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Cell Feb 2024Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although...
Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.
Topics: Animals; Mice; Anti-Bacterial Agents; Butyrates; Carbohydrate Metabolism, Inborn Errors; Clostridium; Escherichia coli; Gastrointestinal Microbiome; Sorbitol
PubMed: 38366592
DOI: 10.1016/j.cell.2024.01.029 -
Revue Medicale de Liege Feb 2024The COVID-19 pandemic has had a deleterious impact on students. Studies showed an increase in anxiety-depressive symptoms and changes in certain health behaviours...
The COVID-19 pandemic has had a deleterious impact on students. Studies showed an increase in anxiety-depressive symptoms and changes in certain health behaviours (smoking, drugs, etc.). The aim of the present study is to measure whether students' alcohol consumption changed during the third confinement (frequency and quantity) in relation to the factor of intolerance to uncertainty. The study was conducted on a sample of 273 French-speaking Belgian students (Universities and High Schools). The students answered questionnaires measuring their psycho-emotional state, alcohol consumption and intolerance of uncertainty and its mechanisms. Results showed that 65 % of the students had anxiety symptoms. Alcohol consumption remained moderate, with 85 % having not changed the frequency of consumption and 89 % their quantity of alcohol. Finally, the results indicated that the increase in alcohol consumption was essentially linked to positive expectations about the effects of alcohol, but not to measures of anxiety or intolerance of uncertainty. The study highlights the need for national prevention strategies to detect psychological distress in post-pandemic students.
Topics: Humans; COVID-19; Pandemics; Uncertainty; Belgium; Alcohol Drinking; Psychological Distress; Students; Depression
PubMed: 38356422
DOI: No ID Found -
Cureus Dec 2023Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient....
Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity. Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.
PubMed: 38288178
DOI: 10.7759/cureus.51286 -
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 -
Nature Aging Jan 2024Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic...
Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of mechanisms responsible for this decline is limited. Glycerophosphocholine phosphodiesterase 1 (Gpcpd1) is a highly abundant muscle enzyme that hydrolyzes glycerophosphocholine (GPC). The physiological functions of Gpcpd1 remain largely unknown. Here we show, in mice, that the Gpcpd1-GPC metabolic pathway is perturbed in aged muscles. Further, muscle-specific, but not liver- or fat-specific, inactivation of Gpcpd1 resulted in severely impaired glucose metabolism. Western-type diets markedly worsened this condition. Mechanistically, Gpcpd1 muscle deficiency resulted in accumulation of GPC, causing an 'aged-like' transcriptomic signature and impaired insulin signaling in young Gpcpd1-deficient muscles. Finally, we report that the muscle GPC levels are markedly altered in both aged humans and patients with type 2 diabetes, displaying a high positive correlation between GPC levels and chronological age. Our findings reveal that the muscle GPCPD1-GPC metabolic pathway has an important role in the regulation of glucose homeostasis and that it is impaired during aging, which may contribute to glucose intolerance in aging.
Topics: Aged; Animals; Humans; Mice; Aging; Diabetes Mellitus, Type 2; Glucose; Metabolic Networks and Pathways; Muscle, Skeletal; Phospholipases; Glycerylphosphorylcholine
PubMed: 38238601
DOI: 10.1038/s43587-023-00551-6 -
Substance Use & Misuse 2024: Existing work proposes that people with higher social anxiety symptoms and sociability alcohol expectancies believe alcohol can lower their anxiety. However, studies...
: Existing work proposes that people with higher social anxiety symptoms and sociability alcohol expectancies believe alcohol can lower their anxiety. However, studies have primarily analyzed retrospective reports, not anticipatory motives. Since predictions of future emotion (i.e., affective forecasts) strongly influence behavior, it is critical to understand how people predict alcohol will influence their anxiety. Additionally, intolerance of uncertainty (IU) is related to the use of alcohol as a coping tool, but there is a dearth of work testing whether IU influences alcohol-related forecasts. : Utilizing a novel affective forecasting task, we tested the prediction that social anxiety symptoms, sociability alcohol expectancies, and IU would relate to predictions about alcohol use. In an initial study and preregistered replication, participants imagined themselves in stressful social scenarios and forecasted how anxious they would feel when drinking and when sober. In the replication, participants also forecasted whether they would drink in the imagined scenarios. : Contrary to hypotheses, social anxiety symptoms and IU did not significantly predict higher forecasted anxiety across studies, nor did they predict forecasted drinking. Exploratory analyses showed that participants with higher sociability alcohol expectancies forecasted being more likely to drink, and forecasted feeling less anxious when drinking (versus being sober). Even after statistically controlling for social anxiety, the effect of sociability expectancies remained significant in predicting forecasted anxiety and forecasted drinking. : Clinicians could consider specifically targeting sociability expectancies for alcohol use difficulties, and future research should continue utilizing affective forecasting paradigms to test links between social anxiety, alcohol expectancies, and alcohol-use problems.
Topics: Humans; Alcohol Drinking; Retrospective Studies; Anxiety; Social Behavior; Anxiety Disorders; Motivation
PubMed: 38233360
DOI: 10.1080/10826084.2024.2302133 -
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 -
Journal of Cataract and Refractive... Jan 2024A 70-year-old man had progressive and severe glaucoma in each eye. He was intolerant to dorzolamide, brimonidine, and netarsudil. Each eye had prior selective laser...
A 70-year-old man had progressive and severe glaucoma in each eye. He was intolerant to dorzolamide, brimonidine, and netarsudil. Each eye had prior selective laser trabeculoplasty (SLT) as well as phacoemulsification plus minimally invasive glaucoma surgery (MIGS) 6 years before current presentation (iStent [Glaukos Corp.] in the right eye and Cypass [Alcon Laboratories, Inc.] in the left eye). Postoperative acuities were 20/20 and 20/25 in the right and left eyes, respectively. When his left eye progressed with loss of central acuity despite peak intraocular pressures (IOPs) in the middle to upper teens, neuro-ophthalmology consultation was obtained (Figure 1JOURNAL/jcrs/04.03/02158034-202401000-00017/figure1/v/2023-12-22T124801Z/r/image-tiff). That workup included magnetic resonance imaging scan and hematologic screening, but all results were negative, and the neuro-ophthalmic consultant concluded that the vision loss was likely on the basis of glaucoma. Accordingly, a trabeculectomy was performed in the left eye achieving consistent IOPs in the range of 7 to 10 mm Hg without medications, rending the left eye stable since the filtration surgery nearly 2 years previously. The right eye continued to progress both subjectively and objectively, and on recent examination, the IOP measured 20 mm Hg and 09 mm Hg in the right and left eyes, respectively (Figure 2JOURNAL/jcrs/04.03/02158034-202401000-00017/figure2/v/2023-12-22T124801Z/r/image-tiff). Medications included timolol and latanoprostene bunod in the right eye only. Central corneal thickness was 526 μm and 527 μm in the right and left eyes, respectively. The visual acuity now measured 20/25 in the right eye and 20/250 in the left eye. The vertical cup-to-disc ratio was 0.9 in the right eye and 1.0 in the left eye. Gonioscopy revealed a wide open angle in each eye with a patent sclerostomy superiorly in the left eye. The conjunctiva and sclera were healthy and without scarring in the right eye. The bleb in the left eye was diffuse, lightly vascularized, and seidel negative. Axial length (AL) was 26.88 μm in the right eye and 26.77 μm in the left eye. The patient was in good health and was not anticoagulated. An extensive discussion ensued about the best course of action for the right eye. How would you proceed in managing definite progression in this individual's right eye, knowing that he had lost fixation in his left eye at similar pressures?
Topics: Male; Humans; Adolescent; Aged; Glaucoma; Trabeculectomy; Intraocular Pressure; Eye; Timolol
PubMed: 38133650
DOI: 10.1097/j.jcrs.0000000000001366 -
European Journal of Applied Physiology May 2024The purpose of this study was to compare the effects of fasting for 48 h on the evoked insulin and glucose responses in males and females, and to explore factors such as...
PURPOSE
The purpose of this study was to compare the effects of fasting for 48 h on the evoked insulin and glucose responses in males and females, and to explore factors such as stress and estrogen levels that might influence these responses.
METHODS
Healthy, nonobese male (n = 14) and female (n = 14) subjects underwent 48-h fasting trial. Changes in glucose tolerance and insulin levels in response to the oral glucose tolerance test, subjectively perceived stress and catecholamine concentrations were measured in all participants. Estrogen levels were also measured in the female participants during the 48-h fast.
RESULTS
Glucose area under the curve (AUC) values increased similarly in both sexes after 48-h fasting (P < 0.05), but females displayed a greater rise in insulin AUC values than males (P < 0.05). Fasting increased plasma epinephrine concentrations in both sexes (P < 0.05), whereas plasma norepinephrine concentrations and subjective stress increased only in females (P < 0.05). Plasma 17-β-estradiol concentrations in females decreased after fasting (P < 0.05).
CONCLUSION
Fasting for 48 h induced a similar glucose intolerance in females and males, despite decreased 17-β-estradiol levels and greater psychological and physiological stress in females. These differences represent a plausible explanation for the gender-based differences observed in insulin responses.
TRIAL REGISTRATION
Retrospectively registered on ClinicalTrials.gov (NCT05545943) in September 19, 2022.
Topics: Humans; Female; Male; Estradiol; Fasting; Adult; Glucose Intolerance; Blood Glucose; Stress, Psychological; Insulin; Epinephrine; Glucose Tolerance Test; Young Adult; Sex Factors
PubMed: 38108909
DOI: 10.1007/s00421-023-05378-y