−1) in 51 of 233 cases (21.9%). The occurrence of ketosis was associated with lower body weight (p <.001) and longer fasting times for solids or milk (p =.021), but not for clear fluids (p =.69). Conclusions: Our study supported the German guidelines recommendation that perioperative intravenous fluid therapy is not mandatory in children beyond the neonatal period with short pre‐ and postoperative fasting times undergoing short anesthesia (<1 h). [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is a life‑threatening condition affecting individuals with diabetes characterised by hyperglycaemia, metabolic acidosis and ketonemia. The incidence and financial burden of DKA is still high. Thiamine deficiency is well documented in patients with DKA and could be associated with cardiac dysfunction in those patients. Thiamine deficiency leads to cardiac dysfunction, neuronal death and worsens the prognosis of DKA. There is an existing metabolic relationship between thiamine deficiency in diabetes, obesity and bariatric surgery. Careful monitoring of thiamine, along with other vitamins, is essential for diabetic patients, obese individuals and postbariatric surgery. Further research and clinical studies are urgently needed to assess the following: (1) Whether diabetes, obesity and bariatric surgery make individuals more prone to have DKA related to thiamine deficiency and (2) Whether supplementation of thiamine can protect diabetic patients, obese subjects and individuals undergoing bariatric surgery from DKA. This review summarises the biochemistry of thiamine and the existing metabolic relationships between thiamine deficiency in DKA, diabetes, obesity and bariatric surgery. Primary and family physicians have an important role in ensuring adequate replacement of thiamine in individuals with diabetes, obesity and bariatric surgery. [ABSTRACT FROM AUTHOR]

Milk analysis using mid-infrared spectroscopy (MIR) is a fast and inexpensive way of examining milk samples on a large scale for fat, protein, lactose, urea and many other novel traits. A new indicator trait for ketosis, KetoMIR, which is based on clinical ketosis diagnoses and MIR-predicted traits, was developed by the Regional State Association for Performance and Quality Inspection in Animal Breeding of Baden Württemberg in 2015. The KetoMIR result is available for each cow at milk recording during the first 120 days in milk and presented to farmers in three classes: 1 = low ketosis risk, 2 = moderate ketosis risk and 3 = high ketosis risk. The aim of the current study was to analyze the phenotypic relationships between KetoMIR and milk yield, fertility and health at the herd level. Annual herd reports from 12,909 herds with an average herd size of 27 cows were available for the analyses. Overall, the mean incidence of ketosis (KetoMIR risk class 2 or 3) at the herd level was 14.0%. Farms with the lowest ketosis risk (=10% of cows in the herd with a moderate or high ketosis risk) differed in all variables from the farms with the highest ketosis risk (>50% of cows in the herd with a moderate or high ketosis risk). The increased ketosis risk based on KetoMIR was associated with lower average herd milk yield (-1,975 kg milk). Mean herd somatic cell count in first and higher lactations was increased by 60,500 and 134,400 cells/ml, respectively. The interval from calving to first service was prolonged by +36.5 days, as was the calving interval with +58.2 days. The newly developed KetoMIR trait may be used in ketosis prevention programs. [ABSTRACT FROM AUTHOR]

Introduction: The risk of ketosis is assessed by monitoring changes in plasma metabolites and cow behavior during the peripartum period. However, little is known about changes in the fecal bile acid and microbiota of cows before parturition. Therefore, this study clarified the bile acid profile and screened potential warning biomarkers in heifers 7 days before calving. Methods: Ninety healthy cows were tracked in the transition period, and plasma and feces were collected 7 days before calving, on calving day, and 7 days after calving. The cows were divided into ketosis and healthy groups based on the blood β-hydroxybutyric acid levels from day 7 after calving. The levels of serum biochemical indices were measured at three time points using commercial kits. Ten cows in the ketosis group (KET-7) and 10 healthy cows (HEA-7) were randomly selected 7 days before calving for metabolome and 16S rRNA amplicon sequencing. Results: No significant differences in serum energy-related indices were observed 7 days before calving. The major bile acids in the feces of the KET-7 group were non-conjugated secondary bile acids (UnconSBA). Differential bile acids were primarily derived from UnconSBA. The potential ketosis warning metabolite in feces for 7 days before delivery was isodeoxycholic acid. The abundance of Rikenellaaceae-RC9-gut-group in the KET-7 group increased, whereas the abundance of Oscillospiraceae UCG-010 bacteria significantly decreased. Lactobacillus and Prevotella-9 in feces were potential warning biomarkers for ketosis in dairy cows 7 days before calving. The variation in differential bile acids in the plasma, consistent with the feces, was mainly derived from UnconSBA. Lithocholic acid in the plasma was a potential ketosis warning metabolite 7 days before delivery. Conclusion: Ketotic cows experienced bile acid metabolism disorders 7 days before calving, and the gut microbiota was closely related to bile acid metabolism disorders. Future studies should investigate the relationship between secondary bile acids and the development of ketosis. [ABSTRACT FROM AUTHOR]

Background: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). Objective: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). Methods: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. Results: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. Conclusions: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. Trial Registration: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 – Sept 13, 2022. [ABSTRACT FROM AUTHOR]

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. Methods: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Results and discussion: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. Conclusions: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK. [ABSTRACT FROM AUTHOR]

Glucose transporter type 1 deficiency syndrome (GLUT-1DS) is characterized by alterations in glucose translocation through the blood–brain barrier (BBB) due to mutation involving the GLUT-1 transporter. The fundamental therapy is ketogenic diet (KD) that provide an alternative energetic substrate — ketone bodies that across the BBB via MCT-1 — for the brain. Symptoms are various and include intractable seizure, acquired microcephalia, abnormal ocular movement, movement disorder, and neurodevelopment delay secondary to an energetic crisis for persistent neuroglycopenia. KD is extremely effective in controlling epileptic seizures and has a positive impact on movement disorders and cognitive impairment. Cases of KD resistance are rare, and only a few of them are reported in the literature, all regarding seizure. Our study describes a peculiar case of GLUT-1DS due to a new deletion involving the first codon of SLC2A1 gene determining a loss of function with a resistance to KD admitted to hospital due to intractable episodes of dystonia. This patient presented a worsening of symptomatology at higher ketonemia values but without hyperketosis and showed a complete resolution of symptomatology while maintaining low ketonemia values. Our study proposes an in-silico genomic and proteomic analysis aimed at explaining the atypical response to KD exhibited by our patient. In this way, we propose a new clinical and research approach based on precision medicine and molecular modelling to be applied to patients with GLUT-1DS resistant to first-line treatment with ketogenic diet by in silico study of genetic and altered protein product. [ABSTRACT FROM AUTHOR]

Aim: A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens. Methods: Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis. Results: The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA. Conclusion: Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging. [ABSTRACT FROM AUTHOR]

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic ketoacidosis (DKA) is associated with volume depletion and hemodynamic alterations. Changes in systemic microcirculation during DKA have not been described so far. Methods: In this case report, we describe the evolution of sublingual microcirculatory changes, monitored using sidestream dark field (SDF) imaging during the treatment of severe diabetic ketoacidosis in a 13-year-old girl. The patient presented a pH of 6.84, a glycemia level of 27.2 mmol/L, a ketonemia level of 5.6 mmol/L, a base excess of −29.4 mmol/L, hypernatremia, hyperosmolality due to acute gastritis, and a malfunction of the glucose sensor. Sublingual microcirculation measurements using an SDF probe were initiated 60 min after the initiation of treatment, which was then repeated 2, 3, 4, 6, 12, and 24 h after treatment initiation, as well as on the day of discharge. Results: Substantial alterations of microvascular perfusion parameters, both total and small vessel densities, perfused vessel densities, and the DeBacker score, were observed during the first 6 to 12 h of treatment. The degree of microcirculatory alteration was strongly negatively correlated with calculated osmolality, sodium levels, ketone and lactate levels, and blood pressure values. Conclusions: DKA is, in its complexity, associated with a serious microcirculatory alteration. SDF imaging provides insight into the severity of the patient's microcirculatory alteration and its evolution during treatment. [ABSTRACT FROM AUTHOR]

Lameness is one of the greatest constraints on the productivity, health, and welfare of dairy cattle. A cross-sectional study was carried out from March 2021 to September 2021 in Hawassa town with the aim of assessing the prevalence and identifying the associated risk factors of lameness in dairy farms. The study was conducted on 440 animals belonging to 19 randomly selected intensive dairy farms. Data regarding lameness and its possible risk factors were collected both at animal and farm level using a questionnaire. The results showed that the overall prevalence of lameness was 10.2% (n = 45/440). The association of lameness prevalence with various risk factors including milking status, exercise, age, parity, milk yield, and lactation stage was statistically tested using logistic regression model. There was a significant variation in the prevalence of lameness (P < 0.05) between cattle with different milking status, age, parity, milk yield, and stage of lactation by the univariable analysis result. According to the multivariable analysis, only milk yield and lactation stage were statistically associated with the occurrence of lameness. Milking animals (8%) had higher prevalence of lameness than nonmilking (2.2%). The occurrence of lameness increased with milk yield. The highest prevalence of lameness was recorded in the early stage of lactation. Lameness was more frequent in hind limbs (6.6%) than in forelimbs (3.6%). The main causes of lameness observed in this study were both claw overgrowth 10 (2.3%), unequal claw size 10 (2.3%), solar ulcer 8 (1.8%), interdigital necrobacillosis 2 (0.5%), interdigital hyperplasia 2 (0.5%), and digital dermatitis 1 (0.2%). There was no means of early lameness diagnosis in 94.7% of farms. Lameness was found to be an important disease in dairy cows at Hawassa town. Prevention and early diagnosis leading to prompt treatment of lameness in cows should be part of dairy farm management practice. [ABSTRACT FROM AUTHOR]

This document provides an update on the definition, classification, diagnosis, and differential diagnosis of diabetes mellitus as of 2023. It includes changes in diagnostic approaches, the reliability of HbA1c in renal insufficiency, the determination of ketone bodies, and the addition of a section on differential diagnosis. The document outlines the classification of diabetes mellitus into type 1, type 2, other specific types, and gestational diabetes. It discusses the diagnostic criteria for diabetes mellitus, impaired fasting glucose, impaired glucose tolerance, and gestational diabetes. The document also highlights the importance of considering different diagnostic criteria for diabetes types and the need for quality assurance in laboratory testing. It provides information on various types of diabetes, including type 1, LADA, and MODY, and emphasizes the importance of early detection and proper diagnosis for appropriate therapy and improved outcomes. [Extracted from the article]

Upon both acute and prolonged alcohol intake, the brain undergoes a metabolic shift associated with increased acetate metabolism and reduced glucose metabolism, which persists during abstinence, putatively leading to energy depletion in the brain. This study evaluates the efficacy of ketogenic treatments to rescue psychiatric and neurochemical alterations during long-term alcohol withdrawal. Female mice were intermittently exposed to alcohol vapor or air for three weeks, during which mice were introduced to either a ketogenic diet (KD), control diet supplemented with ketone ester (KE) or remained on control diet (CD). Withdrawal symptoms were assessed over a period of four weeks followed by re-exposure using several behavioral and biochemical tests. Alcohol-exposed mice fed CD displayed long-lasting depressive-like symptoms measured by saccharin preference and tail suspension, as well as decreased norepinephrine levels and serotonin turnover in the hippocampus. Both KD and KE rescued anhedonia for up to three weeks of abstinence. KD mice showed higher latency to first immobility in the tail suspension test, as well as lower plasma cholesterol levels. Our findings show promising effects of nutritional ketosis in ameliorating alcohol withdrawal symptoms in mice. KD seemed to better rescue these symptoms compared to KE. [ABSTRACT FROM AUTHOR]

Aims: Ketosis‐prone type 2 diabetes was defined by the World Health Organization in 2019. According to the literature, the diagnosis is based on the presence of ketosis, islet autoantibody negativity and preserved insulin secretion. Our meta‐analysis assessed the prevalence and clinical characteristics of ketosis‐prone type 2 diabetes among patients hospitalised with diabetic ketoacidosis (DKA) or ketosis. Methods: The systematic search was performed in five main databases as of 15 October 2021 without restrictions. We calculated the pooled prevalence of ketosis‐prone type 2 diabetes (exposed group) within the diabetic population under examination, patients with ketoacidosis or ketosis, to identify the clinical characteristics, and we compared it to type 1 diabetes (the comparator group). The random effects model provided pooled estimates as prevalence, odds ratio and mean difference (MD) with 95% confidence intervals. Results: Eleven articles were eligible for meta‐analysis, thus incorporating 2010 patients of various ethnic backgrounds. Among patients presenting with DKA or ketosis at the onset of diabetes, 35% (95% CI: 24%–49%) had ketosis‐prone type 2 diabetes. These patients were older (MD = 11.55 years; 95% CI: 5.5–17.6) and had a significantly higher body mass index (BMI) (MD = 5.48 kg/m2; 95% CI: 3.25–7.72) than those with type 1 diabetes. Conclusions: Ketosis‐prone type 2 diabetes accounts for one third of DKA or ketosis at the onset of diabetes in adults. These patients are characterised by islet autoantibody negativity and preserved insulin secretion. They are older and have a higher BMI compared with type 1 diabetes. C‐peptide and diabetes‐related autoantibody measurement is essential to identify this subgroup among patients with ketosis at the onset of diabetes. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 43-year-old woman with a pruritic rash on her neck and back. The patient had a medical history of anorexia nervosa, herpes zoster, and peripheral neuropathy. Physical examination revealed red scaly papules that coalesced in a reticular pattern. The diagnosis was prurigo pigmentosa, a rare inflammatory disorder that is more commonly observed in young adults of Asian descent. The condition is associated with diet, particularly ketosis induced by ketogenic diets or anorexia nervosa. Treatment options include oral antibiotics, such as doxycycline, and dietary modifications. [Extracted from the article]

A 74-year-old patient with type 2 diabetes mellitus received basal-bolus insulin, insulin secretagogues, and sodium glucose transporter 2 (SGLT2) inhibitors. After immune checkpoint inhibitor treatment for lung cancer, he suffered from depressed consciousness with a urinary ketone body (3+). When all hypoglycemic treatments were discontinued, his serum blood glucose remained at 121 mg/dL. He was diagnosed with euglycemic diabetic ketosis. Endocrine loading tests revealed isolated adrenocorticotropic hormone (ACTH) deficiency as an immune-related adverse event. It was suggested that euglycemic diabetic ketosis was induced by the self-suspension of insulin and insulin secretagogues, adrenal insufficiency, SGLT2 inhibitors, and carbohydrate intake shortage. [ABSTRACT FROM AUTHOR]

Introduction: Optimizing the management of dairy cattle reproduction can reduce postpartum ovarian disease in high-yielding dairy cows and thus enhance ranch economic benefit. The hypothesis of this study was that the Double-Ovsynch (DO) protocol in high-producing dairy cows would result in a lower incidence of follicular cysts but a higher incidence of luteal cysts compared to those undergoing the Presynch-Ovsynch (PS) protocol. Methods: In this experiment, 384 cows (204 primiparous and 180 multiparous) were allocated to the DO group, which followed the protocol: GnRH-7d-PGF2α-3d-GnRH-7d-Ovsynch-56 h (GnRH-7d-PGF2α-56 h-GnRH-16hTAI), starting on 39 ± 3 days in milk (DIM). Additionally, 359 cows (176 primiparous and 183 multiparous) were assigned to the PS group, which followed the protocol: PGF2α-14d-PGF2α-12d-Ovsynch-56 h, starting on 31 ± 3 DIM. In DO, B-mode ultrasound examinations were conducted 1 day after the GnRH-7d-PGF2α-3d-GnRH protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days of suspected cases. In PS, B-mode ultrasound examinations were conducted 1 day after the PGF2α-14d-PGF2α protocol to diagnose the presence of ovarian diseases followed by reexamination after 7 days. For all cows confirmed to having ovarian diseases, a second B-mode ultrasound examination was conducted at the time of the second GnRH and timed artificial insemination (TAI). If the ovary showed a normal developing follicle in combination with normal ovulation, the ovarian disease was considered to be cured. Results: The current study revealed no significant difference in the overall incidence and cure rate of postpartum ovarian diseases between DO and PS (incidence rate: 3.9% vs. 6.7%, cure rate: 50% vs. 41.7%, DO vs. PS). Also, there was no significant difference in the incidence and cure rate of luteal cysts between DO and PS (incidence rate: 2.9% vs. 2.2%, cure rate: 50.0% vs. 50.0%). The incidence of follicular cysts was significantly lower in the DO group than in the PS group (0.8% vs. 2.8%, DO vs. PS, p = 0.037), but there was no significant difference in the cure rates (66.7% vs. 50%). The occurrence of inactive ovary was lower in DO compared to PS (0.2% vs. 1.7%, p = 0.047). There was no significant difference in the pregnancy rate between the DO and PS groups (48.2% vs. 41.8%), although the DO group had a higher rate. What is different from our assumption is that PS did not effectively reduce the incidence of postpartum luteal cysts. [ABSTRACT FROM AUTHOR]

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin‐dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for 'a definitive diagnosis of SPIDDM': (1) presence of anti‐islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C‐peptide immunoreactivity <0.6 ng/mL) at the last observed point in time. When a patient fulfills only (1) and (2), but not (3), he/she is diagnosed with 'SPIDDM (probable)' because the diabetes is non‐insulin‐dependent type. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the impact of subclinical ketosis (SCK) and subclinical acidosis (SCA) on dairy cow rumination, eating, drinking and locomotion behavior. It focuses on cows in their second or subsequent lactation, producing an average of 12,000 kg/year milk in their previous lactation. The cows were categorized into three groups, SCK, SCA, and healthy cows, based on the milk fat–protein ratio, blood beta-hydroxybutyrate and clinical examinations by a veterinarian. The results show significant differences between the cows affected by SCK and the healthy cows. SCK leads to a reduction in the milk yield (11.78%), rumination time (17.47%), and various eating and chewing behaviors. SCA is associated with a substantial decrease in Eating Time 2 (ET2) by 36.84% and Eating Chews 2 (EC2) by 38.10% compared to the healthy cows. These findings highlight the influence of SCA on feeding behaviors and chewing activity, with implications for nutrient intake and cow health. Additionally, SCK affects locomotion parameters, leading to a 27.36% reduction in the overall activity levels, as well as reductions in the Walking Time (WT), Other Activity Time (OAT), and Activity Change (AC). Early detection and effective management of SCK are crucial for maintaining dairy cow health and productivity. In conclusion, this research underscores the need for advanced strategies to prevent and manage subclinical metabolic disorders in the dairy industry. Effective management and early detection methods are essential to mitigate the impact of SCK and SCA on dairy cow health and benefit the dairy farming sector. This study delves into the effects of subclinical ketosis (SCK) and subclinical acidosis (SCA) on various parameters related to dairy cow rumination, eating, drinking and locomotion behavior. The research hypothesized that these subclinical metabolic disorders could affect behaviors such as rumination, feeding, and locomotion. A total of 320 dairy cows, with a focus on those in their second or subsequent lactation, producing an average of 12,000 kg/year milk in their previous lactation, were examined. These cows were classified into three groups: those with SCK, those with SCA, and healthy cows. The health status of the cows was determined based on the milk fat–protein ratio, blood beta-hydroxybutyrate, and the results of clinical examinations performed by a veterinarian. The data collected during the study included parameters from the RumiWatch sensors. The results revealed significant differences between the cows affected by SCK and the healthy cows, with reductions observed in the rumination time (17.47%) and various eating and chewing behaviors. These changes indicated that SCK had a substantial impact on the cows' behavior. In the context of SCA, the study found significant reductions in Eating Time 2 (ET2) of 36.84% when compared to the healthy cows. Additionally, Eating Chews 2 (EC2) exhibited a significant reduction in the SCA group, with an average of 312.06 units (±17.93), compared to the healthy group's average of 504.20 units (±18.87). These findings emphasize that SCA influences feeding behaviors and chewing activity, which can have implications for nutrient intake and overall cow health. The study also highlights the considerable impact of SCK on locomotion parameters, as the cows with SCK exhibited a 27.36% reduction in the walking time levels. These cows also displayed reductions in the Walking Time (WT), Other Activity Time (OAT), and Activity Change (AC). In conclusion, this research underscores the critical need for advanced strategies to prevent and manage subclinical metabolic disorders within the dairy farming industry. The study findings have far-reaching implications for enhancing the well-being and performance of dairy cattle. Effective management practices and detection methods are essential to mitigate the impact of SCK and SCA on dairy cow health and productivity, ultimately benefiting the dairy farming sector. [ABSTRACT FROM AUTHOR]

Introduction: Mycoplasma pneumoniae necrotizing pneumonia (MPNP) is an uncommon but increasingly recognized severe complication of pneumonia, and the delayed diagnosis and treatment are prone to pulmonary sequelae. The aim of this study is to explore independent risk factors for MPNP in children with lung consolidation. Methods: A retrospective observational study was conducted on 118 children with MPNP (MPNP group) and 184 children with lung consolidation of Mycoplasma pneumoniae pneumonia (MPP) (control group) admitted to Children's Hospital Affiliated to Zhengzhou University from June 2018 to August 2023. Clinical manifestations and laboratory data were analyzed and the independent risk factors for MPNP in children were analyzed by multivariate logistic regression. Results: The age of onset, hospitalization days, fever days, proportion of dyspnea, chest pain, complications, and need for fiberoptic bronchoscopic alveolar lavage (FBAL) were higher than those in the control group, and the difference was statistically significant (P < 0.05). The levels of white blood cells (WBC), platelets, neutrophil percentage (N%), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), fibrinogen (Fbg), D-dimer (D-D), erythrocyte sedimentation rate (ESR), alanine transaminase (ALT), γ-glutamyl transpeptidase (γ-GGT), globulin, lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), urea, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), complement component 3, antistreptolysin O (ASO), serum ferritin, and interleukin-6 (IL-6) in the MPNP group were higher than those in the control group. Red blood cell (RBC), lymphocyte percentage (L%), activated partial thromboplastin time (APTT), alkaline phosphatase (ALP), total protein, albumin, albumin-to-globulin ratio (AGR), creatine kinase (CK), uric acid, natrium, chlorine, calcium, and complement C4 in the MPNP group were lower than those in the control group, and the difference was statistically significant (P < 0.05). The results of multivariate logistic regression analysis showed that age ≥ 83.50 months, fever days ≥ 10.50, ALT ≥ 15.25 U/l, IgM ≥ 1.46 g/l, complement C3 ≥ 1.47 g/l, Fbg ≥ 3.93 g/l, dyspnea and needing FBAL were independent risk factors for MPNP in children. Conclusions: Age, fever days, ALT, IgM, complement C3, Fbg, dyspnea, and needing FBAL were independent risk factors for MPNP in children. For children suspected of MPNP, pediatricians should pay close attention to the above indicators, strive for early diagnosis and treatment, and improve prognosis. [ABSTRACT FROM AUTHOR]

Fasting can be divided into intermittent short-term fasting (ISTF; frequent fasts lasting <24 h) and long-term fasting (LTF; fasts lasting >24 h and up to several weeks). ISTF extends lifespan and ameliorates a wide range of diseases in animal models. ISTF and ketogenic diets (KDs) reduce oxidative stress by direct actions on the mitochondria and by inducing the expression of antioxidant enzymes. The ketone body β-hydroxybutyrate suppresses inflammation by inhibiting the nucleotide oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome. Human clinical trials demonstrated disease-modifying effects of ISTF in obesity, diabetes, and chronic inflammatory disorders. Frequent switching between ketogenic and nonketogenic states may optimize health and resilience. Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality. Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases, reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality. [ABSTRACT FROM AUTHOR]