Haem iron versus ferrous iron salts to treat iron deficiency anaemia in Gambian children: protocol for randomised controlled trial {1}.

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.

Screening for new ligands of the MB327-PAM-1 binding site of the nicotinic acetylcholine receptor.

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 [2H6]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 IC50 value of ≤ 10 µM (in the [2H6]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 pKi 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.

A Single-Blind, Placebo Controlled Trial of Triple Beaded Mixed Amphetamine Salts in DSM-5 Adults With ADHD Assessing Effects Throughout the Day.

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.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

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.

Neurological complications due to copper deficiency in the context of Wilson disease treatment: a case report with long-term follow-up and review of the literature.

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.

Mixed amphetamine salts-extended release (MAS-ER) as a behavioral treatment augmentation strategy for cocaine use disorder: A randomized clinical trial.

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).

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.

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.

Lithium, a Treatment Option for Alzheimer's Disease? A Review of Existing Evidence and Discussion on Future Perspectives.

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-3ß 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.

Switching patterns of immediate-release forms of generic mixed amphetamine salts products among privately and publicly insured individuals aged 15-64 years in the United States, 2013-2019.

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.

The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.

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.

Clinical Efficacy of Mouthwashes with Potassium Salts in the Treatment of Dentinal Hypersensitivity: A Systematic Review and Meta-analysis.

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.

Mixed Amphetamine Salts Without a Mood Stabilizer for Treating Comorbid Attention-Deficit Hyperactivity Disorder and Bipolar Disorder: Two Case Reports.

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.

Treatment options in hypoparathyroidism.

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.

Biologically synthesized black ginger-selenium nanoparticle induces apoptosis and autophagy of AGS gastric cancer cells by suppressing the PI3K/Akt/mTOR signaling pathway.

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.

Comparative Study between Acacia Nilotica versus Povidone Iodine in Topical Treatment of Omphalocele Major.

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.

[Can salt substitution or reduction replace pharmaceuticals for arterial hypertension?] / Kann eine Salzsubstitution oder -reduktion bei arterieller Hypertonie Arzneimittel ersetzen?

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.

Experimental data on lithium salts: From neuroprotection to multi-organ complications.

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 ß-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.

Regression of calcinosis cutis after inkless tattoo in a patient with dermatomyositis: therapeutic potential of microneedling.

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.

Etiology-based dietary approach for managing hyperkalemia in people with chronic kidney disease.

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.

Functionalized 1,2,3-triazolium salts as potential agents against visceral leishmaniasis.

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 IC50 range from 0.12 to 8.66 µM and, among them, compound 5 showed significant activity against promastigotes (IC50 from 4.55 to 5.28 µM) and intracellular amastigotes (IC50 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.