Analysis of the results of parasitological investigations requested for patients attending the Shah-Reza Medical Center, Mash'had, Iran.
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Female↗
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Results for “MASH”
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Genome-wide DNA methylation profiling during metabolic dysfunction-associated steatohepatitis-related hepatocarcinogenesis in patients in Japan and the United States.
This study aimed to compare ethnicity-related differences in DNA methylation profiles during metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocarcinogenesis in patients from Japan and the United States (US). Genome-wide DNA methylation analysis using the Infinium assay was performed in 36, 148 and 36 samples of normal liver tissue (NLT), non-cancerous liver tissue showing MASH, and MASH-related hepatocellular carcinoma (HCC), respectively (220 samples in total), from the Japan and US cohorts. Principal component analysis revealed that MASH had a distinct DNA methylation profile differing from that of NLT, and that the MASH profiles in the two cohorts differed from each other. DNA methylation alterations of cancer-related genes in MASH were inherited by or strengthened in MASH-related HCC itself, resulting in expression alterations. DNA methylation alterations of FGFR2, FUT4, B3GNT5 and MOSC1 in the precancerous MASH stage were shared by the two cohorts, suggesting that such genes are commonly associated with MASH-related hepatocarcinogenesis. On the other hand, it was suggested that DNA methylation alterations of ZNF611 and SAMD10, and those of SHC1, are involved specifically in MASH-related hepatocarcinogenesis in the Japan and the US cohorts, respectively. These findings suggest that DNA methylation alterations, which may reflect race and lifestyle, are associated with MASH-related hepatocarcinogenesis.
Humans↗
Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.
BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase ≥ 2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2 = 75.6%, τ2 = 0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2 = 0%, τ2 = 0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2 = 70.2%, τ2 = 0.561) in MASH F3, with significant differences between stages (p = 0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.
Humans↗
Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis.
Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. Here we show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation and reduced hepatic expression of fibrosis-related and inflammation-related gene pathways. Aptamer-based proteomic analyses of serum samples from patients with MASH in a clinical trial identified 72 proteins significantly associated with MASH resolution and semaglutide treatment, with most related to metabolism and several implicated in fibrosis and inflammation. An independent real-world cohort verified the pathophysiological relevance of this signature, showing that the same 72 proteins are differentially expressed in patients with MASH relative to healthy individuals. Taken together, these data suggest that semaglutide may revert the circulating proteome associated with MASH to the proteomic pattern observed in healthy individuals.
Humans↗
The glucagon and GLP-1 receptor dual agonist DD01 for metabolic dysfunction-associated steatotic liver disease and steatohepatitis (DD01-DN-02): 12-week results from a randomised, double-blind, multicentre, placebo-controlled, phase 2 trial.
BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a major public health problem arising in the context of metabolic syndrome and obesity. DD01 is a liver-targeted GLP-1 receptor and glucagon dual agonist being investigated for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH. The DD01-DN-02 trial aimed to evaluate the efficacy and safety of DD01 in adults with MASLD or MASH; this initial analysis reports prespecified 12-week outcomes to assess early hepatic effects. METHODS: DD01-DN-02 is an ongoing, randomised, double-blind, multicentre, placebo-controlled, phase 2 trial conducted at 12 outpatient clinical sites in the USA. Adults aged 18-70 years with obesity or who were overweight (BMI ≥25 kg/m2) were included in the study. Patients with MASLD or MASH underwent liver biopsy and MRI-proton density fat fraction (PDFF) and were eligible if liver fat content was 10% or higher with metabolic risk factors, or if the biopsy confirmed MASH with a non-alcoholic fatty liver disease activity score of at least 4. Participants were randomly assigned (1:1) to receive once-weekly subcutaneous DD01 40 mg or matched placebo over 48 weeks, dose-escalated over 2 weeks, using a centrally administered interactive response technology system. The randomisation sequence was computer-generated by an independent statistician. Participants, investigators, study staff, outcome assessors, and the sponsor were masked to treatment assignment. The primary endpoint was the proportion of participants having at least a 30% relative reduction in liver fat by MRI-PDFF at week 12, which was analysed in all randomly assigned participants receiving at least one dose of study drug or placebo. Safety analyses included all participants who received at least one dose of study drug. Missing primary endpoint data were handled using multiple imputation under a missing-at-random assumption. This trial is registered with ClinicalTrials.gov (NCT06410924) and is ongoing but closed to new participants. FINDINGS: Between June 13, 2024, and Jan 30, 2025, 67 eligible participants were enrolled, of whom 33 were randomly assigned to DD01 and 34 to placebo. The mean age of participants was 48·4 years (SD 10·6), 42 (63%) were female, 25 (37%) were male, 57 (85%) were White, and 52 (78%) participants had biopsy-confirmed MASH. At week 12, 25 (76%) of 33 participants receiving DD01 had a 30% or higher reduction in liver fat versus four (12%) of 34 participants receiving placebo (adjusted common odds ratio 28·8 [95% CI 7·2-115·2]; adjusted relative risk 6·3 [95% CI 2·5-15·9]; p<0·0001). Treatment-emergent adverse events occurred in 28 (85%) of 33 participants receiving DD01 and 23 (68%) of 34 participants receiving placebo. The most common adverse events were nausea (18 [55%] of 33 participants assigned DD01; six [18%] of 34 participants assigned placebo), diarrhoea (nine [27%] of 33; six [18%] of 34), and vomiting (ten [30%] of 33; four [12%] of 34). Treatment-emergent adverse events led to treatment discontinuation in four (12%) of 33 participants in the DD01 group and one (3%) of 34 participants in the placebo group. Two (6%) treatment-emergent serious adverse events occurred in the DD01 group (abdominal pain and acute cholecystitis) and zero in the placebo group. No deaths occurred. INTERPRETATION: In this prespecified 12-week primary analysis, DD01 produced rapid reductions in liver fat compared with placebo, supporting further evaluation in long-term studies. FUNDING: D&D Pharmatech, Neuraly.
Humans↗
Dissociation of gustatory and weight regulatory responses to quinine following lateral hypothalamic lesions.
In a two-phase experiment, consummatory (Phase 1) and body weight regulation (Phase 2) responses to quinine adulteration of a wet mash diet were measured in rats recovered from bilateral lateral hypothalamic lesions (LH; n = 16) and in unoperated control rats (C; n = 18). In Phase 1, all rats were fed wet mash adulterated with increasing concentrations of quinine sulfate every other day, and fed unadulterated wet mash on the alternate days. Group LH consumed a significantly lower proportion of quinine-adulterated wet mash relative to unadulterated wet mash, displaying a steeper concentration-response function and a lower rejection threshold than did Group C. In Phase 2, Groups LH and C were maintained exclusively on quinine-adulterated mash for 20 days. This procedure caused equivalent weight loss in the two groups. Therefore, an apparent exaggerated aversion to quinine-adulterated food does not appear to contribute abnormally to the weight regulation exhibited by rats with lateral hypothalamic damage.
Animals↗
What consistency of food is best for children with cerebral palsy who cannot chew?
Video recordings were made of 67 children with cerebral palsy and 64 able bodied children eating soft boiled ('non-mashed') and mashed potato. Those children with cerebral palsy who had no speech, presumed to have poor oral motor function, took significantly longer to eat non-mashed than mashed potato. Children with cerebral palsy, especially those with no speech, were more likely to cough or choke while eating non-mashed than mashed potato. It is recommended that children with cerebral palsy who have poor oral motor function are offered food that they can eat with the least frustration or distress. This may also improve their dietary intake and state of nutrition.
Adolescent↗
Decreased reactivity to sweetness following chronic exposure to mild unpredictable stress or acute administration of pimozide.
Consumption of a palatable wet mash was examined in rats subjected chronically (4-10 weeks) to unpredictable mild stress. Intake of mash containing 0, 10%, or 20% additional sucrose was normal in stressed animals. In control animals, the addition of 30% or 40% sucrose caused a decrease in the quantity of mash consumed, but increased the rate of eating. Both the increase in eating rate and the decrease in intake, at high sucrose concentration, were markedly attenuated in stressed animals (which therefore had higher intakes of very sweet mash and lower rates of eating, relative to control animals). Like chronic mild stress, the dopamine receptor antagonist pimozide (0.2 mg/kg) also increased the intake of a wet mash with 30% added sucrose, while decreasing the rate of consumption. Stressed animals were relatively insensitive to pimozide, though there were significant additive effects on duration of eating (increased) and on postprandial resting (suppressed). The failure of stressed animals to adapt their intake to increases in sweetness, and the similarities between the effects of chronic mild stress and acute pimozide, are compatible with the hypothesis that animals exposed to chronic mild stress are anhedonic.
Animals↗
Hepatocyte-Specific Deficiency of Endoplasmic Reticulum-Associated Degradation Induces Coordinated Innate-Adaptive Immune Responses.
Hepatic inflammation is a defining feature of Metabolic Dysfunction-Associated Steatohepatitis (MASH), yet the specific contributions of individual immune cell populations and their reciprocal interactions remain incompletely understood. In this study, we combined flow cytometry with single-cell transcriptomic profiling to characterize the hepatic immune landscape in a novel model of spontaneous MASH caused by hepatocyte-specific deficiency of endoplasmic reticulum-associated degradation (ERAD). Hepatic ERAD deficiency led to the expansion of multiple immune cell populations in the liver, including CD8+ T cells, macrophages, monocytes, and dendritic cells, accompanied by extensive functional reprogramming of both innate and adaptive immune compartments. Myeloid cells exhibited enhanced phagocytic activity and increased antigen processing and presentation, whereas CD8+ T cells displayed elevated proliferation capacity, DNA repair activity and cytotoxicity. Notably, two functionally distinct triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophage subsets emerged during the progression of ERAD deficiency-induced MASH. Depletion of CD8+ T cells increased monocyte infiltration and aggravated liver injury, suggesting that CD8+ T cells exert a previously unrecognized protective role by restraining monocyte recruitment. Collectively, these findings reveal highly coordinated interactions between innate and adaptive cells during MASH progression and identify CD8+ T cells as potential regulators of monocyte infiltration and hepatic injury.
Animals↗
The technique of death masks making.
In taking death-masks two different techniques are used. In the technique using a plaster matrix the plaster mash is brought on the face. When the plaster-cast has dried it is filled with plaster mash. Later the matrix is removed in order to lay open the mask. In the technique using a plastic matrix the plastic powder Palgat is brought on the face after mixing it rapidly with icewater until it appears pappy. After that a layer of several centimeters of plaster mash follows in order to stabilize the delicate plastic matrix. Likewise the matrix is filled with plaster mash. The mask can be furnished with a collar and a fixation and the surface can be prepared. The skin relief of the face is reproduced finer using the cast of a plastic matrix.
Cadaver↗
Monoclonal antibody solution hybridization assay for detection of mouse hepatitis virus infection.
A monoclonal antibody solution hybridization (MASH) assay was developed to detect fecal excretion of mouse hepatitis virus (MHV). The assay used a biotinylated cDNA probe to detect viral RNA target sequences by hybridization in solution, capture of hybrids on the solid phase with antibiotin antibody, and immunoassay with an enzyme-labelled monoclonal antibody specific for DNA-RNA hybrids. The MASH assay was used to monitor the time course of enterotropic MHV excretion after oronasal inoculation. Infectivity of the inoculated mice was simultaneously monitored with sentinel animals. The MASH assay detected MHV excretion in all inoculated mice, with the highest mean excretion levels occurring from day 3 through day 9 postinoculation. Mean excretion then decreased gradually to below detection limits by day 21 postinoculation. Sentinels became infected on exposure to inoculated mice up to but not after day 21 postinoculation. Infected sentinel mice showed a time course of virus excretion similar to that of inoculated mice. These results indicate that the MASH assay is useful for rapid, sensitive, and specific detection of MHV in clinical specimens from laboratory mice.
Animals↗
[Effects of sodium chloride on destruction of microorganisms by microwave heating in potatoes].
To assess the destructive effect of different sodium chloride concentrations (0, 0.3, 1.5, and 3%) on microorganisms with microwave heating, strains of Vibrio parahaemolyticus, Staphylococcus aureus, Salmonella enteritidis, Escherichia coli and Bacillus cereus were used to inoculate a mashed potato preparation. After microwave heating for 1 min at 800 W, resulted in temperatures and rate of destruction of bacteria significantly higher (p less than 0.05) in the core than on the surface of mashed potato when no salt was added. Except for B. cereus, microorganisms inoculated into mashed potato, with no added salt, could be completely destroyed by 2 min of microwave heating. Core temperatures and rate of destruction of microorganisms in the mashed potato decreased significantly (p less than 0.05) with increase in concentration of added salt. The results also indicate that bacterial species differ in their susceptibility to microwave inactivation. In particular, S. aureus, which exhibited a level of survival that was greater than that of any other species tested here, seemed notably resistant to microwave treatment for 2 min while V. parahaemolyticus was highly susceptible.
Bacteria↗
Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction-Associated Steatohepatitis-Reanalysis of Fibrosis Stage 2-3 Subset.
BACKGROUND: Resmetirom is an oral thyroid hormone receptor beta agonist clinically used to treat metabolic dysfunction-associated steatohepatitis (MASH) among adults with stage F2 or F3 fibrosis. AIMS: Because the pivotal, 52-week, randomized, controlled, phase 3 MAESTRO-NASH trial (once-daily oral resmetirom 80 or 100 mg or placebo) included patients with F1, F2, or F3 fibrosis, we conducted a post hoc analysis aimed at assessing treatment response in the subset of patients with stages F2 and F3 fibrosis, consistent with the approved label population. METHODS: Co-primary end points were MASH resolution (hepatocellular ballooning score 0, lobular inflammation score ≤ 1, and ≥ 2-point nonalcoholic fatty liver disease activity score [NAS] reduction from baseline) with no fibrosis worsening, and ≥ 1-stage fibrosis improvement with no NAS worsening at Week 52. RESULTS: Among 917 patients with F2 or F3 fibrosis, metabolic risk factor prevalence was high (hypertension, 78.0%; dyslipidemia, 71.1%; type 2 diabetes, 67.0%). MASH resolution was achieved by 25.7% in the 80-mg group, 29.9% in the 100-mg group, and 9.5% in the placebo group (p < 0.0001 for both comparisons with placebo). Respective percentages with fibrosis improvement were 26.5%, 28.9%, and 17.3% (p < 0.01 for both comparisons). From baseline to Week 24, low-density lipoprotein cholesterol decreased by 11.7% and 13.7% in the 80- and 100-mg resmetirom groups, respectively, and increased by 2.3% with placebo (p < 0.0001 for both comparisons). No new safety signals emerged. CONCLUSION: Results among patients with F2 and F3 fibrosis were consistent with the primary MAESTRO-NASH analysis population, demonstrating efficacy and safety of resmetirom after 52 weeks.
Humans↗
The effect of dietary sodium fluoride on internal organs, breast muscle, and bones in captive American kestrels (Falco sparverius).
In 1982, 29 7-day-old American kestrel (Falco sparverius) chicks from captive stock were randomly assigned to one of three dietary regimens: (1) 10 birds were fed daily with cockerel mash (0 ppm of F-: control birds); (2) 10 birds were fed daily with cockerel mash containing 1,120 ppm of F-; (3) 9 birds were fed daily with cockerel mash containing 2,240 ppm of F-. Growth of the kestrels was not significantly affected by NaF in their diet. No significant differences were found among the 3 groups for length of duodenum, jejunum and ileum. Rectum was longer as more fluoride was added to the diet. Weights of adrenals, brain, gizzard, spleen, heart, kidneys, liver, pancreas, and pectoral muscle were not significantly affected by treatment, although kidneys, spleen and adrenals tended to become lighter. Percent bone ash was significantly (P less than 0.05) increased, while bone breaking strength was significantly (P less than 0.05) decreased by treatment.
Animals↗
Low doses of the 5-HT1A receptor agonist 8-OH-DPAT increase ingestive behavior in late preweanling and postweanling, but not neonatal rat pups.
Late preweanling (postnatal day 17-18; P17-18) and postweanling (P28-29) Sprague-Dawley rat pups were tested in the presence of both mash and liquid diets following s.c. administration of 0, 0.03, 0.06, 0.1 or 0.5 mg/kg of the 5-HT1A receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Preweanling pups exhibited both a low dose stimulatory and high dose depressant effect of 8-OH-DPAT on mash-related ingestive behaviors, whereas postweanling rat pups were less sensitive to 8-OH-DPAT, exhibiting only an increase in mash ingestion within the dose range examined. In contrast, when neonatal (P3-4) rat pups were tested with milk across a dose range of 0.001-1.0 mg/kg 8-OH-DPAT, no increases in ingestion were seen, with lower doses in this range having no detectable effects and higher doses decreasing ingestion and mouthing. To the extent that low doses of 8-OH-DPAT increase feeding via preferential stimulation of 5-HT1A autoreceptors, these data suggest that neonates may lack functional 5-HT1A autoreceptors, with these receptors maturing by the late preweanling period.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Stability of aflatoxin B-1 and ochratoxin A in brewing.
The stability of aflatoxin B-1 and ochratoxin A in brewing was investigated by adding the purified toxins to the raw materials at 1 and 10 mug/g levels during mashing in a conventional micro-brewing process. The results indicate that both toxins are stable to heat and are insensitive to cooker mash treatment. Both mycotoxins were partially removed in the mashing and brewing processes. About 14 to 18% and 27 to 28% of the added toxins were found in the final beers brewed from starting materials containing 1 and 10 mug, respectively, of either toxin per g. The possible route of transmission of mycotoxins into beer is discussed.
Aflatoxins↗
Calcium and carbonate supply in the shell gland of hens laying eggs with strong and weak shells and during and after a rest from lay.
The concentration of calcium-binding protein (CaBP) and the activities of calcium adenosine triphosphatase (Ca(2+)-ATPase) and carbonic anhydrase (CA) were determined in the shell gland mucosa of hens in two experiments. In Experiment 1, laying hens on a proprietary layer mash were compared with hens rested from lay by the feeding of whole grain barley. In Experiment 2 comparisons were made of laying hens fed the proprietary layer mash and producing eggs with either strong or weak shells. These latter comparisons were also made when the shell gland was quiescent or active with respect to daily eggshell formation. Feeding whole grain barley reduced egg production to zero after 11 days. This reduction in rate of lay was accompanied by significant reductions in all three markers, the effect on Ca(2+)-ATPase and CaBP being less than for CA. Control values were regained between 10 and 16 days after the barley was replaced with the layer mash. Relative shell strength and the physiological status of the shell gland with respect to time of daily eggshell formation had no significant effect on any marker in Experiment 2.
Animal Feed↗
Training resident surgeons in combat: an experience during the Persian Gulf War.
The Persian Gulf War necessitated the activation of many Army Reserve and National Guard physicians, including a number in residency training. No prototype existed for the continued training of resident surgeons in a combat setting. The 159th Mobile Army Surgical Hospital (MASH) deployed in support of the Allied invasion of Iraq. A structured training program for two general surgery residents attached to the 159th MASH was developed and implemented. This program combined supervised operating room experience, perioperative management, morbidity and mortality conferences, and orthopedic grand rounds, all with careful professional documentation. A planned reading program could not be realized, due to the physical setting of wartime. Residents and attending staff interacted positively and the residents were able to continue their formal training as an integral part of the hospital. The model developed by the 159th MASH is a practical method of continuing structured resident training in a combat setting.
General Surgery↗