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Disposal of sewage sludge creates the potential for heavy metal accumulation in the environment. This study assessed nine soils currentlyused as Dedicated Land Disposal units (DLDs) for treatment and disposal of municipal sewage sludge in the vicinity of Sacramento, California. Adsorption characteristics of these soils for Cd, Cu, Ni, Zn, Pb, and Cr were studied by simultaneously mixing these elements in the range of 0--50 mu mol L{sup}-1{end} with sludge supernatant and reacting with the soil using a soil:supernatant ratio of 1:30, pH = 4.5 or6.5, and constant ionic strength (0.01 M Na-acetate). The concentration of metals in the supernatant was determined after a 24 hr equilibration period. Adsorption isotherms showed that metal sorption was linearly related to its concentration in the supernatant solution. The distribution coefficient K{sub}d{end} (K{sub}d{end} conncentration onsolid phase/concentration in solution phase) was computed as the slope of the sorption isotherm. The distribution coefficients were significantly correlated to soil organic matter content for Ni, Cu, Cd, and Pb at pH 4.5 and for Ni, Cu, Zn, and Cd at pH 6.5. There was also acorrelation between K{sub}d{end} and soil specific surface area but no relationship to other soil properties such as CEC, clay content and noncrystalline Fe and Al materials. Therefore, soil organic carbon and surface area appear to be the most important soil properties influencing metal adsorption through formation of organo-metal complexes.The K{sub}d{end} values for all elements were higher at pH 6.5 than at 4.5. Selectivity between metals resulted in the following metal affinities based on their K{sub}d{end} values: Pb greater than Cu greater than Zn greater than Ni greater than Cd~~Cr at pH 4.5 and Pb greater than Cu~~Zn greater than Cd greater than Ni greater than Cr at pH 6.5. [ABSTRACT FROM AUTHOR]

Bone fractures are a prevalent clinical issue, and recent studies highlighted the promising potential of natural bone healing agents in enhancing fracture repair and regeneration. The regulatory interaction mechanism between osteoblasts and osteoclasts is crucial for bone cell biology and bone disease. In Mongolian medicine, people have used the Rhodiola rosea (R. rosea) extract to accelerate bone healing in bone fractures. Salidroside is a bioactive compound of R. rosea. Salidroside is known to regulate bone metabolism and inhibit the activation of osteoclast cells, but how it affects the differentiation of osteoclasts is unknown. We examined the effect of R. rosea extract and its bioactive compound salidroside on the RANKL-induced osteoclast formation in RAW 264.7 cells. The present study observed that salidroside directly inhibits RANKL-induced TRAP-positive osteoclast formation. Immunoblotting analysis revealed that salidroside inhibited the expression of c-Fos and NFATc1, osteoclastogenic key transcription factors, by suppressing late activation of p65 NFκB. Further, the ethanol extracts of R. rosea significantly reduced the RANKL-induced osteoclasts in a dose-dependent manner. In conclusion, salidroside inhibits RANKL-induced osteoclast formation via suppressing the NFκB/c-Fos/NFATc1 signalling pathway. R. rosea, a primary source of salidroside, is helpful for bone healing via its inhibitory effect on osteoclast formation., (© 2024. The Society for In Vitro Biology.)

Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the neuromuscular junction (NMJ) from motor neurons to skeletal muscle fibers. As a result, patients with MG have reduced skeletal muscle function and present with symptoms of severe muscle weakness and fatigue. ClC-1 is a skeletal muscle specific chloride (Cl - ) ion channel that plays important roles in regulating neuromuscular transmission and muscle fiber excitability during intense exercise. Here, we show that partial inhibition of ClC-1 with an orally bioavailable small molecule (NMD670) can restore muscle function in rat models of MG and in patients with MG. In severely affected MG rats, ClC-1 inhibition enhanced neuromuscular transmission, restored muscle function, and improved mobility after both single and prolonged administrations of NMD670. On this basis, NMD670 was progressed through nonclinical safety pharmacology and toxicology studies, leading to approval for testing in clinical studies. After successfully completing phase 1 single ascending dose in healthy volunteers, NMD670 was tested in patients with MG in a randomized, placebo-controlled, single-dose, three-way crossover clinical trial. The clinical trial evaluated safety, pharmacokinetics, and pharmacodynamics of NMD670 in 12 patients with mild MG. NMD670 had a favorable safety profile and led to clinically relevant improvements in the quantitative myasthenia gravis (QMG) total score. This translational study spanning from single muscle fiber recordings to patients provides proof of mechanism for ClC-1 inhibition as a potential therapeutic approach in MG and supports further development of NMD670.

Background: Conductive anaesthesia of the nerves around the head is one of the methods of intraoperative pain relief (under deep anaesthesia but before proceeding with the procedure). Performing this procedure on primates is especially challenging for the veterinarian, due to their cranial anatomy and topography, which has more in common with the human skull than with the skulls of other animals. Knowledge of key bony structures, including cranial foramina, is essential for effective anaesthesia of the cranial nerves., Results: In this study, the differences in the topography of the cranial foramina in eight selected species of primates were examined: Angola colobus (Colobus angolensis), Celebes crested macaque (Macaca nigra), L'Hoest's monkey (Allochrocebus lhoesti), baboon (Papio cynocephalus), buff-bellied capuchin (Sapajus xanthosternos), black-and-white ruffed lemur (Varecia variegata), crowned lemur (Eulemur coronatus), and a ring-tailed lemur (Lemur catta) coming from the Wroclaw Zoological Garden (Poland). The cranial nerves running through the foramina have also been described and their anaesthesia techniques against bone points have been tested to relieve post-operative pain in the area of the head supplied by these nerves., Conclusion: The tests carried out show differences in the topography of the cranial foramina, and therefore also differences in the methods of injection, so the results obtained in this study may be useful in veterinary medicine, especially for practising veterinarians., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aim: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS)., Background: A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades., Methods: Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations., Results: A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months., Conclusion: Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS., (©2021 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Aim: Young people with psychosis have higher rates of obesity, premature cardiovascular disease, and death compared to non-psychotic peers in the general population due to changes in metabolic regulation linked to antipsychotic medication and adverse health risk behaviors. The aim of this paper is to outline the development, implementation, and evaluation of a combined 12-week exercise and health behavior intervention delivered as part of an Early Intervention in Psychosis (EIP) routine service, within the UK., Methods: Participants (n = 27) completed a 12-week combined intervention program, engaging in weekly, 90-min sessions comprising a healthy behavior education session (45 min), followed by a facilitated exercise session (45 min). Anthropometric data from participants (n = 26) were collected at baseline, 12 weeks, and 12 months post-intervention. Health behaviors and clinical measurements were assessed at baseline and 12 months., Results: Mean baseline data suggests participants were at an increased health risk on entry to the program, with elevated values in mean body mass index (BMI; 70% overweight/obese), waist circumference, resting heart rate, and triglycerides. Fifty percent reported smoking daily, 64% ate < 5 fruits/vegetables per day, and 52% of participants were prescribed highly obesogenic antipsychotic medications (i.e., Olanzapine). At 12 weeks and 12 months, no changes were observed in mean BMI, waist circumference or any other clinical variable (p > 0.05). At 12 months, participants reported a positive impact on health behaviors including improved diet, increased physical activity levels, and cessation of substance use (n = 2), alcohol use (n = 2), and smoking (n = 4). Focus groups captured participant experiences, engagement with and satisfaction with the program, including challenges/barriers to program adherence., Conclusions: The 12-week exercise and health behaviors program supported participants to attenuate their physical health risk which was sustained at 12-month follow-up. Self-reported positive health behavior changes are likely to have contributed to the prevention of excessive weight gain in this high-risk period. The evaluation was designed to have validity for a "real world EIP setting" and reflect the complexity of delivery to this participant group. Evaluation findings influenced subsequent commissioning of the physical health intervention as an ongoing element of routine EIP care within the participant site., (Copyright © 2020 Smith, Griffiths, Band, Hird-Smith, Williams, Bold, Bradley, Dilworth and Horne.)

The current review aimed to synthesize the literature on the complex relationship between food consumption and nutritional status as well as the digestive system in order to examine the relationship between immunity and potential responses to COVID-19 infection. The goal is to help inform the many healthcare professionals working with COVID-19 patients. A literature search was performed on PubMed, Scopus, and EMBASE databases. Hand searches were also undertaken using Google and reference lists to identify recent evidence. Studies were critically appraised, and the findings were analyzed by narrative synthesis. Nutritional status can impact immunity in several ways, including affecting susceptibility to infection, severity of disease, and recovery time, and is therefore a significant consideration in the management of COVID-19. COVID-19 can also impact digestive function, which can further impact nutritional status. The role of Vitamin D deficiency in vulnerability to severe respiratory infections, including COVID-19, has been recognized, and it may have a role in treatment where deficiency is indicated. Healthcare professionals should be aware that obesity may be accompanied by micronutrient malnutrition including vitamin D deficiency and alterations in the microbiome and inflammatory responses, which can further impact immunity and disease severity. Multidisciplinary team-work is recommended in the management of patients with COVID-19, and approaches should include a consideration of nutritional status (both macronutrients and micronutrients), body weight, and gastrointestinal signs and symptom., (©2020 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Gluten elimination may represent an effective treatment strategy for mood disorders in individuals with gluten-related disorders. However, the directionality of the relationship remains unclear. We performed a systematic review of prospective studies for effects of gluten on mood symptoms in patients with or without gluten-related disorders. Six electronic databases (CINAHL, PsycINFO, Medline, Web of Science, Scopus and Cochrane Library) were searched, from inception to 8 August 2018, for prospective studies published in English. Meta-analyses with random-effects were performed. Three randomised-controlled trials and 10 longitudinal studies comprising 1139 participants fit the inclusion criteria. A gluten-free diet (GFD) significantly improved pooled depressive symptom scores in GFD-treated patients (Standardised Mean Difference (SMD) -0.37, 95% confidence interval (CI) -0.55 to -0.20; p < 0.0001), with no difference in mean scores between patients and healthy controls after one year (SMD 0.01, 95% CI -0.18 to 0.20, p = 0.94). There was a tendency towards worsening symptoms for non-coeliac gluten sensitive patients during a blinded gluten challenge vs. placebo (SMD 0.21, 95% CI -0.58 to 0.15; p = 0.25). Our review supports the association between mood disorders and gluten intake in susceptible individuals. The effects of a GFD on mood in subjects without gluten-related disorders should be considered in future research.

Aim: To explore the motivation for gluten avoidance in the absence of coeliac disease (CD) and ascertain what symptoms are triggered by gluten and what beliefs/reasons influence this decision., Background: Links between physical/psychological symptoms and gluten in CD are well known but less is known about those who self-select a gluten-free diet (GFD) in the absence of CD., Methods: An empirical study using responses to an anonymous on-line questionnaire. Closed questions were used as a screening tool to exclude participants who had CD, wheat allergy or were following a low FODMAP diet. Data from participants using a GFD in the absence of a medical diagnosis was then analysed using thematic analysis., Results: 120 initial responses, 87 were completed in full. 23 respondents fulfilled the inclusion criteria for thematic analysis. 7 different themes emerged, including one for signs/symptoms. Other themes identified included difficulties of a GFD, health beliefs, feelings and influence on decision to follow a GFD. Responses indicate that the reasons for gluten avoidance are in the most part reasoned and logical and were based around participants' self-management of symptoms., Conclusion: Symptoms included those typical of irritable bowel syndrome (IBS), but also infertility, low mood/energy, immune function and weight management and visual and auditory hallucinations. It appears the majority of responses analysed thematically could fit into the spectrum of non-coeliac gluten sensitivity (NCGS). Findings also suggest more support at all levels of medical care may help patients establish if it is gluten, rather than wheat or FODMAPs particularly fructans that are contributing to signs/symptoms.

Non-celiac gluten sensitivity (NCGS), also referred to as non-celiac wheat sensitivity (NCWS), is a clinical syndrome characterized by both intestinal and extra-intestinal symptoms responsive to the withdrawal of gluten-containing food from the diet. The aim of this review is to summarize recent advances in research and provide a brief overview of the history of the condition for the benefit of professionals working in gastroenterology. Academic databases such as PubMed and Google Scholar were searched using key words such as "non-celiac gluten sensitivity", "gluten related disorders", and the studies outlined in reference page were selected and analysed. Most of the analysed studiers agree that NCGS would need to be diagnosed only after exclusion of celiac disease and wheat allergy, and that a reliable serological marker is not available presently. The mechanisms causing symptoms in NCGS after gluten ingestion are largely unknown, but recent advances have begun to offer novel insights. The estimated prevalence of NCGS, at present, varies between 0.6 and 6%. There is an overlap between irritable bowel syndrome and NCGS with regard to the similarity of gastrointestinal symptoms. The histologic characteristics of NCGS are still under investigation, ranging from normal histology to slight increase in the number of T lymphocytes in the superficial epithelium of villi. Positive response to gluten free diet for a limited period (e.g., 6 weeks), followed by the reappearance of symptoms after gluten challenge appears, at this moment, to be the best approach for confirming diagnosis. The Salerno expert criteria may help to diagnose NCGS accurately in particular for research purposes but it has limited applicability in clinical practice.

To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day 8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6-10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects. Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells, which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence would be useful to examine the effects of valproic acid on the somitogenesis and morphogenesis of somite-associated structures.

Aim: To assess the clinical characteristic of CD as well as correlation of symptoms and the degrees of intestinal mucosal lesions in Iranian children., Background: Microscopic Enteritis (Marsh 0-II) is associated with malabsorption., Patients and Methods: From August 2005 to September 2009, 111 cases with malabsorption and classical gastrointestinal symptoms were evaluated., Results: The mean (±SD) age of children with CD was 4.9±3.5 years (range, 6 month - 16 years) and the mean duration of symptoms was 8 ± 20.5 months. 50 cases (45%) were female and 61 cases (55%) were male. The most common clinical presentation was failure to thrive in 72%, chronic diarrhea in 65.8% and Iron deficiency anemia in 59.5%. Sensitivity of EMA was 100% in patients with Marsh IIIb and Marsh IIIc. EMA was also positive in 77% of cases with Marsh 0, 18% in Marsh I, 44% in Marsh II and 81.8% in patients with Marsh IIIa., Conclusion: Histopathology did not reflect the severity of gluten sensitivity. This would suggest that the degree of intestinal mucosal damage might not be a reliable prognostic factor. Significant symptoms can be present with minor histological change on biopsy.

Tolerable gluten thresholds in gluten free products have long been debated together with issues of cross contamination of gluten free cereals during the milling process. It is well established that a totally gluten free diet is virtually impossible owing to the presence of traces of gluten. It is estimated that daily consumption of gluten from contaminated gluten free foods is in the range of 5 to 50 mg. We believe evidence is mounting that it may be possible for some coeliac patients to tolerate gluten above the limits considered permissible at threshold levels. Conversely, it seems there is evidence that some patients might have a much lower threshold for gluten. Whatever would be the individual threshold, GFD may be of benefit to any symptomatic patients even those with milder enteropathy like microscopic enteritis.

Aim: The purpose of this study is to explore whether the types and quality of breakfast could influence energy levels (blood glucose levels) and propose ideal breakfast models., Background: It is widely considered that a regular breakfast provides a number of health benefits; however, there is no general scientific agreement regarding what kind of food should be consumed. Evidence supports the importance of balancing blood glucose levels by low glycaemic index/load (L-GI/L) and increased protein diets, in particular in metabolic disorders, which non-alcoholic fatty liver disease (NAFLD) has a close relation to., Patients and Methods: This study was conducted by using a valid and standard questionnaire at the University of Worcester to evaluate the breakfast and dietary habits and energy levels. The Kruskal-Wallis test was used for statistical analysis., Results: No significant differences were found either between breakfast consumption, energy levels, types of snack and amount of caffeine intake in the morning or between types of breakfast, energy levels, types of snack, and amount of caffeine intake in the morning. However, potential differences in energy levels were found across the groups of breakfast types: glycaemia (GL) (p=.057) and protein intake (p=.056)., Conclusion: The types and quality of breakfast would be key as regular breakfast consumption alone did not show adequate health benefits. Lower GL foods and higher protein intake at breakfast were found to be associated with higher energy levels. It is therefore recommended that breakfast foods should be low in GL and high in protein. These changes may lead to better health status and prevention of disease, especially metabolic and liver disorders, in the long term.

Aggregation of cell surface receptors by multivalent ligand can trigger a variety of cellular responses. A well-studied receptor that responds to aggregation is the high affinity receptor for IgE (FcepsilonRI), which is responsible for initiating allergic reactions. To quantify antigen-induced aggregation of IgE-FcepsilonRI complexes, we have developed a method based on multiparameter flow cytometry to monitor both occupancy of surface IgE combining sites and association of antigen with the cell surface. The number of bound IgE combining sites in excess of the number of bound antigens, the number of bridges between receptors, provides a quantitative measure of IgE-FcepsilonRI aggregation. We demonstrate our method by using it to study the equilibrium binding of a haptenated fluorescent protein, 2,4-dinitrophenol-coupled B-phycoerythrin (DNP25-PE), to fluorescein isothiocyanate-labeled anti-DNP IgE on the surface of rat basophilic leukemia cells. The results, which we analyze with the aid of a mathematical model, indicate how IgE-FcepsilonRI aggregation depends on the total concentrations of DNP25-PE and surface IgE. As expected, we find that maximal aggregation occurs at an optimal antigen concentration. We also find that aggregation varies qualitatively with the total concentration of surface IgE as predicted by an earlier theoretical analysis.

The actions of nicotinamide and inosine were investigated on rat cerebellar Purkinje cells using ionophoretic and extracellular recording techniques. Ionophoretic application of nicotinamide or inosine showed that they were potent inhibitors of Purkinje cell firing. This inhibition differed from that induced by benzodiazepines in that it was not reversed by the GABA antagonists bicuculline methiodide and picrotoxin. RO 15-1788, the specific benzodiazepine antagonist, did not reverse the effects of nicotinamide. Chlordiazepoxide has been shown to increase significantly social interaction between pairs of male rats and this increase can be reversed by RO 15-1788, 20 mg kg-1 i.p. Nicotinamide also caused a small increase in social interaction but this effect was not reversed by the benzodiazepine antagonist. Inosine did not increase social interaction. [3H]-flunitrazepam binding studies showed that nicotinamide and inosine have only low affinities for the benzodiazepine binding site. These results suggest that while nicotinamide may exert some neuronal depressant and anxiolytic activity, its site of action appears not to be associated with the benzodiazepine receptor site. Similarly, inosine exerts a neuronal depressant effect dissimilar from that of benzodiazepines.

Intracellular recordings were made from central Limulus and Helix neurones and extracellular recordings from rat cerebellar Purkinje cells and sympathetic ganglia. The actions of gamma-aminobutyric acid (GABA) and ethylenediamine (EDA) and related analogues on these preparations were investigated. On Limulus neurones inhibited by GABA, EDA and piperazine were 81 and 186 times respectively less potent than GABA. Both the GABA and EDA events were chloride mediated, having similar reversal potentials and were reversibly antagonised by picrotoxinin. The EDA response persisted in high magnesium Ringer. On Helix neurones inhibited by GABA, EDA was 92 times less potent while on neurones excited by GABA, EDA was 9.25 times less potent. The other analogues tested had little or no GABA-like effect on either preparation. On rat cerebellar Purkinje cells, EDA was equipotent with GABA and both compounds were antagonised by bicuculline. Flurazepam only potentiated the action of EDA on 3 out of 23 cells tested while the GABA response of all 23 cells was potentiated by the benzodiazepine. Diaminopropionic acid was a weak inhibitor of cerebellar Purkinje cell firing but flurazepam potentiated this response in 6 out of 10 cells tested. On rat cervical ganglion neurones, EDA was half the potency of GABA and likewise the other analogues were less potent than GABA as depolarising agents. Incubation with glutamic acid decarboxylase inhibitors had no effect on the EDA response. Cross desensitisation between GABA and EDA was demonstrated using the ganglion preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

In the first experiment ovariectomized female hamsters were administered varying dosages of progesterone (P), dihydrotestosterone (DHT) or CI-628 at the same time (concurrently) as estrogen (EB) or 48 hr after EB (sequentially). All groups also received 500 microgram P 4 hr before being tested for sexual receptivity. P was more effective in reducing receptivity when given sequentially with estrogen than when given concurrently. Thus, the inhibitory effect of P increased with an increased interval between EB and P treatment. More CI-628 than P was required to inhibit lordosis and unlike P, CI-628 was equally effective when given concurrently with EB as when given sequentially. DHT did not inhibit receptivity when given in either paradigm. In the second experiment ovariectomized hamsters were treated with varying dosages of DHT 12 hr before EB. An amount of DHT which had no effect in Experiment 1 significantly inhibited receptivity when given 12 hr before EB. The relative inhibitory effects of these three compounds were discussed in terms of the possible similarities and differences in their mechanisms of action for inhibiting lordosis.