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Clinical Autonomic Research : Official... Aug 2023Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired...
PURPOSE
Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing.
METHODS
In this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions.
RESULTS
Patients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing.
CONCLUSION
Compared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS.
TRIAL REGISTRATION INFORMATION
The study was registered at ClinicalTrials.gov (NCT03681080).
Topics: Humans; Postural Orthostatic Tachycardia Syndrome; Pilot Projects; Prospective Studies; Norepinephrine; Cognition; Heart Rate; Blood Pressure
PubMed: 37261636
DOI: 10.1007/s10286-023-00950-0 -
Orphanet Journal of Rare Diseases Jan 2024Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients...
BACKGROUND
Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance.
RESULTS
A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals.
CONCLUSIONS
IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.
Topics: Humans; Fructose Intolerance; Excipients; Lactose; Fructose; Mannitol; Sorbitol; Glucose; Sucrose; Sulfites
PubMed: 38183105
DOI: 10.1186/s13023-023-03011-x -
International Journal of Surgery Case... Jul 2024Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals....
INTRODUCTION
Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals. Brucellosis is highly prevalent in Iran, with Brucella melitensis biovar 1 being the primary causative agent. Musculoskeletal symptoms, including spondylitis, sacroiliitis, and peripheral arthritis, are common in brucellosis patients, but avascular necrosis of the hip joint is extremely rare.
CASE PRESENTATION
This case report presents a middle-aged woman from Iran with untreated brucellosis infection, who developed rapidly progressing avascular necrosis affecting both hip joints. The patient's social history did not indicate any use of tobacco or alcohol. Furthermore, there was no indication of any traumatic events affecting the patient's hip joints. The patient's family history did not reveal any rheumatologic disorders, and the patient had not been diagnosed with or reported using immune suppressant medications. Laboratory results confirmed that the patient was not diagnosed with sickle cell anemia. The patient had been intolerant to the prescribed medications, Rifampin and Doxycycline. Initially, she presented with severe bilateral hip pain, anorexia, vomiting, periodic chills and fever, myalgia, and night sweats. Pelvis X-ray confirmed bilateral hip avascular necrosis, and total hip arthroplasty was scheduled but subsequently canceled due to persistent brucellosis infection. Physical examination revealed limited hip motion, pain, and inability to bear weight. Laboratory tests indicated leukocytosis, elevated levels of CRP, and high titers on Wright and 2ME tests. Intravenous Ciprofloxacin was initiated, and further investigations were scheduled.
DISCUSSION
Osteoarticular complications are common in individuals with brucellosis. The sacroiliac joints are affected in 80 % of cases, while the spinal joints are affected in 50 %. Brucella-induced arthritis can be found in over 50 % of patients, with the lower limb joints being the most commonly affected. Failure to diagnose and treat hip arthritis caused by brucellosis promptly can lead to severe complications, including dislocation and avascular necrosis of the femoral head. Avascular necrosis is a condition where bone tissue dies due to compromised blood supply. It often remains asymptomatic initially and is usually found incidentally during radiographic imaging. Osteonecrosis of the femoral head can manifest as Legg-Calve-Perthes disease or as a complication of other medical conditions. Various factors can contribute to avascular necrosis, including hip dislocation or fracture, prolonged use of certain medications, excessive alcohol consumption, and certain medical conditions. Magnetic resonance imaging is considered the standard method for diagnosing avascular necrosis. Delay in diagnosing and treating brucellosis can result in permanent bone complications.
CONCLUSION
Brucellosis, a disease prevalent in endemic regions, should be considered as a cause of severe hip pain and other vague symptoms. Timely diagnosis and management are important, especially for high-risk patients with other health conditions and poor drug compliance, to prevent complications such as avascular necrosis.
PubMed: 38843623
DOI: 10.1016/j.ijscr.2024.109808 -
Rice (New York, N.Y.) May 2024Rice is one of the most important food crops in the world, and with the development of direct seeding methods for rice, exposure to anaerobic stress has become a major...
Identification of Key Genes and Pathways for Anaerobic Germination Tolerance in Rice Using Weighted Gene Co-Expression Network Analysis (WGCNA) in Association with Quantitative Trait Locus (QTL) Mapping.
BACKGROUND
Rice is one of the most important food crops in the world, and with the development of direct seeding methods for rice, exposure to anaerobic stress has become a major factor limiting its growth.
RESULTS
In this experiment, we tested the tolerance to anaerobic germination of rice varieties NIP and HD84, and they were used as parents to construct a DH (doubled-haploid) population. The transcriptomes of NIP (highly tolerant) and HD86 (intolerant), and their progeny HR (highly tolerant) and NHR (intolerant) were sequenced from normal and anaerobic environments. The differentially-expressed genes (DEGs) were subjected to GO (Gene ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and WGCNA analyses. QTL mapping of the DH population identified tolerance to anaerobic germination-related chromosomal segments. The transcriptome results from 24 samples were combined with the anaerobic stress QTL results for 159 DH population lines to construct a metabolic network to identify key pathways and a gene interaction network to study the key genes. Essential genes were initially subjected to rigorous functional validation, followed by a comprehensive analysis aimed at elucidating their potential utility in domestication and breeding practices, particularly focusing on the exploitation of dominant haplotypes.
CONCLUSION
The results show that pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) are the starting signals of energy metabolism for coleoptile length growth, the auxin transporter EXPA is the determining signal for coleoptile length growth. The pivotal genes Os05g0498700 and Os01g0866100 exert a negative regulatory influence on coleoptile length, ultimately enhancing tolerance to anaerobic germination in rice. Analyses of breeding potential underscore the additional value of Os05g0498700-hyp2 and Os01g0866100-hyp2, highlighting their potential utility in further improving rice through breeding programs. The results of our study will provide a theoretical basis for breeding anaerobic-tolerant rice varieties.
PubMed: 38819744
DOI: 10.1186/s12284-024-00714-y -
Current Research in Food Science 2023Gluten, a group of ethanol-soluble proteins present in the endosperm of cereals, is extensively used in the food industry due to its ability to improve dough properties....
Gluten, a group of ethanol-soluble proteins present in the endosperm of cereals, is extensively used in the food industry due to its ability to improve dough properties. However, gluten is also associated with a range of gluten-related diseases (GRDs), such as wheat allergies, celiac disease, and gluten intolerance. The recommended treatment for GRDs patients is a gluten-free diet. To monitor adherence to this diet, it is necessary to develop gluten-detection systems in food products. Among the available methods, immunodetection systems are the most popular due to their simplicity, reproducibility, and accuracy. The aim of this study was to generate novel high-affinity antibodies against gluten to be used as the primary reactant in an enzyme-linked immunosorbent assay (ELISA) test. These antibodies were developed by constructing an immune library from mRNA obtained from two celiac patients with a high humoral response to gluten-related proteins. The resulting library (composed by 1.1x10) was subjected to selection against gliadin using phage display technology. Following several rounds of selection, the Fab-C was selected, and demonstrated good functionality in ELISA tests, presenting a limit of detection of 15 mg/kg for detection of gluten in spiked mixtures and food products. The methodology can discriminate gluten-free products according to the current legislation.
PubMed: 37680694
DOI: 10.1016/j.crfs.2023.100578 -
PloS One 2024The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US... (Observational Study)
Observational Study
Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study.
The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.
Topics: Humans; Adrenergic beta-Antagonists; Carvedilol; Heart Failure; Japan; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 38452137
DOI: 10.1371/journal.pone.0299510 -
Hepatology Communications Feb 2024Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS)...
BACKGROUND
Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation.
METHODS
This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated.
RESULTS
13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.217.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20-25) to 15 (13-21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= -0.9943, p<0.0001) but not before GMA (p=0.62).
CONCLUSIONS
Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words).
Topics: Humans; Pilot Projects; Monocytes; End Stage Liver Disease; Prospective Studies; Severity of Illness Index; Blood Component Removal; Granulocytes; Hepatitis, Alcoholic; Adrenal Cortex Hormones; Steroids; Macrophages
PubMed: 38285891
DOI: 10.1097/HC9.0000000000000371 -
Journal of Materials Science. Materials... Jan 2024Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor....
Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment.
Topics: Humans; Cadmium Compounds; Multiple Myeloma; Tellurium; Hematopoietic Stem Cell Transplantation; Quantum Dots; Transplantation, Autologous; Doxorubicin; Drug Carriers; Polyethylene Glycols; Cell Line, Tumor; Drug Delivery Systems; Tumor Microenvironment; Receptors, CXCR4
PubMed: 38244066
DOI: 10.1007/s10856-023-06772-w -
Nutrients Apr 2024Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether...
Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.
Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha () and low-density lipoprotein receptor (), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.
Topics: Animals; Female; Pregnancy; Choline; Ethanol; Male; Dietary Supplements; Liver; Prenatal Exposure Delayed Effects; Mice, Inbred C57BL; Mice; Fatty Liver; Triglycerides; PPAR alpha; Receptors, LDL; Glucose Intolerance; Lipid Metabolism
PubMed: 38732511
DOI: 10.3390/nu16091264