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Background: The World Health Organization recommends universal iron supplementation for children aged 6-23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation., Methods: This will be a two-arm, randomised controlled trial. Gambian children aged 6-12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 mg of elemental iron as haem or ferrous sulphate. Safety outcomes such as diarrhoea and infection-related adverse events will be assessed daily by the clinical team (see Bah et al. Additional file 4_Adverse event eCRF). Linear regression will be used to analyse continuous outcomes, with log transformation to normalise residuals as needed. Binary outcomes will be analysed by binomial regression or logistic regression, Primary analysis will be by modified intention-to-treat (i.e., those randomised and who ingested at least one supplement dose of iron), with multiple imputations to replace missing data. Effect estimates will be adjusted for baseline covariates (C-reactive protein, alpha-1-acid glycoprotein, haemoglobin, ferritin, soluble transferrin receptor)., Discussion: This study will determine if therapeutic supplementation with haem iron is more efficacious than with conventional ferrous sulphate in enhancing haemoglobin and ferritin concentrations in anaemic children aged 6-12 months., Trial Registration: Pan African Clinical Trial Registry PACTR202210523178727., (© 2024. The Author(s).)

Intoxications with organophosphorus compounds (OPCs) effect a severe impairment of cholinergic neurotransmission that, as a result of overstimulation may lead to desensitization of nicotinic acetylcholine receptors (nAChRs) and finally to death due to respiratory paralysis. So far, therapeutics, that are capable to address and revert desensitized neuromuscular nAChRs into their resting, i.e. functional state are still missing. Still, among a class of compounds termed bispyridinium salts, which are characterized by the presence of two pyridinium subunits, constituents have been identified, that can counteract organophosphate poisoning by resensitizing desensitized nAChRs. According to comprehensive modeling studies this effect is mediated by an allosteric binding site at the nAChR termed MB327-PAM-1 site. For MB327, the most prominent representative of the bispyridinium salts and all other analogues studied so far, the affinity for the aforementioned binding site and the intrinsic activity measured in ex vivo and in in vivo experiments are distinctly too low, to meet the criteria to be fulfilled for therapeutic use. Hence, in order to identify new compounds with higher affinities for the MB327-PAM-1 binding site, as a basic requirement for an enhanced potency, two compound libraries, the ChemDiv library with 60 constituents and the Tocriscreen Plus library with 1280 members have been screened for hit compounds addressing the MB327-PAM-1 binding site, utilizing the [ 2 H 6 ]MB327 MS Binding Assay recently developed by us. This led to the identification of a set of 10 chemically diverse compounds, all of which exhibit an IC 50 value of ≤ 10 µM (in the [ 2 H 6 ]MB327 MS Binding Assay), which had been defined as selection criteria. The three most affine ligands, which besides a quinazoline scaffold share similarities with regard to the substitution pattern and the nature of the substituents, are UNC0638, UNC0642 and UNC0646. With binding affinities expressed as pK i values of 6.01 ± 0.10, 5.97 ± 0.05 and 6.23 ± 0.02, respectively, these compounds exceed the binding affinity of MB327 by more than one log unit. This renders them promising starting points for the development of drugs for the treatment of organophosphorus poisoning by addressing the MB327-PAM-1 binding site of the nAChR., Competing Interests: Declaration of Competing Interest Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons., Methods: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling., Results: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not., Conclusions: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the effects of triple beaded mixed amphetamine salts (TB MAS) on ADHD and executive dysfunction symptoms throughout the day in adults with DSM-5 ADHD., Method: This was a 6 week, single-blind, placebo-lead in trial of TB MAS (12.5-37.5 mg/day); all participants received 2 weeks of single-blind placebo); one individual was a placebo responder and was discontinued. One of these 18 dropped after 1 week on 12.5 mg/day, while all others completed the trial and received 37.5 mg/day TB MAS., Results: There were significant effects of TB MAS on all clinical measures, including investigator overall symptoms (AISRS); self-report overall (ASRS), time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A). TB MAS was generally well tolerated., Conclusions: This study extends prior findings of TB MAS to adults with DSM-5 ADHD; it further re-validates findings of efficacy of TB MAS throughout the day., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: 3 year Disclosures: Lenard A. Adler MD: has received Grant/Research support to NYU Grossman School of Medicine from Shire/Takeda, Otsuka Pharmaceuticals, Corium; Consultant to Supernus Pharmaceuticals, Bracket/Signant, SUNY, Neurocentria, National Football League, Major League Baseball, Otsuka; Royalty payments (as inventor) from NYU Grossman School of Medicine for license of adult ADHD scales and training materials since 2004.; Deepti Anbarasan MD, Taylor Sardoff BA, Terry Leon RN, Caleb A. Massimi BA have all declared no potential conflicts of interest; 3 year Disclosures: Richard Gallagher Ph.D:Research Support from NIMH and IES; Royalties from Guilford Press and NYU Grossman School of Medicine (latter for Children’s Organizational Skills Scale Project).; In the past year, Dr. Faraone received income, potential income, travel expenses continuing education support and/or research support from Aardvark, Aardwolf, AIMH, Tris, Otsuka, Ironshore, Kanjo, Johnson & Johnson/Kenvue, KemPharm/Corium, Akili, Supernus, Atentiv, Noven, Sky Therapeutics, Axsome and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.ADHDEvidence.org and www.ADHDinAdults.com. Dr. Faraone is supported by the European Union’s Horizon 2020 research and innovation program under grant agreement No 965381; NIMH grants U01AR076092-01A1, 1R21MH1264940, R01MH116037; 1R01NS128535 – 01; Oregon Health and Science University, Otsuka Pharmaceuticals, Noven Pharmaceuticals Incorporated, and Supernus Pharmaceutical Company.

The objective is to investigate the presentation, complications, management, and outcomes of copper deficiency-induced neurological pathologies due to Wilson disease (WD) overtreatment. We examined the case of a WD patient who developed a low thoracic dorsal myelopathy due to chronic hypocupremia from excessive zinc therapy. A comprehensive literature review was conducted to identify similar cases. Ten additional cases of neurological pathology resulting from copper deficiency in the context of WD over-treatment were identified, all occurring during therapy with zinc salts. Myelopathy and peripheral neuropathy were the most common complications, while two additional groups reported leukoencephalopathy. Early cytopenia was often associated with copper deficiency-related neurological pathology appearing early in the context of copper deficiency. WD patients undergoing treatment, especially with zinc salts, should be closely monitored to prevent over-treatment and the consequent copper deficiency. Regular complete blood counts could provide early detection of copper deficiency, avoiding irreversible neurological damage. Swift recognition of new neurological signs not consistent with WD and timely discontinuation of the decoppering therapy are critical for improving outcomes. The optimal management, including the potential benefit of copper supplementation in patients with WD and subsequent therapy adjustments, remains unclear and necessitates further investigation. Despite the general poor functional neurological outcomes, there were some exceptions that warrant further exploration., (© 2023. The Author(s).)

Psychosocial interventions remain the primary strategy for addressing cocaine use disorder (CUD), although many individuals do not benefit from these approaches. Amphetamine-based interventions have shown significant promise and may improve outcomes among individuals continuing to use cocaine in the context of behavioral interventions. One hundred forty-five adults (122 males) who used cocaine a minimum of 4 days in the prior month and met the criteria for a CUD enrolled in a two-stage intervention. All participants received a computer-delivered skills intervention and contingency management for reinforcing abstinence for a 1-month period. Participants demonstrating less than 3 weeks of abstinence in the first month were randomized to receive mixed amphetamine salts-extended release (MAS-ER) or placebo (80 mg/day) for 10 weeks under double-blind conditions. All participants continued with the behavioral intervention. The primary outcome was the proportion of individuals who achieved 3 consecutive weeks of abstinence as measured by urine toxicology confirmed self-report at the study end. The proportion of participants demonstrating 3 consecutive weeks of abstinence at study end did not differ between the medication groups: MAS-ER = 15.6% (7/45) and placebo = 12.2% (5/41). Participants who received MAS-ER reported greater reductions in the magnitude of wanting cocaine, although no group differences were noted in either the perceived improvement or the frequency of wanting cocaine. Retention rates were greater for both medication groups compared to behavioral responders. Overall, augmenting a behavioral intervention with MAS-ER did not significantly increase the abstinence rate among individuals continuing to use cocaine following a month of behavioral therapy alone. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain., Methods: This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium., Results: Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p  = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p  = 0.008)., Conclusions: This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Purpose: Immediate-release forms of generic mixed amphetamine salts (MAS) have been the subject of passive surveillance reports signaling lack of effectiveness. We examined switching patterns that might suggest whether long-term users of specific MAS are more likely to switch away or switch back after use of the MAS of interest in the FDA's Sentinel Distributed Database., Methods: We required at least 60-day continuous supply of selected MAS grouped by Abbreviated New Drug Application (ANDA) to describe patterns of switching away from and to generics approved under the ANDAs of interest among individuals ages 15-64 years with attention deficit hyperactivity disorder or narcolepsy during 2013-2019., Results: We observed the greatest number of treatment episodes for ANDA 040422 (n = 525 771), followed by ANDA 202424 (n = 181 693), ANDA 040439 (n = 62 363), ANDA 040440 (n = 21 143), and ANDA 040480 (n = 8792). Of those with switches away from their original ANDA, episodes initiated on generic products under ANDA 040422 (48.6%) and ANDA 202424 (43.0%) were most likely to switch back, while those initiated on generic product under ANDA 040480 were least likely (24.1%). Of those episodes with switches to a generic under an ANDA of interest, about one-third (range 27.1% to 37.0%) switched back to the same product. These switches back had a median time to switch of about 30 days., Conclusions: These descriptive analyses, although subject to limitations, did not suggest increased switching away or switching back after use of the generics of interest. Continued post-marketing surveillance is warranted., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Context: Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts., Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events., Data Sources: A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency., Data Extraction: Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated., Data Analysis: Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children., Conclusion: Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations., Prospero Registration No: CRD42020196984., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BD) are often comorbid in patients and can have significant overlap in symptoms. Because of this common comorbidity and often overlapping symptoms, accurate diagnoses can be difficult. The standard treatment for these comorbid disorders is a mood stabilizer with the possibility of adding a psychostimulant. However, research suggesting treatment for comorbid disorders with a psychostimulant without a mood stabilizer is lacking. Here, we present two cases where mixed amphetamine salts, which are traditionally avoided in those with BD, were effectively used without a mood stabilizer to treat comorbid BD and ADHD in both patients. The outcome of this case series serves to motivate future investigations which are needed to validate treatment with a psychostimulant without a mood stabilizer for the treatment of comorbid BD and ADHD., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Aim: This systematic review and meta-analysis evaluated whether the home use of mouthwashes containing potassium salts is effective in reducing and controlling dentin hypersensitivity (DH)., Methods and Materials: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and was registered in PROSPERO (CRD42021228410). Randomized clinical trials evaluating the use of mouthwashes containing potassium salt for daily household mouthwash for at least four weeks to reduce DH compared with a control mouthwash were selected, with no limitation on year of publication. Electronic research was carried out in PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library by two independent researchers. One hundred thirty-three articles were obtained, and nine were selected according to the inclusion criteria., Results: The selected studies evaluated DH through tests of sensitivity to tactile and evaporative stimuli and showed that, for the tactile stimulus, there were no baseline differences between groups (p=0.12; mean difference: -0.33; confidence intervals [CI]: -0.73 to 0.08). However, there were significant differences after two weeks of use (p=0.00001; mean difference: 4.67; CI: 4.53 to 4.81), after four weeks (p=0.00001; mean difference: 13.29; CI: 13.03 to 13.55), and after eight weeks (p=0.00001; mean difference: 8.88; CI: 5.73 to 12.02) favoring the experimental group. The results of the evaporative test showed no differences in the baseline assessment between the two groups (p=0.50; mean difference: -0.02; CI: -0.09 to 0.04), but after four weeks (p=0.00001; mean difference: -0.32; CI: -0.44 to -0.20), and eight weeks of use (p=0.00001; mean difference: -0.42; CI: -0.57 to -0.27) there were differences favoring the experimental group. The incidence of side effects showed no differences between the two groups (p=0.89; mean difference: 1.03; CI: 0.67 to 1.58)., Conclusion: The daily use of mouthwashes containing potassium salt is effective in the treatment of dentinal hypersensitivity, as a complementary step to brushing at least twice a day for two weeks, four weeks, and up to eight weeks, without presenting side effects., (© Operative Dentistry, 2023.)

After over 50 years of use, lithium-salts remain the first-line therapy for the management of bipolar disorder. Throughout this period, the potential for lithium salts has been extensively studied and numerous data favor its use in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD). We reviewed existing evidence gathered from clinical case reports and studies on the effect of lithium on neuropsychological symptoms of AD and as a disease-modifying treatment acting on cognitive symptoms. The review summarizes the molecular pathways, involving GSK-3β inhibition and neuroprotection, through which lithium is proposed to exert its effect. Limitations to its current use in AD are discussed and future perspectives as a potential treatment option for AD are considered in regard to ongoing clinical trials using different forms of lithium.

Hypoparathyroidism remains the single endocrine deficiency disease that is not habitually treated with the missing hormone. In this article, we aim to provide a review of the conventional approach and the novel therapies as well as an overview of the perspectives on the treatment of this rare condition. We conducted a literature review on the conventional therapy using vitamin D analogs and calcium salts, indications for thiazide diuretics and phosphorus binders, PTH analogs history and usage, and the drugs that are currently being tested in clinical trials. Conventional treatment involves calcium salts and vitamin D analogs. Thiazide diuretics can be used to reduce hypercalciuria in some cases. A low-phosphate diet is recommended, and phosphate binders are rarely needed. During pregnancy, a careful approach is necessary. The use of PTH analogs is a new approach despite the limitation of high cost. Studies have included modified PTH molecules, calcilytics, microencapsulation of human parathyroid cells, and allotransplantation.

Calcinosis cutis is defined as abnormal deposition of calcium salts in the skin and subcutaneous tissues. Dystrophic calcification, the most common form of calcinosis cutis, is associated with autoimmune connective tissue diseases. This condition is associated with severe pain and can affect the patient's quality of life and lead to long-term disability. Treatment is often challenging, and there is a very limited evidence base for potential treatments of calcinosis cutis associated with systemic sclerosis and dermatomyositis. Inkless tattoo is very similar to microneedling, a minimally invasive procedure stimulating the wound-healing cascade contributing to elastin and collagen formation as well as neovascularization. This technique has not been reported as a potential therapeutic option for calcinosis cutis. Here, we present a patient with calcinosis cutis in the setting of dermatomyositis that responded dramatically to inkless tattoo application. Our results support the need for future studies of microneedling in patients with this disorder., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Lithium salts are widely used clinically, mainly for treatment of bipolar disorder, in which it is highly effective. Various preparations have been developed and tested, including older immediate-release (IR) forms of lithium carbonate and other salts and formulations with slow-release (SR) properties, developed in hopes of increasing the tolerability of lithium treatment, adherence to its use, and possibly its efficacy. Systematic reviews of head-to-head comparisons of pharmacological and clinical properties of such preparations are lacking. Accordingly, we systematically reviewed clinical studies of both IR and SR formulations of lithium salts, seeking to compare their pharmacokinetic properties, adverse effects, clinical tolerability, and clinical effectiveness. Very few such comparative studies were identified and they are highly heterogeneous in design and findings. In 11 included reports, SR formulations appeared to be better tolerated and possibly to be associated with greater adherence to treatment. Studies of comparative clinical efficacy are lacking. Despite decades of use of various lithium salts, systematic comparisons of the pharmacological and clinical properties of IR vs. SR preparations remain rare and to be deepened, though with suggestive superiority of SR salts.

Diet therapy for hyperkalemia in chronic kidney disease (CKD) is at a crossroads: many researchers and clinicians are no longer recommending the low-potassium diet, which has defined practice for the last half century, and instead are favoring a high-potassium, plant-rich diet. Central to this shift is the observation that reported dietary potassium intake is not associated with plasma potassium concentrations. However, kinetic studies using potassium salts indicate that people with CKD have impaired potassium tolerance that may make them susceptible to transient increases in plasma potassium levels from dietary potassium (postprandial hyperkalemia). Observational studies generally measure plasma potassium in the fasting state and before hemodialysis treatment, and therefore may not detect the acute effects of dietary potassium on plasma potassium concentrations. Differences between the acute and chronic effects of dietary potassium on plasma potassium levels may help explain clinical experiences and case studies attributing hyperkalemic episodes in patients with CKD to intakes of high-potassium foods despite their apparent lack of association. To reconcile these findings, an etiology-based approach to managing hyperkalemia is proposed in this review. The approach combines key elements of the low-potassium and plant-rich diets, and adds new features of meal planning to lower the risk of postprandial hyperkalemia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite being a promising strategy, current chemotherapy for gastric cancer (GC) is limited due to adverse side effects and poor survival rates. Therefore, new drug-delivery platforms with good biocompatibility are needed. Recent studies have shown that nanoparticle-based drug delivery can be safe, eco-friendly, and nontoxic making them attractive candidates. Here, we develop a novel selenium-nanoparticle based drug-delivery agent for cancer treatment from plant extracts and selenium salts., Results: Selenium cations were reduced to selenium nanoparticles using Kaempferia parviflora (black ginger) root extract and named KP-SeNP. Transmission electron microscopy, selected area electron diffraction, X-ray diffraction, energy dispersive X-ray, dynamic light scattering, and Fourier-transform infrared spectrum were utilized to confirm the physicochemical features of the nanoparticles. The KP-SeNPs showed significant cytotoxicity in human gastric adenocarcinoma cell (AGS cells) but not in normal cells. We determined that the intracellular signaling pathway mechanisms associated with the anticancer effects of KP-SeNPs involve the upregulation of intrinsic apoptotic signaling markers, such as B-cell lymphoma 2, Bcl-associated X protein, and caspase 3 in AGS cells. KP-SeNPs also caused autophagy of AGS by increasing the autophagic flux-marker protein, LC3B-II, whilst inhibiting autophagic cargo protein, p62. Additionally, phosphorylation of PI3K/Akt/mTOR pathway markers and downstream targets was decreased in KP-SeNP-treated AGS cells. AGS-cell xenograft model results further validated our in vitro findings, showing that KP-SeNPs are biologically safe and exert anticancer effects via autophagy and apoptosis., Conclusions: These results show that KP-SeNPs treatment of AGS cells induces apoptosis and autophagic cell death through the PI3K/Akt/mTOR pathway, suppressing GC progression. Thus, our research strongly suggests that KP-SeNPs could act as a novel potential therapeutic agent for GC., (© 2022. The Author(s).)

Lithium-salts stand on the first line of therapy for the management of specific psychiatric conditions, mainly bipolar mood disorder. It is also known to protect the brain against neurodegenerative processes such as Alzheimer's disease. Despite the mentioned merits, recent studies have revealed that high dose or prolonged lithium intake deteriorate the function of multiple key organs including heart, ovaries, thyroid gland and kidneys. Mechanistically, both positive and negative effects of lithium are mediated through methylation of β-catenin nuclear-binding proteins which is potentiated by lithium-induced inhibition of GSK-3 or inositol monophosphatase. The current study briefly reviews the recent experimental data on lithium therapy considering both positive (i.e., neuroprotective) and negative aspects. In this regard, the question is that whether doses of lithium administered in experimental research are comparable with the therapeutic doses, as currently prescribed in clinical practice. It should be noted that the experimental data on animal studies, as widely reviewed here, could not be directly generalized to clinic. This is mainly because lithium doses applied in animal models are usually higher than therapeutic doses, however, there are evidence indicating that even animal to human translated doses of lithium, cause serious complications and this has been reported by meta-analyses on human studies. Therefore, we suggest the clinicians to use lithium-salts with precaution particularly in pregnancy and precisely adjust lithium concentration considering the patient's general health status to avoid lithium toxicity. Indeed, alternative approaches are recommended when the subject is pregnant, prolonged therapy is required or specific organ dysfunction is diagnosed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Well established and common practice in conservative management of omphalocele major is escharotics therapy with different topical agents. Among them mercurochrome, alcohol, silver salts, povidone iodine, acacia nilotca paste are commonly used. It is a comparative study between application of acacia nilotica paste and povidone iodine solution as a primary non surgical treatment of omphalocele major regarding efficacy and safety of these two topical agents. A double blind randomized controlled study was conducted at the department of Paediatric Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2016 to June 2019. In this study 20 cases of omphalocele major and randomly divided into two equal groups. Group A and Group B treated with acacia nilotica paste and povidone iodine solution respectively. Gastroschisis, ruptured-omphalocele major or omphalocele minor excluded in this study. The size of the fascial defect in cm, time required for full oral feeding tolerance and duration of hospital stay were evaluating parameters. Patients with Group A tolerated full oral feeding earlier, shorter total hospital stay duration and low mortality rate than those from Group B. Application of acacia nilotica is a safe and effective treatment of omphalocele major regarding rapid full oral feeding tolerance, shorter hospital stay and low mortality rate.

Nonpharmacological treatment is still an important supplement to the pharmacological treatment of hypertension. Thereby, either an elevated blood pressure can be lowered further or, alternatively, the use of antihypertensive drugs can be reduced. In the context of nonpharmacological treatment of hypertension, sodium restriction plays an important role. Sodium intake can either be reduced by lowering excessive dietary salt consumption or by the use of table salts with reduced sodium content. Lower dietary sodium consumption lowers blood pressure. This was controversial for a long time; however, now more and more observational and interventional studies have confirmed this fact. Nevertheless, some studies have shown an association of low salt consumption with increased mortality. This observation is explained by the so-called reverse epidemiology. This means that diseases with increased mortality, such as consuming diseases or severe heart diseases are associated with lowered food intake and as a consequence, with lower sodium intake. In addition to sodium restriction, the use of so-called salt substitutes with lower sodium content is also effective in lowering blood pressure. In most of the salt substitutes examined so far sodium chloride is partly replaced by potassium chloride. Numerous investigations show that these salt substitutes lower blood pressure. From a statistical point of view side effects such as hyperkalemia are very rare; however, hyperkalemia is potentially life-threatening. Therefore, the broader use of these salt substitutes is principally helpful but these salts should only be used after medical consultation. Especially renal insufficiency and the use of certain drugs, such as potassium-sparing diuretics and blockers of the renin-angiotensin system increase the risk of hyperkalemia., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, being fatal if untreated. In search of a more effective treatment for VL, one of the main strategies is the development and screening of new antileishmanial compounds. Here, we reported the synthesis of seven new acetyl functionalized 1,2,3-triazolium salts, together with four 1,2,3-triazole precursors, and investigated their effect against different strains of L. infantum from dogs and humans. The 1,2,3-triazolium salts exhibited better activity than the 1,2,3-triazole derivatives with IC 50 range from 0.12 to 8.66 μM and, among them, compound 5 showed significant activity against promastigotes (IC 50 from 4.55 to 5.28 μM) and intracellular amastigotes (IC 50 from 5.36 to 7.92 μM), with the best selective index (SI ~ 6-9) and reduced toxicity. Our findings, using biochemical and ultrastructural approaches, demonstrated that compound 5 targets the mitochondrion of L. infantum promastigotes, leading to the formation of reactive oxygen species (ROS), increase of the mitochondrial membrane potential, and mitochondrial alteration. Moreover, quantitative transmission electron microscopy (TEM) revealed that compound 5 induces the reduction of promastigote size and cytoplasmic vacuolization. Interestingly, the effect of compound 5 was not associated with apoptosis or necrosis of the parasites but, instead, seems to be mediated through a pathway involving autophagy, with a clear detection of autophagic vacuoles in the cytoplasm by using both a fluorescent marker and TEM. As for the in vivo studies, compound 5 showed activity in a mouse model of VL at 20 mg/kg, reducing the parasite load in both spleen and liver (59.80% and 26.88%, respectively). Finally, this compound did not induce hepatoxicity or nephrotoxicity and was able to normalize the altered biochemical parameters in the infected mice. Thus, our findings support the use of 1,2,3-triazolium salts as potential agents against visceral leishmaniasis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Methylphenidate (MPH) and mixed D,L-amphetamine salts (MASs; Adderall) were previously found to have unreliable effects on judgment and decision processes., Objective: We predicted that MPH and MASs have a specific effect of reducing heuristic responses, which should lead to increased performance on the cognitive reflection test (CRT). The CRT is considered to be a testbed for heuristic versus deliberative response modes., Methods: We recruited a sample of 15,361 individuals using the Prolific Academic crowdsourcing platform. From this initial pool, our final sample consisted of 294 participants (125 MPH users and 169 MASs users) who conformed to the study criteria and completed the experimental tasks. Tasks were performed on days where participants were either medicated or not, allowing to assess the effect of medication status., Results: There was a strong positive effect of taking MPH on CRT scores (Cohen's d = 0.40) which was not qualified by frequency of MPH usage, ADHD symptoms, and demographic factors. There was also a somewhat weaker effect for MASs (Cohen's d = 0.07). No effects of MPH and MASs were recorded for risk-taking and numeracy., Conclusions: The results indicate that MPH enhances decision-making in tasks where heuristic responses typically bias it., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Iron deficiency is one of the most common nutritional deficiencies worldwide and is often treated with oral iron supplements. However, commonly used supplements, including those based on ferrous iron salts, are associated with gastrointestinal side effects and unfavorable changes in the intestinal microbiome. Sucrosomial® iron is a novel iron formulation that is effective at treating iron deficiency, and with fewer gastrointestinal side effects, yet its effect on the gut microbiome has not been examined previously. Thus, we treated mice for two weeks with diets containing either Sucrosomial® iron or ferrous sulfate as the sole iron source and examined bacterial communities in the intestine using 16S Microbial Profiling of DNA extracted from feces collected both prior to and following dietary treatment. Mice treated with Sucrosomial® iron showed an increase in Shannon diversity over the course of the study. This was associated with a decrease in the abundance of the phylum Proteobacteria, which contains many pathogenic species, and an increase in short chain fatty acid producing bacteria such as Lachnospiraceae, Oscillibacter and Faecalibaculum. None of these changes were observed in mice treated with ferrous sulfate. These results suggest that Sucrosomial® iron may have a beneficial effect on the intestinal microbiome when compared to ferrous sulfate and that this form of iron is a promising alternative to ferrous iron salts for the treatment of iron deficiency., (© 2021. The Author(s).)

Objective: Assess executive function (EF) improvement with SHP465 mixed amphetamine salts (MAS) extended-release in adults with attention-deficit/hyperactivity disorder (ADHD) using responder analyses of the Brown Attention-Deficit Disorder Scale (BADDS)., Methods: Post hoc analyses examined data from placebo-controlled SHP465 MAS dose-optimization (12.5-75 mg) and fixed-dose (25-75 mg) studies. Treatment response was assessed using two definitions (BADDS total score at endpoint <50 [no EF impairment] vs. ≥50 [impaired]; BADDS total score at endpoint relative to the in-treatment 90% CI range for baseline total score [below the range = improved])., Results: Response rates (SHP465 MAS vs. placebo) favored SHP465 MAS (all nominal p < .0001) in the dose-optimization (BADDS <50: 41.9% vs. 19.2%; below 90% CI range: 57.4% vs. 29.6%) and fixed-dose (BADDS <50: 51.9% vs. 16.7%; below 90% CI range: 70.6% vs. 32.3%) studies., Conclusion: Improvement in EF measured by BADDS response rates was approximately 2-fold greater with SHP465 MAS than placebo.

Background: Bismuth oxychloride produced by interaction of bismuth compounds with gastric acid is believed to damage Helicobacter pylori. The effect of bismuth salts on H. pylori in the presence of strong acid suppression is unknown. This randomized trial aimed to determine effects of bismuth subcitrate on H. pylori with and without acid suppression., Methods: H. pylori -positive participants were allocated (1:1:1) to receive (a) no treatment (control), (b) colloidal bismuth subcitrate (CBS, 125 mg/tab), or (c) CBS plus high-dose proton-pump inhibitor (PPI), esomeprazole 40 mg q.i.d. for 3 days. In the treatment groups, CBS was given: 1 dose, 1 hour before endoscopy, 1 dose, 4 hours before endoscopy, or q.i.d. 24 hours before endoscopy. The study end-points were evaluated using transmission electron microscopy to observe the morphological changes of H. pylori in antral and corpus biopsies., Results: Twenty-seven H. pylori carriers were enrolled in this trial with qualitative end-points. In the no treatment group, active budding and replication of H. pylori were observed. In the CBS group, cellular swelling, vacuolization, structural degradation, and cell wall eruption of H. pylori were observed, with no apparent association with when the CBS was given. Among those receiving high-dose PPI-plus CBS or CBS only, there were no differences in number of H. pylori present or severity of bacterial damage whether CBS was given 1, 4, or 24 hours before endoscopy., Conclusions: Based on direct morphological evaluation, the toxic effect of CBS treatment on H. pylori was demonstrated independent of acid suppression with PPI., (© 2021 John Wiley & Sons Ltd.)

Objectives: In a previous pivotal study of children and adolescents (aged 6-17 years) with attention-deficit/hyperactivity disorder (ADHD), dose-optimized SHP465 mixed amphetamine salts (MAS) extended-release (12.5-25 mg once daily) was superior to placebo in reducing ADHD symptoms. This study evaluated the efficacy, tolerability, and safety of 6.25 mg SHP465 MAS once daily (one-half the lowest approved dose for adolescents and adults) versus placebo in children aged 6-12 years with ADHD. Methods: Children (aged 6-12 years) with Diagnostic and Statistical Manual of Mental Disorders, Fifth edition-defined ADHD; baseline ADHD-Rating Scale, Fifth Edition, Child, Home Version total scores (ADHD-RS-5-HV-TS) ≥28; and baseline Clinical Global Impressions-Severity scores ≥4 were eligible. Participants received 6.25 mg SHP465 MAS once daily or placebo for 4 weeks. The primary (ADHD-RS-5-HV-TS change from baseline at week 4) and key secondary (Clinical Global Impressions-Improvement [CGI-I] score at week 4) efficacy end points were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes. Results: Of 89 randomized participants, 83 completed the study (placebo, n  = 41; SHP465 MAS, n  = 42). At week 4, the least squares mean (95% confidence interval) treatment differences (SHP465 MAS-placebo) were not statistically significant for ADHD-RS-5-HV-TS change (-1.9 [-6.8 to 3.1], p  = 0.451; effect size [ES] = 0.17) or CGI-I score (-0.1 [-0.5 to 0.3], nominal p  = 0.597; ES = 0.12). The percentage of participants reporting TEAEs was 16.3% with placebo and 24.4% with SHP465 MAS. The most frequently reported TEAEs (placebo; SHP465 MAS) were headache (7.0%; 4.4%) and decreased appetite (4.7%; 2.2%). Minimal increases in blood pressure were observed with SHP465 MAS at the final on-treatment assessment. Conclusions: SHP465 MAS 6.25 mg once daily (one-half the lowest dose approved for adolescents and adults) was well tolerated in children aged 6-12 years but was not superior to placebo in reducing ADHD symptoms, suggesting that this dose of SHP465 MAS was subtherapeutic in this age group. The Clinical Trial Registration number: NCT03325881.

Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by 23 Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown.

Background: Many medications are formulated with acid salts. Their effect on acid-base balance in CKD is unclear., Methods: We calculated the acid load (meq/d) from medications prescribed to 74 United States veterans with diabetes and CKD to identify agents with high potential acid load. We also determined cross-sectional associations between the acid load from medications and acid-base parameters after adjusting for demographics, eGFR, protein intake, and other confounders., Results: Of the 125 medications prescribed, 31 (25%) contained an acid salt. Metformin hydrochloride (15.4 meq/d at 2550 mg/d) and gabapentin hydrochloride (13.0 meq/d at 2700 mg/d) were identified as agents with a high potential acid load. Mean daily acid load from medications was 6.6 meq/d in the overall cohort, 14.2 meq/d in the high medication acid load group (≥7.7 meq/d, n =29), and 1.6 meq/d in the low medication acid load group (<7.7 meq/d, n =45). After adjusting for potential confounders, those in the high acid load group had 1.7 meq/L lower total carbon dioxide (CO 2 ) and 2.2 meq/L higher anion gap than those in the low acid load group. Use of gabapentin alone was not associated with differences in total CO 2 or anion gap. Use of metformin alone was associated with 0.7 meq/L lower total CO 2 and 1.0 meq/L higher anion gap. Use of metformin with gabapentin was associated with 1.8 meq/L lower total CO 2 and 2.4 meq/L higher anion gap. The higher anion gap was not explained by higher serum lactate levels. The acid load from medications was not associated with differences in urinary ammonium, titratable acid, or pH., Conclusions: Medications containing acid salts, particularly metformin hydrochloride and gabapentin hydrochloride, are sources of an exogenous acid load. These agents may influence serum total CO 2 levels and serum anion gap in individuals with CKD., Clinical Trial Registry Name and Registration Number: Investigations of the Optimum Serum Bicarbonate Level in Renal Disease, NCT01574157., Competing Interests: K. Raphael received a one-time consulting fee from Tricida, Inc. in October 2016. J. Gardner and K. Tuttle have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Objective: Evaluate the efficacy and tolerability of triple-bead mixed amphetamine salts (MAS) in ADHD. Method: Adults with ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥32 were randomized to 6 weeks of triple-bead MAS (25, 50, or 75 mg) or placebo. The primary endpoint was ADHD-RS-IV total score change from baseline at end of study (EOS). Results: Least squares mean (95% confidence interval [CI]) treatment differences for ADHD-RS-IV total score changes from baseline to EOS significantly favored triple-bead MAS (all doses combined: -10.6 [-13.2, -8.0]; p < .0001); there were no significant differences between triple-bead MAS dosages. The most frequently reported TEAEs with triple-bead MAS (all doses combined) included insomnia, decreased appetite, and dry mouth. Mean ± SD pulse and systolic blood pressure increases at EOS were 3.5 ± 10.33 bpm and 0.3 ± 10.48 mmHg with triple-bead MAS (all doses combined). Conclusion: Triple-bead MAS significantly reduced adult ADHD symptoms; the safety profile was consistent with previous triple-bead MAS studies.

Objective: The aim of this study was to evaluate the long-term safety of triple-bead mixed amphetamine salts (MAS) in adults with ADHD. Method: Adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR ) ADHD criteria and satisfying study criteria from one of two antecedent studies were enrolled in this 52-week (dose titration, 4 weeks; dose maintenance, 11 months) open-label extension. The protocol included 12.5- to 75-mg triple-bead MAS but was amended to a maximum of 50-mg triple-bead MAS. Safety evaluations included treatment-emergent adverse events (TEAEs) and vital signs. Clinical outcome measures included ADHD Rating Scale-IV (ADHD-RS-IV) total score changes. Results: Of 505 enrolled participants, 266 completed the study; the M ± SD daily dose during the study was 48.0 ± 15.96 mg. The most frequent TEAEs were insomnia (initial insomnia, insomnia, early morning awakening, middle insomnia; 38.2%), headache (25.7%), and dry mouth (20.2%). Study discontinuations were more frequent with higher doses of triple-bead MAS (37.5-75 mg) than with lower doses (12.5 and 25 mg). Blood pressure and pulse increases were observed at end-of-study. Mean ADHD-RS-IV total score decreases from antecedent study and open-label baselines at end-of-study were -23.3 ± 11.44 and -7.9 ± 13.19, respectively. Conclusion: Triple-bead MAS exhibited a long-term safety profile comparable with previous reports and demonstrated evidence of continued symptom control for up to 12 months.

Background: Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users., Methods: A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report., Results: The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%)., Conclusions: While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept.", (Copyright © 2019 Elsevier B.V. All rights reserved.)

The polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women in reproductive age with the so far undetermined causes of development. In the etiopathogenesis of PCOS, the role of insulin resistance is emphasised, which was an indication for the attempts at using chromium III salts (Cr) in augmenting pharmacotherapy applied in patients. The analysis of the usefulness and efficacy of this approach was the direct goal of this thesis. Animal tests confirmed the efficacy of chromium in maintaining the appropriate level of glycaemia and insulinaemia, normalisation of plasma concentrations of microelements and also a correlation between the Cr level, insulin and dehydroepiandrosterone (DHEA) was found. A decrease in the expression of 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase was identified in adipose tissue. Clinical studies, although sparse, show that the supplementation with chromium can improve BMI and the parameters evaluating the control of glycaemia and increase the chances for ovulation and regular menstruation. However, the small number and a variability in study protocols makes comparing them very difficult. A completely new subject that has not been yet studied is the possibility of using chromium in levelling mood disorders in patients with PCOS. Currently, there are still no sufficient proofs for introducing chromium as a standard in treating and preventing insulin resistance in patients with PCOS. However, this direction remains open, and treating insulin resistance is an important challenge in clinical practice.

Objective: Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). The presence of sleep problems at the time of presentation for ADHD treatment could impact the level of improvement in ADHD symptoms or executive function occurring with ADHD pharmacotherapy. Therefore, we examined the influence of baseline sleep quality on the effects of SHP465 mixed amphetamine salts (MAS) extended-release., Methods: Adults (18-55 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥ 24 were randomized to once-daily SHP465 MAS (12.5-75 mg) or placebo in a 7-week, double-blind, dose-optimization study. Post-hoc analyses evaluated SHP465 MAS treatment effects on ADHD symptoms, using the ADHD-RS-IV, and executive function, using the Brown Attention-Deficit Disorder Scale (BADDS), based on baseline sleep quality as defined by Pittsburgh Sleep Quality Index (PSQI) scores [sleep quality impaired (PSQI total score > 5; PSQI component scores 2 or 3) versus not impaired (PSQI total score ≤ 5; PSQI component scores 0 or 1)]. Analyses were conducted in the intent-to-treat population., Results: Of 280 enrolled participants, 272 were randomized (placebo, n = 135; SHP465 MAS, n = 137). The intent-to-treat population consisted of 268 participants (placebo, n = 132; SHP465 MAS, n = 136), and 170 participants (placebo, n = 76; SHP465 MAS, n = 94) completed the study. Treatment differences nominally favored SHP465 MAS over placebo in both sleep impairment groups regarding ADHD-RS-IV total score changes (all nominal p < 0.05), except for those with impairment defined by sleep efficiency (p = 0.2696), and regarding BADDS total score changes (all nominal p < 0.05), except for those with impairment defined by sleep duration (p = 0.1332) and sleep efficiency (p = 0.8226). There were no statistically significant differences in SHP465 MAS treatment effects between sleep impairment groups., Conclusions: Improvements in ADHD symptoms and executive function occurred with dose-optimized SHP465 MAS, regardless of baseline impairment in some aspects of sleep in adults with ADHD, with no significant differences observed as a function of sleep impairment., Clinical Trials Registration: ClinicalTrials.gov identifier-NCT00150579.

Objective: To observe the damage of various organs of rats with exertional heatstroke (EHS), and to investigate the protective effect of oral rehydration salts III (ORS III) on multi-organ function in rats with EHS., Methods: Fifty-one male Sprague-Dawley (SD) rats were randomly divided into four groups by random digit table: normal control group (n = 13), EHS group (n = 13), EHS+water group (n = 12), and EHS+ORS III group (n = 13). All rats in the EHS groups received adaptive training for 7 days before the experiment. On the 8th day, the rats of EHS+water and EHS+ORS III groups were orally given 20 mL/kg water or ORS III 30 minutes before the experiment. No pretreatment was performed in the EHS group. EHS model was reproduced by forcing rats to run under hot environment. The rats which refused to exercise and which core temperature > 40.5 centigrade were considered as the onset of EHS. The rats in the normal control group were exposed to room temperature (25±2) centigrade and humidity (50±5)% without any treatment. Six hours later, blood of inferior vena cava was collected, and the levels of serum MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (SCr), blood urea nitrogen (BUN), serum potassium, serum sodium and serum chloride were determined by automatic chemical analyzer. Serum intestinal fatty acid-binding protein (I-FABP) was determined by enzyme linked immunosorbent assay (ELISA)., Results: The levels of LDH, ALT, AST, BUN, serum sodium and serum chloride in the EHS group were significantly higher than those in the normal control group [LDH (U/L): 1 220±427 vs. 837±485, ALT (U/L): 138 (97, 164) vs. 37 (33, 42), AST (U/L): 409 (380, 566) vs. 86 (78, 104), BUN (mmol/L): 11.7 (9.6, 13.2) vs. 5.9 (5.5, 6.1), serum sodium (mmol/L): 148.0 (143.5, 154.5) vs. 139.0 (138.0, 140.5), serum chloride (mmol/L): 100.9±2.3 vs. 97.3±1.4, all P < 0.05], but no significant difference in CK-MB, SCr or serum potassium could be found [CK-MB (U/L): 1 280±373 vs. 1 379±480, SCr (μmol/L): 38.2±7.5 vs. 35.5±6.3, serum potassium (mmol/L): 5.5 (4.4, 6.2) vs. 4.7 (4.4, 4.9), all P > 0.05]. In the EHS+ORS III group, only serum potassium level was significantly lower than that in the EHS group [mmol/L: 4.0 (3.7, 4.4) vs. 5.5 (4.4, 6.2), P < 0.01], while no significant difference in other parameters was found between the EHS+ORS III group and the EHS group as well as the EHS+water group. Serum I-FABP level in the EHS group was significantly higher than that in the normal control group [μg/L: 36.90 (29.10, 45.00) vs. 11.39 (0.31, 20.80), P < 0.01]. Serum I-FABP level in the EHS+water and EHS+ORS III groups were notably lower than that in the EHS group [μg/L: 24.19 (20.00, 28.36), 0.31 (0.31, 5.58) vs. 36.90 (29.10, 45.00), both P < 0.01], additionally, I-FABP level was much lower in the EHS+ORS III group (P < 0.01)., Conclusions: EHS could lead to liver, intestinal barrier dysfunction and electrolyte disturbance. Pre-treatment of ORS III could alleviate the intestinal dysfunction and electrolyte disorder caused by EHS in rats. It can lower the serum potassium to some extent. However, ORS III failed to protect liver from EHS.

Objective: Psychostimulants are the first-line treatment in adults with attention-deficit hyperactivity disorder (ADHD). This meta-analysis aimed to evaluate the efficacy, acceptability, and tolerability of lisdexamfetamine (LDX), mixed amphetamine salts (MASs), modafinil (MDF), and methylphenidate (MPH) in comparison with placebo., Data Sources: We systematically searched PubMed/MEDLINE and Clinicaltrials.gov in May 2016, along with CENTRAL and EU Clinical Trials Register in February 2016, for the randomized, double-blind, placebo-controlled, parallel-group clinical trials conducted on adults diagnosed with ADHD., Study Selection and Data Extraction: Substantial comorbidity, substance abuse or dependence, and nonpharmacological interventions represented grounds for exclusion. Published reports were the sole source for data extraction. Improvement in ADHD symptoms was the primary outcome. Random-effects model meta-analysis was applied to calculate the standardized mean difference (SMD) with 95% CIs., Data Synthesis: The search retrieved 701 records, of which 20 studies were eligible for analysis. High effect size (expressed as SMD) in reducing ADHD symptoms was observed for LDX (-0.89; 95% CI = -1.09, -0.70), whereas MASs (-0.64; 95% CI = -0.83, -0.45) and MPH (-0.50; 95% CI = -0.58, -0.41) reduced symptoms moderately compared with placebo. No efficacy was shown for MDF (0.08; 95% CI; -0.18, 0.34). Relevance to Patient Care and Clinical Practice: In this meta-analysis, the efficacy, tolerability, and acceptability of psychostimulants were compared with that for placebo. Five of the included trials have not been evaluated in any of the previously published meta-analyses., Conclusions: The results suggest that LDX has the largest effect size and has a promising potential for treating adults with ADHD.

Objective: To assess the efficacy of oral rehydration salts in children with neurally mediated syncope of different hemodynamic types., Methods: Children with unexplained syncope or pre-syncope who visited or were hospitalized between March 2012 and February 2015 were enrolled in the study. Checked by the head-up tilt test, 105 children (aged 4-18 years, with a mean age of 11.96 ± 2.86 years) were diagnosed with neurally mediated syncope. Of them, 73 had vasovagal syncope (vasodepressor type in 46, mixed/cardioinhibitory types in 27), and 32 had postural orthostatic tachycardia syndrome. They were randomized into the oral rehydration salts plus health education group (n = 55) and the health education alone group (n = 50). All treated children were followed up. The follow-up time ranged from 6 to 25 (14.82 ± 6.13) months. Short-term effects were assessed according to the recurrence of clinical symptoms and reviews of head-up tilt test results 6 months after drug withdrawal. Long-term effects were compared between both groups of children with neurally mediated syncope., Results: Short-term effect: No significant differences were found in subjective response rate and head-up tilt test negative results rate among different hemodynamic types ( P > .05). Long-term effect: Compared with the health education alone group, the cumulative response rate increased after treatment with oral rehydration salts ( P < .05). Among oral rehydration salts-treated children, the cumulative response rate was higher in those with vasodepressor vasovagal syncope than with mixed/cardioinhibitory vasovagal syncope ( P < .05)., Conclusion: Compared with children with mixed/cardioinhibitory vasovagal syncope, oral rehydration salt is more suitable for those with vasodepressor vasovagal syncope.

The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.

Background Oral rehydration salt (ORS) is an affordable and effective intervention for the management of acute watery diarrhoea (AWD), especially in children under 5 years. A knowledge/practice gap exists among community pharmacists (CPs) in Lagos, Nigeria, and in many low to middle income countries. This gap results in underutilization of ORS for diarrhoea management. Objective The objective was to explore CPs' views of the barriers and facilitators to the use of ORS in practice. Setting Community pharmacy practices, Lagos, Nigeria. Methods Qualitative methods were used to explore pharmacists' views. Recruitment of participants were mainly at zonal meetings. A total of ten CPs participated based on maximum variation and snowballing sampling. Semi-structured interviews conducted covered knowledge, experiences and contextual issues. Interviews were audiorecorded, transcribed and analysed using framework approach to thematic analysis. Main outcome measure Pharmacists' views of barriers and facilitators to the use of ORS. Results Barriers to the use of ORS include caregivers' expectation for an antimicrobial, which was often explicitly and specifically for metronidazole. Also, CPs seemed to doubt applicability of ORS alone, therefore, responded to caregivers' complaints about ORS, by dispensing metronidazole. These barriers appeared to have normalised metronidazole for AWD treatment in this setting. Current facilitators include the caregivers' improved awareness of ORS and access to primary health centers that often resulted in increased demand for ORS in pharmacies. Conclusion CPs' views showed that caregivers' expectations for an antimicrobial may be the main barrier to the use of ORS in their practices.

Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release high levels of proteases and reactive oxygen species (ROS). While low levels of ROS play a fundamental role in the regulation of normal wound healing, their levels need to be tightly regulated to prevent a hostile wound environment resulting from excessive levels of ROS. Infection amplifies the inflammatory response, augmenting levels of ROS which creates additional tissue damage that supports microbial growth. Antimicrobial dressings are used to combat infection; however, the effects of these dressing on the wound environment and healing independent of infection are rarely assessed. Cytotoxic or adverse effects on healing may exacerbate the hostile wound environment and prolong healing. Here we assessed the effect on healing independent of infection of silver oxysalts which produce higher oxidative states of silver (Ag 2+ /Ag 3+ ). Silver oxysalts had no adverse effect on fibroblast scratch wound closure whilst significantly promoting closure of keratinocyte scratch wounds (34% increase compared with control). Furthermore, dressings containing silver oxysalts accelerated healing of full-thickness incisional wounds in wild-type mice, reducing wound area, promoting reepithelialization, and dampening inflammation. We explored the mechanisms by which silver oxysalts promote healing and found that unlike other silver dressings tested, silver oxysalt dressings catalyze the breakdown of hydrogen peroxide to water and oxygen. In addition, we found that silver oxysalts directly released oxygen when exposed to water. Collectively, these data provide the first indication that silver oxysalts promote healing independent of infection and may regulate oxidative stress within a wound through catalysis of hydrogen peroxide., (© 2018 by the Wound Healing Society.)

Background: Many interventions have attempted to increase vulnerable and remote populations' access to ORS and zinc to reduce child mortality from diarrhoea. However, the impact of these interventions is difficult to measure. From 2010 to 15, Micronutrient Initiative (MI), worked with the public sector in Bihar, India to enable community health workers to treat and report uncomplicated child diarrhoea with ORS and zinc. We describe how we estimated programme's impact on child mortality with Lives Saved Tool (LiST) modelling and data from MI's management information system (MIS). This study demonstrates that using LiST modelling and MIS data are viable options for evaluating programmes to reduce child mortality., Methods: We used MI's programme monitoring data to estimate coverage rates and LiST modelling software to estimate programme impact on child mortality. Four scenarios estimated the effects of different rates of programme scale-up and programme coverage on estimated child mortality by measuring children's lives saved., Results: The programme saved an estimated 806-975 children under-5 who had diarrhoea during five-year project phase. Increasing ORS and zinc coverage rates to 19.8% & 18.3% respectively under public sector coverage with effective treatment would have increased the programme's impact on child mortality and could have achieved the project goal of saving 4200 children's lives during the five-year programme., Conclusions: Programme monitoring data can be used with LiST modelling software to estimate coverage rates and programme impact on child mortality. This modelling approach may cost less and yield estimates sooner than directly measuring programme impact with population-based surveys. However, users must be cautious about relying on modelled estimates of impact and ensure that the programme monitoring data used is complete and precise about the programme aspects that are modelled. Otherwise, LiST may mis-estimate impact on child mortality. Further, LiST software may require modifications to its built-in assumptions to capture programmatic inputs. LiST assumes that mortality rates and cause of death structure change only in response to changes in programme coverage. In Bihar, overall child mortality has decreased and diarrhoea seems to be less lethal than previously, but at present LiST does not adjust its estimates for these sorts of changes.

Background: Diarrhoea is a leading cause of child death in Zambia. As elsewhere, the disease burden could be greatly reduced through caregiver uptake of existing prevention and treatment strategies. We recently reported the results of the Komboni Housewives intervention which tested a novel strategy employing motives including affiliation and disgust to improve caregiver practice of four diarrhoea control behaviours: exclusive breastfeeding; handwashing with soap; and correct preparation and use of oral rehydration salts (ORS) and zinc. The intervention was delivered via community events (women's forums and road shows), at health clinics (group session) and via radio. A cluster randomised trial revealed that the intervention resulted in a small improvement in exclusive breastfeeding practices, but was only associated with small changes in the other behaviours in areas with greater intervention exposure. This paper reports the findings of the process evaluation that was conducted alongside the trial to investigate how factors associated with intervention delivery and receipt influenced caregiver uptake of the target behaviours., Methods: Process data were collected from the eight peri-urban and rural intervention areas throughout the six-month implementation period and in all 16 clusters 4-6 weeks afterwards. Intervention implementation (fidelity, reach, dose delivered and recruitment strategies) and receipt (participant engagement and responses, and mediators) were explored through review of intervention activity logs, unannounced observation of intervention events, semi-structured interviews, focus groups with implementers and intervention recipients, and household surveys. Evaluation methods and analyses were guided by the intervention's theory of change and the evaluation framework of Linnan and Steckler., Results: Intervention reach was lower than intended: 39% of the surveyed population reported attending one or more face-to-face intervention event, of whom only 11% attended two or more intervention events. The intervention was not equally feasible to deliver in all settings: fewer events took place in remote rural areas, and the intervention did not adequately penetrate communities in several peri-urban sites where the population density was high, the population was slightly higher socio-economic status, recruitment was challenging, and numerous alternative sources of entertainment existed. Adaptations made by the implementers affected the fidelity of implementation of messages for all target behaviours. Incorrect messages were consequently recalled by intervention recipients. Participants were most receptive to the novel disgust and skills-based interactive demonstrations targeting exclusive breastfeeding and ORS preparation respectively. However, initial disgust elicitation was not followed by a change in associated psychological mediators, and social norms were not measurably changed., Conclusions: The lack of measured behaviour change was likely due to issues with both the intervention's content and its delivery. Achieving high reach and intensity in community interventions delivered in diverse settings is challenging. Achieving high fidelity is also challenging when multiple behaviours are targeted for change. Further work using improved tools is needed to explore the use of subconscious motives in behaviour change interventions. To better uncover how and why interventions achieve their measured effects, process evaluations of complex interventions should develop and employ frameworks for investigation and interpretation that are structured around the intervention's theory of change and the local context., Trial Registration: The study was registered as part of the larger trial on 5 March 2014 with ClinicalTrials.gov: NCT02081521 .

Hypocalcemia is a serious condition which has a major impact on the transmission of nerve impulses, contraction and relaxation of muscles (including myocardial) and pathological secretion of some hormones. The basic causal treatment is the parenteral administration of calcium, namely calcium gluconate, calcium chloride or calcium gluceptate. Parenteral formulations of these compounds must meet pharmacopoeial requirements, including the aluminum content limit. Each of these molecules has its specific properties that predict their clinical use. In addition to hypocalcemia, they are used to influence a variety of other conditions, such as fluoride or oxalic acid poisoning, decreased myocardial contractility caused by overdose of calcium intake blockers or beta blockers. They are also used as part of parenteral nutrition AIO or as an ancillary treatment for acute allergic conditions, itchy dermatitis, weeping and generalized eczema, continuous renal replacement therapy, seizure convulsion, laryngospasm, bronchospasm and altered mental status. The role of calcium replacement in septic patients remains unclear and requires further study. Although it may appear that calcium chloride infusion solutions provide greater and more highly ionized amounts of calcium, gluconate salts are preferred due to considerably less irritation of the vessel wall and better compatibility with other nutrients in parenteral nutrition.Key words: hypocalcemia calcium gluconate calcium chloride aluminum parenteral nutrition.

Background: Chronic rhinosinusitis (CRS) is a common health problem. If medical treatment fails, endonasal sinus surgery is a valuable treatment option. A thorough postsurgical treatment is needed including, among others, nasal saline irrigations (NSI). In this prospective, controlled, single blinded, randomized trial, we aimed to evaluate efficacy of nasal saline irrigations following endonasal sinus surgery in CRS-patients with nasal polyps., Methodology: We examined patient's nasal symptoms, general quality of life and postoperative condition of the mucosa. We also investigated whether or not NSI reduced the number of missed workdays after surgery (MWD). Patients were randomized into an irrigation and non-irrigation arm., Results: Following treatment, mean nasal sum-score in the irrigation arm was 4.4 and in the non-irrigation arm it was 6.3. Accordingly, mean general sum-score in the irrigation arm was 2.5 and in the non-irrigation arm 4.8. Thus, nasal irrigation led to a more pronounced improvement of nasal and general symptoms than in the non-irrigation arm. No differences were observed in postoperative condition of mucosa or number of MWD., Conclusions: Nasal irrigation improves symptoms score after ESS in patients with CRSwNP.

Background: Presumably bundling/co-packaging of zinc with ORS encourages the combined use of the products for diarrhea treatment; however, empirical evidences are scarce. The purpose of this work is to evaluate whether co-packing using a plastic pouch can enhance the joint adherence to the treatment or not. The study also compares the cost effectiveness (CE) of two co-packaging options: 'central' and 'health center (HC)' level bundling., Methods: This cluster-randomised controlled trial was conducted in 2015 in eight districts of Ethiopia. Thirty two HCs were randomly assigned to one of the following four intervention arms: (i) 'Central bundling' (zinc and ORS bundled using a pouch that had instructional message, distributed to HCs); (ii) 'HC level bundling' (zinc, ORS and a similar pouch distributed to the HCs and bundled by health workers); (iii) 'Bundling without message' (zinc, ORS and plain pouch distributed and bundled by the health workers); and, (iv) 'Status quo' (zinc and ORS co-administered without bundling). In each of the four arms, 176 children 6-59 months of age, presented with acute diarrhea were enrolled. Twelve days after enrollment, level of adherence was assessed. A composite scale of adherence was developed and modeled using mixed effects linear regression analysis. The unit costs associated with the arms were estimated using secondary data sources. Incremental CE analysis was made by taking the cost and level of adherence in fourth arm as a base value., Results: The follow-up rate was 95.6 %. As compared with the 'status quo' arm, the joint adherences in the 'central' and 'HC level' bundling arms raised substantially by 14.8 and 15.7 percentage points (PP), respectively (P < 0.05). No significant difference was observed between 'bundling without message' and the 'status quo' arms. The unit cost incurred by the 'central bundling' is relatively higher (USD 0.658/episode) as compared with the 'HC level bundling' approach (USD 0.608/episode). The incremental CE ratio in the 'central bundling' modality was two times higher than in the 'HC based bundling' approach., Conclusion: Bundling zinc with ORS using a pouch with instructional messages increases adherence to the treatment. 'HC level bundling' is more CE than the 'central bundling' approach.

Background: A theoretically grounded formative research study was carried out to investigate behaviour related to the use of Oral Rehydration Salts (ORS) and zinc tablets. The purpose was to inform the design of the behaviour change component of the Programme for Awareness and Elimination of Diarrhoea in Lusaka Province, Zambia, which aims to reduce childhood morbidity and mortality from diarrhoeal disease., Methods: Fourteen behaviour trials were conducted among caregivers of children under-five with diarrhoea. Caregivers were recruited from two clinics situated in rural and peri-urban Lusaka. Trials took ten days and data were captured using video, observation and repeated interviews. Additional data were collected through focus group discussions with mothers, observations in clinics and pharmacies and interviews with clinic and pharmacy staff. Findings were organised according to categories of behavioural determinants from Evo-Eco theory., Results: Participants were all familiar with ORS and most knew its purpose. ORS use was motivated by symptoms of dehydration, rather than the start of a diarrhoea episode, and was stopped when the child had visibly recovered energy. Only four of 14 behaviour trial participants were observed to correctly prepare ORS. Errors were mainly associated with measurement, resulting in a solution that was too concentrated. ORS was not observed to be given to children at clinics. Although zinc was unknown in this population, it was positively received by mothers keen to learn whether zinc would work better than alternative treatments to stop diarrhoea., Conclusions: ORS was sub-optimally prepared and used at home. It was not used while waiting to be seen at a clinic. In homes, the behaviour change intervention should promote early and continued use of correctly prepared ORS. In the longer-term, these behaviours may best be encouraged by changing the product design or sachet size. Despite its unfamiliarity, this population was well disposed to the use of zinc as a treatment for diarrhoea; when zinc is new to a population, promoting zinc as a solution to stopping diarrhoea, which mothers seek, may drive initial trial. Ensuring the availability of zinc in public clinics and private pharmacies prior to commencement of any promotion activities is crucial.

Hydrogen sulfide (H2S), a colorless gas smelling of rotten egg, has long been considered a toxic gas and environment hazard. However, evidences show that H2S plays a great role in many physiological and pathological activities, and it exhibits different effects when applied at various doses. In this review, we summarize the chemistry and biomedical applications of H2S-releasing compounds, including inorganic salts, phosphorodithioate derivatives, derivatives of Allium sativum extracts, derivatives of thioaminoacids, and derivatives of antiinflammatory drugs.

Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis., (© 2016 S. Karger AG, Basel.)