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Journal of Dairy Science Jun 2024Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery...
Changes in Rumen Epithelial Morphology and Transcriptome, Rumen Metabolome, and Blood Biochemical Parameters in Lactating Dairy Cows with Subacute Rumen Acidosis Following Rumen Content Transplantation.
Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of subacute ruminal acidosis (SARA) remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum/basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEGs) were identified between the 2 groups. Enrichment analysis showed that the DEGs were significantly enriched in 11 Gene Ontology biological processes and 14 KEGG pathways. The DEGs corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino sugar and nucleotide metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino sugar and nucleotide sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.
PubMed: 38908691
DOI: 10.3168/jds.2024-24694 -
Medicina 2024Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also...
Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.
Topics: Humans; Acetaminophen; Female; Adult; Liver Transplantation; Liver Failure, Acute; Suicide, Attempted; Analgesics, Non-Narcotic; Drug Overdose
PubMed: 38907980
DOI: No ID Found -
Diabetologia Jun 2024The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American...
The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE) and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycaemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment and prevention of diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes healthcare professionals and individuals with diabetes.
PubMed: 38907161
DOI: 10.1007/s00125-024-06183-8 -
ACS Nano Jun 2024This study investigates transfer ribonucleic acid (tRNA) conformational dynamics in the context of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and...
This study investigates transfer ribonucleic acid (tRNA) conformational dynamics in the context of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) using solid-state silicon nitride (SiN) nanopore technology. SiN nanopores in thin membranes with specific dimensions exhibit high signal resolution, enabling real-time and single-molecule electronic detection of tRNA conformational changes. We focus on human mitochondrial tRNALeu(UAA) (mt-Leu(UAA)) that decodes Leu codons UUA/UUG (UUR) during protein synthesis on the mt-ribosome. The single A14G substitution in mt-Leu(UAA) is the major cause of MELAS disease. Measurements of current blockades and dwell times reveal distinct conformational dynamics of the wild-type (WT) and the A14G variant of mt-Leu(UAA) in response to the conserved post-transcriptional mG9 methylation. While the mG9-modified WT transcript adopts a more stable structure relative to the unmodified transcript, the mG9-modified MELAS transcript adopts a less stable structure relative to the unmodified transcript. Notably, these differential features were observed at 0.4 M KCl, but not at 3 M KCl, highlighting the importance of experimental settings that are closer to physiological conditions. This work demonstrates the feasibility of the nanopore platform to discern tRNA molecules that differ by a single-nucleotide substitution or by a single methylation event, providing an important step forward to explore changes in the conformational dynamics of other RNA molecules in human diseases.
PubMed: 38906834
DOI: 10.1021/acsnano.4c04625 -
Frontiers in Pediatrics 2024Type 1 diabetes mellitus (T1DM) is a metabolic disorder characterized by an absolute deficiency of insulin due to pancreatic failure. Diabetes ketoacidosis (DKA) has...
Type 1 diabetes mellitus (T1DM) is a metabolic disorder characterized by an absolute deficiency of insulin due to pancreatic failure. Diabetes ketoacidosis (DKA) has emerged as one of the most common complications of T1DM. Although exceedingly rare, the onset of T1DM with DKA may result in lipemia secondary to severe hypertriglyceridemia (HTG), accounting for several cases in the pediatric population. Along this line, plasma exchange treatment in children with DKA and severe hyperlipidemia has only been reported in some cases. In this case report, the diagnosis of an 11-year-old girl with diabetes ketoacidosis accompanied by severe HTG, along with subsequent plasma exchange treatment, is presented. Initially, the patient received initial management with crystalloid fluid bolus and intravenous insulin therapy. Despite rapid correction of acidosis, persistent HTG subsequently prompted the plasma exchange treatment. A total of three sessions were administered over 2 days, leading to a significant reduction in the triglyceride levels and corneal opacity resolution, indicating a successful therapeutic intervention.
PubMed: 38903770
DOI: 10.3389/fped.2024.1280330 -
Cureus May 2024In patients with diabetes, diabetic ketoacidosis (DKA) is a well-documented potential complication, usually presenting with hyperglycemia, anion gap acidosis, and...
In patients with diabetes, diabetic ketoacidosis (DKA) is a well-documented potential complication, usually presenting with hyperglycemia, anion gap acidosis, and positive ketones. Metformin toxicity in the setting of acute renal failure is also a well-known cause of lactic acidosis. However, metformin-induced euglycemic ketoacidosis is less well-known or studied. We report a case of metformin toxicity in the setting of acute renal failure with both lactic acidosis and ketosis and an initial confounded clinical presentation of sulphonylurea-induced hypoglycemia. A high index of suspicion for metformin-associated lactic acidosis (MALA) and metformin-associated lactic acidosis with euglycemic ketoacidosis (MALKA) should be in place in patients who are taking metformin and presenting with acute renal failure and euglycemia.
PubMed: 38899266
DOI: 10.7759/cureus.60661 -
Kidney International Reports Jun 2024We investigated the relationship between metabolic acidosis over time and allograft outcome in pediatric kidney transplantation (KTx).
INTRODUCTION
We investigated the relationship between metabolic acidosis over time and allograft outcome in pediatric kidney transplantation (KTx).
METHODS
This registry study collected data up to 10 years posttransplant. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤ 30 ml/min per 1.73 m or ≥50% decline from eGFR at month 3 posttransplant was performed. The association of serum bicarbonate concentration (HCO ) < 22 mmol/l (metabolic acidosis) and HCO < 18 mmol/l (severe metabolic acidosis) with allograft outcome was investigated using stratified Cox models and marginal structural models. Secondary analyses included the identification of risk factors for metabolic acidosis and the relationship between alkali supplementation and allograft outcome.
RESULTS
We report on 1911 patients, of whom 347 reached the composite end point. The prevalence of metabolic acidosis over time ranged from 20.4% to 38.9%. In the adjusted Cox models, metabolic acidosis (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.54-2.60) and severe metabolic acidosis (HR, 2.49; 95% CI, 1.56-3.99) were associated with allograft dysfunction. Marginal structural models showed similar results (HR, 1.75; 95% CI, 1.32-2.31 and HR, 2.09; 95% CI, 1.23-3.55, respectively). Older age was associated with a lower risk of metabolic acidosis (odds ratio [OR] 0.93/yr older; 95% CI, 0.91-0.96) and severe metabolic acidosis (OR, 0.89; 95% CI, 0.84-0.95). Patients with uncontrolled metabolic acidosis had the worst outcome compared to those without metabolic acidosis and without alkali (HR, 3.70; 95% CI, 2.54-5.40).
CONCLUSION
The degree of metabolic acidosis is associated with allograft dysfunction.
PubMed: 38899185
DOI: 10.1016/j.ekir.2024.04.007 -
Pediatrics International : Official... 2024
Topics: Humans; Bradycardia; Female; Mitochondrial Diseases; Pregnancy; Infant, Newborn; Fetal Diseases; Adult; Ultrasonography, Prenatal; Male
PubMed: 38898703
DOI: 10.1111/ped.15771 -
The American Journal of Case Reports Jun 2024BACKGROUND Diabetes mellitus is a chronic disease that occurs when the pancreas does not produce enough insulin or when the body is unable to effectively use the insulin...
BACKGROUND Diabetes mellitus is a chronic disease that occurs when the pancreas does not produce enough insulin or when the body is unable to effectively use the insulin it produces. Uncontrolled diabetes mellitus is usually associated with neurological manifestations, such as hemichorea, focal epileptic seizures, peripheral neuropathy, and peripheral facial paralysis. This report describes a 59-year-old woman presenting with hyperglycemia and ketoacidosis due to newly diagnosed diabetes mellitus, as well as a temporary episode of central facial paralysis, which regressed within a few days after medical treatment and metabolic correction. CASE REPORT A 59-year-old patient with hypertension and a family history of diabetes mellitus presented with polyuro-polydipsic syndrome and signs of metabolic ketoacidosis, with an elevated anion gap, compatible with newly discovered type 1 diabetes mellitus. Six hours after admission, we noted the abrupt onset of left central facial paralysis, with no brain damage shown on magnetic resonance imaging. Initially, the diagnosis was transient ischemic attack. After a second, normal cerebral magnetic resonance image on the fourth day, and clinical improvement on the fifth day after metabolic correction by insulin therapy and rehydration, the diagnosis of a regressive central facial paralysis was retained. CONCLUSIONS Central facial paralysis in diabetic ketoacidosis is a rare neuroendocrine entity. The pathophysiological mechanisms that can explain the occurrence of central facial paralysis are not yet described and require further investigation. This report highlights the importance of diagnosis, early management of hyperglycemia and diabetic ketoacidosis, and reversibility of central facial paralysis after treatment.
Topics: Humans; Female; Middle Aged; Facial Paralysis; Diabetic Ketoacidosis; Hyperglycemia; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Insulin
PubMed: 38898638
DOI: 10.12659/AJCR.942425 -
Arquivos Brasileiros de Cirurgia... 2024Lower urinary tract abnormalities are directly implicated in the etiology of renal dysfunction in 6 to 24% of dialytic patients. These patients require bladder capacity... (Review)
Review
Lower urinary tract abnormalities are directly implicated in the etiology of renal dysfunction in 6 to 24% of dialytic patients. These patients require bladder capacity and compliance readjustment before being considered viable candidates for renal transplantation. Vesical augmentation surgeries often involve the use of intestinal segments. Although these procedures can effectively restore bladder capacity and compliance, they present various issues related to maintaining mucous absorption and secretion capacity. Acidosis, recurrent urinary tract infections, and stone formation are extremely common, leading to frequent hospitalizations and graft function loss. Urinary tissue is certainly ideal for these reconstructions; however, bladder augmentation using ureter and renal pelvis are feasible only in a minority of cases. Experimental studies have been conducted to establish the groundwork for vascularized bladder transplantation. Last year, for the first time, this procedure was performed on a brain-dead patient. During this intervention, cystectomy was performed with preservation the vascular pedicle, followed by organ reimplantation. The graft remained viable for a period of 12 hours post-transplant. However, this intervention utilized a robotic platform, making it less reproducible in a multi-organ procurement setting as well as for most transplant centers. Moreover, it is debatable whether the benefits of exclusive bladder transplantation outweigh the risks associated with immunosuppression. For patients needing renal transplantation and requiring lower urinary tract reconstruction, however, utilizing the donor's bladder may offer an attractive alternative, avoiding the inherent complications of enterocystoplasty without increasing immunological risk. Combined kidney and bladder transplantation has the potential to emerge as the next frontier in abdominal organ transplants.
Topics: Humans; Urinary Bladder; Kidney Transplantation; Organ Transplantation
PubMed: 38896703
DOI: 10.1590/0102-6720202400015e1808