Acute diarrhea in the hospitalized immunocompromised patient: what is new on diagnostic and treatment?

PURPOSE OF THIS REVIEW: This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS: Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY: Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.

Rapid discrimination of geographical origin of garlic (Allium sativum L.): A metabolomic approach applied to paper spray mass spectrometry data.

INTRODUCTION: Distinguishing and categorizing the origin of garlic are highly significant, considering its widespread use as a flavoring agent. With billions of dollars annually in global trade, garlic is frequently susceptible to fraudulent practices. METHODOLOGY: Paper spray ionization mass spectrometry (PS-MS) was employed to quickly analyze garlic samples from distinct geographic origins: China and Brazil. The so-generated PS-MS data were treated with metabolomic multivariate approaches, and the garlic samples from these different geographic regions were easily discriminated. RESULTS: Brazilian garlic was characterized to contain higher levels of amino acids, such as arginine, proline, and valine, and organosulfur compounds, such as allicin, alliin, and l-γ-glutamil-S-allyl-l-cysteine, compared to Chinese garlic. The PS-MS data were treated employing multivariate approaches, typically used in the metabolomics field, and this protocol was promptly able to discern among both types of samples. CONCLUSION: Hence, this combined strategy holds promise not only as an effective tool for the authentication of the geographical origin of garlic but also as a powerful means for biomarker discovery.

Reconsidering the role of nasolabial angle in premolar extraction decision-making: A case-series study.

OBJECTIVES: To evaluate the impact of changes in upper incisor inclination and position on the alteration of the nasolabial angle (NLA) in a series of cases involving the extraction of four first premolars. MATERIALS AND METHODS: The study included 41 patients who underwent orthodontic treatment with premolar extractions. The patients were divided into two groups based on their pretreatment NLA values: Group 1 (NLA ≤ 100°) and Group 2 (NLA > 100°). Measurements of NLA, U1.NA and U1-NA were obtained before and after treatment and U1-Ls pretreatment measure was registered. Statistical analyses were performed to compare the differences in NLA, U1.NA and U1-NA between the two groups and to evaluate the influence of these variables added to U1-Ls (T1) on NLA changes. RESULTS: The results showed that Group 1 exhibited significant changes in NLA, while Group 2 did not. However, both groups showed significant changes in U1.NA and U1-NA. In Group 1, 80% of the individuals presented an increase in NLA and 20% no changes. In Group 2, 10% presented a decrease, 57% no changes and 33% an increase in NLA values. Multiple linear regression analysis indicated that the group factor had a statistically significant influence on NLA variation. Additionally, in Group 2, a negative correlation was observed between changes in U1.NA and NLA. CONCLUSIONS: The findings suggest that individuals with higher pretreatment NLA values tend to maintain their NLA values even after the correction of upper incisor inclination.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Eye movement impairments in children with malnutrition.

Malnutrition is characterised by deficient nutrient ingestion and absorption and is still one of the most important causes of morbidity and mortality in children worldwide. Our main rationale was that protein-energy malnutrition (PEM) may affect eye movement in children with malnutrition. Twenty children without PEM (mean age = 10.8; SD = 1.0 years) and 18 children with PEM (mean age = 10.9; SD = 1.2 years) were included in the present study. We applied three types of tests: one that consisted of a maze and two versions of the Spot the Seven Errors test using boats and elephants. Our results indicated that children with PEM exhibited performance deficits in the maze test (p < .001) and Spot the Seven Errors test for both boats (p < .001) and elephants (p < .001). These data suggest that nutritional impairments during the first year of life (i.e., a critical period) can directly impact eye movement. Eye tracking is a reliable technique to investigate higher-order processes, but our results should be interpreted with caution. Our findings highlight the relevance of cognitive development in malnourished children, which can negatively affect their development. Screening, assessment and rehabilitation strategies are essential in this at-risk population.

Current and Emerging Treatments for Waldenström Macroglobulinemia.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma. The primary goal of therapy is to reduce symptoms related to direct infiltration of the bone marrow and decrease monoclonal IgM-associated complications. Active agents in the management of WM can be broadly classified as rituximab-alkylator combination therapy, proteasome inhibitor-based therapy, and Bruton's tyrosine kinase inhibitor-based therapy. MYD88L265P and CXCR4 genetic status are pivotal for tailoring treatment options. Ibrutinib is a suitable treatment option for both treatment-naïve and relapsing WM patients. Recent advances in the intracellular B cell and cytokine signaling pathways have contributed to the development of novel therapeutic strategies. Current clinical trials are promising and may further advance WM-directed therapy.

Pain scores at the insertion of the 52 MG levonorgestrel-releasing intrauterine system among nulligravidas and parous women.

PURPOSE: This study aimed to assess the pain scores at the insertion of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) among nulligravidas, parous women with previous vaginal delivery and parous women with elective caesarean-delivery without any previous labour or cervix dilation. MATERIALS AND METHODS: The present research is a prospective, single-cohort study that included 413 women aged 15-49 years who opted for LNG-IUS placement for contraception or treatment of heavy menstrual bleeding. Women who participated in the present study were not submitted to any pharmacological pain-relieving intervention to perform the procedure. Pain at insertion was evaluated by using a Visual Analogue Scale (VAS). Pain was classified as absent (0), mild (1-3), moderate (4-6), or severe (7-10). The women were divided as: (1) nulligravidas, (2) parous women with a previous vaginal delivery, or (3) parous women with elective caesarean-delivery without any previous labour or cervix dilation. RESULTS: Nulligravidas women presented a higher mean pain score, when compared to women with elective caesarean-delivery and women with previous vaginal delivery (6.6 ± 2.0 vs 5.5 ± 2.1 and 3.9 ± 2.4, respectively; p < 0.001). Nulligravidas and women with elective caesarean-delivery were more likely to have pain classified as moderate or severe (in relation to absent or mild) than women with previous vaginal delivery (p < 0.001). Multiple Linear Regression Analysis demonstrated that 29.5% of all variability of the pain score was explained by two predictor/independent variables: nulligravidas or women with elective caesarean and difficulty at IUD insertion. CONCLUSIONS: Women with previous vaginal delivery had lower pain scores at LNG-IUS insertion when compared to nulligravidas and women with elective caesarean-delivery without any previous labour.

Quantitative Proteome Analysis of Jatropha curcas L. Genotypes with Contrasting Levels of Phorbol Esters.

The phorbol esters in the seeds of Jatropha curcas are a major hindrance to the full exploitation of the potential of this oil crop as a source of raw material for the production of biodiesel. Here, various quantitative proteomic strategies are used to establish the proteomes of roots, leaves, and endosperm of two genotypes of J. curcas with contrasting levels of phorbol esters in the seeds. In total 4532, 1775, and 503 proteins are identified respectively in roots, leaves, and endosperm, comprising 5068 unique proteins; of this total, 185 are differentially abundant in roots, 72 in leaves, and 20 in the endosperm. The biosynthetic pathways for flavonoids and terpenoids are well represented in roots, including the complete set of proteins for the mevalonate and non-mevalonate/Deoxyxylulose 5-Phosphate pathways, and proteins involved in the branches which lead to the synthesis tricyclic diterpenoids and gibberellins. Also, casbene synthase which catalyzes the first committed step in the biosynthesis of tigliane-type diterpenes is identified in roots of both genotypes, but not in leaves and endosperm. This dataset will be a valuable resource to explore the biochemical basis of the low toxicity of Jatropha genotypes with low concentration of phorbol esters in the seeds.

1 H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae.

NSD3s, the proline-tryptophan-tryptophan-proline (PWWP) domain-containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using 1 H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein-dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming.

Mice chronically fed a high-fat diet are resistant to malaria induced by Plasmodium berghei ANKA.

C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) develop neurological symptoms and die 6--7-day post-inoculation in the absence of high parasitemia. The effects of chronic intake of a high-fat diet on this process are largely unknown. In this study, we assessed the effect of a high-fat diet on the host-parasite response to malarial infection. Mice were fed ad libitum with either standard or a high-fat diet for 8 weeks and afterwards were infected with PbA. PbA-infected mice feeding a standard diet presented blood parasitemia, hepatic and cerebral histopathological alterations, and hepatic injury with increased hemozoin deposition in the liver. By contrast, these changes were not observed in the malaria high-fat diet group. In addition, mice fed a high-fat diet did not develop the expected neurological symptoms of cerebral malaria and were resistant to death. Taken together, our results indicate that chronic ingestion of high-fat diet prevents the development of experimental malaria induced by PbA injection, suggesting a relationship between a high-fat diet and malaria, which is an interesting subject for further study in humans.

1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose Binds to the N-terminal Metal Binding Region to Inhibit Amyloid ß-protein Oligomer and Fibril Formation.

The early oligomerization of amyloid ß-protein (Aß) is a crucial step in the etiology of Alzheimer's disease (AD), in which soluble and highly neurotoxic oligomers are produced and accumulated inside neurons. In search of therapeutic solutions for AD treatment and prevention, potent inhibitors that remodel Aß assembly and prevent neurotoxic oligomer formation offer a promising approach. In particular, several polyphenolic compounds have shown anti-aggregation properties and good efficacy on inhibiting oligomeric amyloid formation. 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose is a large polyphenol that has been shown to be effective at inhibiting aggregation of full-length Aß1-40 and Aß1-42, but has the opposite effect on the C-terminal fragment Aß25-35. Here, we use a combination of ion mobility coupled to mass spectrometry (IMS-MS), transmission electron microscopy (TEM) and molecular dynamics (MD) simulations to elucidate the inhibitory effect of PGG on aggregation of full-length Aß1-40 and Aß1-42. We show that PGG interacts strongly with these two peptides, especially in their N-terminal metal binding regions, and suppresses the formation of Aß1-40 tetramer and Aß1-42 dodecamer. By exploring multiple facets of polyphenol-amyloid interactions, we provide a molecular basis for the opposing effects of PGG on full-length Aß and its C-terminal fragments.

Amino Acid Metaclusters: Implications of Growth Trends on Peptide Self-Assembly and Structure.

Ion-mobility mass spectrometry is utilized to examine the metacluster formation of serine, asparagine, isoleucine, and tryptophan. These amino acids are representative of different classes of noncharged amino acids. We show that they can form relatively large metaclusters in solution that are difficult or impossible to observe by traditional solution techniques. We further demonstrate, as an example, that the formation of Ser metaclusters is not an ESI artifact because large metaclusters can be detected in negative polarity and low concentration with similar cross sections to those measured in positive polarity and higher concentration. The growth trends of tryptophan and isoleucine metaclusters, along with serine, asparagine, and the previously studied phenylalanine, are balanced among various intrinsic properties of individual amino acids (e.g., hydrophobicity, size, and shape). The metacluster cross sections of hydrophilic residues (Ser, Asn, Trp) tend to stay on or fall below the isotropic model trend lines whereas those of hydrophobic amino acids (Ile, Phe) deviate positively from the isotropic trend lines. The growth trends correlate well to the predicted aggregation propensity of individual amino acids. From the metacluster data, we introduce a novel approach to score and predict aggregation propensity of peptides, which can offer a significant improvement over the existing methods in terms of accuracy. Using a set of hexapeptides, we show that the strong negative deviations of Ser metaclusters from the isotropic model leads a prediction of microcrystalline formation for the SFSFSF peptide, whereas the strong positive deviation of Ile leads to prediction or fibril formation for the NININI peptide. Both predictions are confirmed experimentally using ion mobility and TEM measurements. The peptide SISISI is predicted to only weakly aggregate, a prediction confirmed by TEM.

Prosthetic replacement vs space closure for maxillary lateral incisor agenesis: A systematic review.

INTRODUCTION: Defining the best treatment for maxillary lateral incisor agenesis is a challenge. Our aim in this study was to determine, with the evidence available in the literature, the best treatment for maxillary lateral incisor agenesis in the permanent dentition, evaluating the esthetic, occlusal (functional), and periodontal results between prosthetic replacement and orthodontic space closure. METHODS: Electronic databases (CENTRAL, PubMed, Web of Science, Scopus, and LILACS) were searched in September 2014 and updated in January 2015, with no restriction on language or initial date. A manual search of the reference lists of the potential studies was performed. Risk of bias was assessed by the Newcastle Ottawa Scale. RESULTS: The search identified 2174 articles, of which 1196 were excluded because they were duplicates. Titles and abstracts of 978 articles were accessed, and 957 were excluded. In total, 21 articles were read in full, and 9 case-control studies were included after applying the inclusion and exclusion criteria. Data were extracted from the articles selected, and a table was compiled for comparison and analysis of the results. There were no randomization and blinding, and the risk of bias evaluation found gaps in compatibility and outcome domains in almost all selected studies. CONCLUSIONS: Tooth-supported dental prostheses of maxillary lateral incisor agenesis had worse scores in the periodontal indexes than did orthodontic space closure. Space closure is evaluated better esthetically than prosthetic replacements, and the presence or absence of a Class I relationship of the canines showed no relationship with occlusal function or with signs and symptoms of temporomandibular disorders.

Determination of the volatile chemical profile of Momordica charantia (bitter melon) leaf and fruit by GC-MS.

The plant Momordica charantia (Cucurbitaceae), popularly known as bitter melon, snake fruit, Saint Vincent's herb, or little melon, is an African species that has developed in tropical and subtropical biomes in various parts of Brazil. The fruit is used in various traditional medicinal applications. The study aimed to identify the compounds of the essential oil of the leaves obtained by hydrodistillation and in the fruit through Solid-Phase Microextraction by headspace mode (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). The analysis of mature fruits led to the identification of 18 compounds, compared to the hydrodistillation, in which 21 compounds were identified. Benzaldehyde, linalool, and ß-cyclocitral were identified in both methods. Linalool was the major compound in both processes. These findings highlight the importance of knowing the chemical composition of organic volatile compounds (VOCs), given the potential for medicinal applications and popular use of plants.