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[Electrodiagnosis of neuromuscular diseases--a syndrome of monomelic amyotrophy with spinal hemiatrophy, anti-GM1 antibodies and abnormal F-waves (MASH)].

Electrodiagnosis rests upon sound anatomical and physiological bases of the peripheral nervous system, which are utilized for the dynamic process of differential diagnosis. If clinical and electrophysiological findings do not conform to any of the previously known diseases, there may be a chance of identifying a new entity. As an example, we report nine Japanese patients with unilateral atrophy of the distal upper limb and the cervical cord. Symptoms typically began insideously in young adulthood, progressed for a few years and then stabilized. Distribution of the muscle weakness usually corresponded to the territories of a few peripheral nerves, although not accompanied by sensory deficits. Serum anti-GM1 IgG antibodies were elevated in 6 out of 9 patients. Electrophysiological testings disclosed absent or delayed F-waves in the nerve involved. No long tract signs of the cord were demonstrated, although the spinal cord atrophy was extensive in some patients. Three showed partial clinical improvement after cyclophosphamide therapy or intravenous immunoglobulin. These findings may suggest that this entity is immune-mediated as in multifocal motor neuropathy, with its blunt of immune attack directed not only to peripheral motor nerves but also to spinal motor neurons.

Adolescent↗

Mobile surgical hospital design: lessons from 5th MASH surgical packages for Operations Desert Shield/Desert Storm.

Operations Desert Shield/Desert Storm defined and tested a number of assumptions about the abilities of the Mobile Army Surgical Hospital. These assumptions involved the adequacies of mobility, both strategic and tactical, the number of hospital beds, surgical capability, and set-up time. This article reviews the characteristics, staffing, and surgical abilities of the four types of surgical packages deployed by the 5th Mobile Army Surgical Hospital in response to the changing patient care and tactical situation. These packages were the Forward Surgical Team, Forward Surgical Element, Mobile Army Surgical Hospital(-), and Mobile Army Surgical Hospital. Seven variables as they relate to hospital weight and cubic space are introduced. Mobility and surgical ability are emphasized as the first and second highest priority to consider in a proposed methodology when developing Mobile Army Surgical Hospitals.

Middle East↗

[Toxicological and hygienic evaluation of a new fodder additive: liquid mash concentrate].

The results of toxicological evaluation of 'concentrate bardjanoj liquid' (CBL) a new fodder additive are presented. It was shown on one generation of rats that CBL at dose of 1 g and 10 g per 1 kg of body mass had no an embryotoxic, gonadotoxic and teratogenic effects. However long-term intake of CBL during 5 month with diet of rats caused the changes in rat body. It was found increasing of relative weights of kidney, spleen and heart, decreasing of contents of total lipids, phospholipids and cholesterol in rat liver. Also the desquamative enteritis in some cases with ulcers was found. These data did not allow to recommend CBL as fodder additive in studied doses.

Alanine Transaminase↗

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↗

Utilization of cassava peels as substrate for crude protein formation.

Mash prepared from cassava peels was inoculated with either Sacchromyces cerevisiae or Candida tropicalis and then left to ferment for 7 days. Chemical analysis of the fermented mash showed substantial increase in crude protein content and decrease in carbohydrate content of the mash. The results also revealed slight increases in the ash, fibre and lipid content of the fermented mash. It was further observed that, when the mash was supplemented with inorganic nitrogen sources (urea, ammonium sulfate or sodium nitrate) before commencement of fermentation, the amount of crude protein formed was almost doubled. This enhanced crude protein production was highest in the mash supplemented with urea. Temperature of 30 degrees C, pH of 5.5 and moisture concentration of 130% were found to be optimum for crude protein formation by the organisms growing on the mash.

Candida↗

Effect of choice feeding on the performance of broilers.

1. Male broilers from, 21 to 56 d of age were fed their diet either mixed as pellets or mash, or as separate ingredients presented on a free-choice basis, to determine whether feeding method affected growth, carcase composition or profitability to 56 d of age. 2. The 12 treatments were: 2 completely balanced diets fed as mash or pellets, 8 choice fed diets containing maize or sorghum as the energy source (whole or mash) and protein concentrate (pellets or mash) and 2 unbalanced mixed mash diets containing 50% grain (maize or sorghum) plus 50% protein concentrate. 3. For the choice treatments, one food, grain (maize or sorghum) or protein concentrate (mash or pellets), was placed in each feeder. Broilers fed the complete pelleted or mash diet received the diet in both feeders. Food consumption was recorded weekly. Broilers were weighed at 42 and 56 d of age. 4. There were no significant differences between treatments and the pelleted control diet with regard to body weight, food consumed, food efficiency, carcase, ash, dressing percentage and mortality. 5. Choice fed broilers receiving the energy source as whole grains had larger gizzards while the higher protein diets (50/50) resulted in a higher carcase moisture and protein but lower carcase fat than the broilers fed the pelleted control diet. 6. The main advantage of choice feeding appears to be the economical savings of feeding whole grains as the energy source.

Analysis of Variance↗

Palatable daily meals entrain anticipatory activity rhythms in free-feeding rats: dependence on meal size and nutrient content.

Circadian wheel-running rhythms were monitored continuously in 3 groups of female Sprague-Dawley rats under different palatable food availability schedules. All rats had free access to standard rat chow and water throughout the study. In addition, Group 1 rats received a palatable nutrient-rich mash for 2 hr each day for 28 days, beginning 3 hr after light onset of a 12:12 LD cycle. Group 2 rats received the same mash but were limited to 4 g daily. Group 3 rats received a palatable non-nutritive mash. Ten of 13 Group 1 rats, 2 of 13 Group 2 rats, and 0 of 13 Group 3 rats showed anticipatory running prior to the daily palatable meal. Palatable mash intake was generally lower among Group 3 rats than among Group 1 rats. However, several Group 3 rats consumed non-nutritive mash in amounts which equalled or exceeded the nutritive mash intake of Group 1 rats showing anticipatory running. The results indicate that temporally limited daily access to a palatable food can entrain anticipatory wheel-running in rats that are not food-deprived. They also indicate that entrainment to periodic food availability depends on stimuli associated with the concentrated intake of nutrients rather than on the absolute size or palatability of a meal.

Animals↗

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 &#x2265;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&#xb7;4 years (SD 10&#xb7;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&#xb7;8 [95% CI 7&#xb7;2-115&#xb7;2]; adjusted relative risk 6&#xb7;3 [95% CI 2&#xb7;5-15&#xb7;9]; p<0&#xb7;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↗

[NMR spectroscopy for studying structure and intramolecular dynamics of modified analogs of steroid hormones].

Special features of the use of homo- and heteronuclear correlation methods of NMR in one and two dimensions for studying the spatial structure and intramolecular dynamics of modified analogues of steroid hormones (MASH) are considered. The application of these methods to the assignment of resonances in the high-field 1H NMR region and to the determination of the most stereospecifically important parameters, such as the vicinal constants of spin-spin coupling (3JH-H) and nuclear Overhauser effects (NOE), are discussed using the example of NMR studies of some estrogens and androgens at 300 MHz and on the basis of literature data. The most efficient combination of the methods and the necessary modification of each of them may be chosen considering the spectral and relaxation parameters of MASH in liquid medium, including the anisotropy of the overall diffusive motion. The characteristics of MASH are the wide use of correlations through long-range couplings (COSY-45 and DQF-COSY), the application of the 4,5JH-H constants for the determination of spatial structure, and the advantage of heteronuclear HSQC methods with and without 13C decoupling over the corresponding HMQC methods in both resolution and sensitivity. In the conformationally rigid MASH molecules, the anisotropy of the MASH diffusive motion in liquid adversely affects the determination of interproton distances by the calibrating processing method for the NOE difference and NOESY spectra: it results in both overestimated and underestimated distance values depending on the polar angle ratios of the reference and the determined distances. Under certain conditions, conformationally mobile MASH demonstrate the additional contribution of the scalar relaxation mechanism between the indirectly (scalarly) bound protons. This mechanism is responsible for the underestimated values of NOE and the corresponding errors in the distance determination.

Androgens↗

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↗