Medical management for the prevention of kidney stones

The alarming fact is that approximately one out of every 10 of us will have a kidney stone during our lifetime. The increasing prevalence and associated costs of kidney stones have resulted in it being one of the most commonly encountered and impactful medical conditions. Contributing factors include, but are not limited to, diet, climate, genetics, medications, activity and underlying medical conditions. Symptoms generally parallel stone size. Treatment varies from supportive to procedural (invasive and non-invasive). Prevention remains the best way to avoid this condition especially given the high recurrence rate. First time stone formers require counselling regarding dietary adjustments. Certain risk factors ultimately require a more in-depth metabolic investigation, especially if stones are recurrent. Ultimately, management is defined by stone composition. Where appropriate, we review both pharmacologic and non-pharmacologic options. Pivotal to successful prevention is patient education and the encouragement of compliance with the appropriate regimen.

Genome-centric metagenomics reveals insights into the evolution and metabolism of a new free-living group in Rhizobiales

Background The Rhizobiales (Proteobacteria) order is an abundant and diverse group of microorganisms, being extensively studied for its lifestyle based on the association with plants, animals, and humans. New studies have demonstrated that the last common ancestor (LCA) of Rhizobiales had a free-living lifestyle, but the phylogenetic and metabolism characterization of basal lineages remains unclear. Here, we used a high-resolution phylogenomic approach to test the monophyly of the Aestuariivirgaceae family, a new taxonomic group of Rhizobiales. Furthermore, a deep metabolic investigation provided an overview of the main functional traits that can be associated with its lifestyle. We hypothesized that the presence of pathways (e.g., Glycolysis/Gluconeogenesis) and the absence of pathogenic genes would be associated with a free-living lifestyle in Aestuariivirgaceae. Results Using high-resolution phylogenomics approaches, our results revealed a clear separation of Aestuariivirgaceae into a distinct clade of other Rhizobiales family, suggesting a basal split early group and corroborate the monophyly of this group. A deep functional annotation indicated a metabolic versatility, which includes putative genes related to sugar degradation and aerobic respiration. Furthermore, many of these traits could reflect a basal metabolism and adaptations of Rhizobiales, as such the presence of Glycolysis/Gluconeogenesis pathway and the absence of pathogenicity genes, suggesting a free-living lifestyle in the Aestuariivirgaceae members. Conclusions Aestuariivirgaceae (Rhizobiales) family is a monophyletic taxon of the Rhizobiales with a free-living lifestyle and a versatile metabolism that allows these microorganisms to survive in the most diverse microbiomes, demonstrating their adaptability to living in systems with different conditions, such as extremely cold environments to tropical rivers.

Novel GLDC Compound Heterozygous Variant Leading to Nonketotic Hyperglycinemia: Case Report and Literature Review

Nonketotic hyperglycinemia (NKH) is a lethal autosomal recessive disease resulting from alterations in glycine metabolism, commonly caused by mutations in glycine decarboxylase (GLDC). The symptoms of NKH usually manifest in the neonatal period, and can be categorized into severe NKH and attenuated NKH based on the clinical outcome. To date, only a few NKH cases have been reported in China. We here report a case of a neonate with severe NKH carrying a novel compound heterozygous variant in GLDC. The patient was a 68-h-old girl who had progressive lethargy, no crying, and poor sucking ability from birth, and was therefore transferred to our department. On admission, the patient was supported by intubation and ventilation and presented with profound coma. Metabolic investigation indicated a markedly increased glycine concentration both in the plasma and cerebrospinal fluid (CSF). Symptomatic treatments were administered, but the patient's condition did not improve substantially. Whole-exome sequencing identified compound heterozygous mutations (c.1261G>C, p.G421R and c.450 C>G, p.N150K) in GLDC, which were inherited from the mother and the father, respectively. The patient was hospitalized for 8 days in our department and died 2 days after discharge. We further summarize the clinical features, genetic characteristics, administered treatment, and prognosis of previously reported Chinese NKH patients for context. Our results highlight that due to the non-specific clinical phenotypes of NKH and difficulty in obtaining CSF samples, genetic testing is a crucial tool, not only for a diagnosis but also for predicting the clinical outcome and can potentially help to determine the optimal therapeutic strategy.

Seasonal Metabolic Investigation in Pomegranate (Punica granatum L.) Highlights the Role of Amino Acids in Genotype- and Organ-Specific Adaptive Responses to Freezing Stress

Every winter, temperate woody plants have to cope with freezing stress. Winter hardiness is of crucial importance for pomegranate survival and productivity. A comparative morphological and metabolic study was conducted on the stems and buds of 15 field-grown mature pomegranate genotypes in seven time-points during two developmental cycles. Seasonal changes of frost hardiness, as determined by electrolyte leakage method, and metabolite analysis by HPLC and GC revealed the variability in frost hardiness and metabolic contents result from genetic background and organ, as well as seasonal condition. Morphological adaptations, as well as metabolic remodeling, are the distinct features of the hardy genotypes. Larger buds with a greater number of compressed scales and the higher number of protective leaves, together with the higher number and content of changed metabolites, especially amino acids, seem to provide a higher frost resistance for those trees. We recorded two-times the change in metabolites and several-times accumulation of amino acids in the stem compared with buds. A better potential of stem for metabolome adjustment during the hardening period and a higher level of tolerance to stress is therefore suggested. High levels of arginine, proline, glutamine, and asparagine, and particularly the accumulation of alanine, tryptophan, and histidine are responsible for excellent tolerance of the stem of tolerant genotypes. With regard to the protective roles of amino acids, a relation between stress tolerance and the level of amino acids is proposed. This points both to the importance of amino acids in the winter survival of pomegranate trees, and to the evaluation of frost tolerance in other plants, by these specific markers.

Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile

The virulence of Clostridioides difficile (formerly Clostridium difficile) is mainly caused by its two toxins A and B. Their formation is significantly regulated by metabolic processes. Here we investigated the influence of various sugars (glucose, fructose, mannose, trehalose), sugar derivatives (mannitol and xylitol) and L-lactate on toxin synthesis. Fructose, mannose, trehalose, mannitol and xylitol in the growth medium resulted in an up to 2.2-fold increase of secreted toxin. Low glucose concentration of 2 g/L increased the toxin concentration 1.4-fold compared to growth without glucose, while high glucose concentrations in the growth medium (5 and 10 g/L) led to up to 6.6-fold decrease in toxin formation. Transcriptomic and metabolic investigation of the low glucose effect pointed towards an inactive CcpA and Rex regulatory system. L-lactate (500 mg/L) significantly reduced extracellular toxin formation. Transcriptome analyses of the later process revealed the induction of the lactose utilization operon encoding lactate racemase (larA), electron confurcating lactate dehydrogenase (CDIF630erm_01321) and the corresponding electron transfer flavoprotein (etfAB). Metabolome analyses revealed L-lactate consumption and the formation of pyruvate. The involved electron confurcation process might be responsible for the also observed reduction of the NAD+/NADH ratio which in turn is apparently linked to reduced toxin release from the cell.

MUCOPOLYSACARIDOSIS TYPE IIIB MISDIAGNOSED AS AN AUTISTIC SPECTRUM DISORDER: A CASE REPORT AND LITERATURE REVIEW

ABSTRACT Objective: To report a rare case of mucopolysaccharidosis IIIB in a pediatric patient, with emphasis on the description of the clinical manifestations and the early diagnosis. Case description: A 14-year-old male patient, who presented regression of neuropsychomotor development since his three years and six months old, with speech loss and frequent falls, evolving with behavioral changes, with agitation and aggressiveness. Although being diagnosed with autism, there was no response to the established treatment; he was subsequently submitted to metabolic investigation, which lead to the diagnosis of Mucopolysaccharidosis IIIB. Comments: Identifying a metabolic disorder requires connecting multiple signs and symptoms, as well as eliminating other apparent causes. MPS IIIB is a diagnostic challenge, particularly in the early stages and in the absence of a family history of the disease.

Cases of inborn errors of metabolism diagnosed in children with autism

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

Cytological-energy analysis of pleural effusions

Background Simultaneous cytological and metabolic investigation of the pleural effusion provides clinically relevant information about the type and intensity of immune response in the pleural cavity. Methods We investigated 1329 pleural effusions from patients with different pathological changes in the pleural cavity. Evaluated parameters were differential cell count of neutrophils, eosinophils, lymphocytes and monocytes, and values of the coefficient of energy balance. Results We found the lowest numbers of cells and the highest coefficient of energy balance values in patients with heart failure and sepsis; relatively high frequency of eosinophils and slightly decreased coefficient of energy balance values in patients with pneumothorax and haemothorax; the predominance of lymphocytes and low coefficient of energy balance values in patients with tuberculous pleuritis; the predominance of neutrophils and variable coefficient of energy balance values in patients after chest surgery; the highest presence of neutrophils and very low coefficient of energy balance values in patients with chest empyema and the predominance of lymphocytes and normal to low coefficient of energy balance values in patients with pleural malignancy. Conclusions Our findings in patients with heart failure and sepsis suggest the absence of inflammation in the pleural cavity. We observed the manifestation of tissue repair in patients with pneumothorax and haemothorax. Patients with tuberculous pleuritis were predominantly characterized by T cell-driven immune response and oxidative burst of macrophages. We found different intensities of immune responses to the chest surgery. The typical finding in patients with empyema was oxidative burst of neutrophils. In patients with pleural malignancy, weak cytotoxic inflammation predominates together with the intensive inflammation characterized by oxidative burst of macrophages.