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The multi-component solid form of febuxostat (FEB) with p-toluenesulfonic acid was synthesized by solvent-drop grinding and cooling-evaporative crystallization and characterized by powder X-ray diffraction (XRPD), thermogravimetry (TGA), differential scanning calorimetry (DSC), and infrared spectroscopy (FT-IR). The multi-component form was stable after exposure at elevated temperature and relative humidity and powder dissolution measurements revealed five-fold aqueous solubility improvement relative to FEB. Additionally, the decrease in pH after dissolution suggests a potential for enhancing the drug absorption in the lower stomach. In the context of the regulatory requirements, the salt/co-crystal nature of the form was elucidated by a combination of crystallization process development and crystal growth, followed by SC-XRD and FT-IR. Despite the very weak basicity of the drug, crystal structure determination combined with spectroscopy analysis revealed salt formation by the transfer of the acidic proton from p-toluenesulfonic acid to FEB. Our study emphasizes the importance of the crystal structure knowledge in understanding the type of interactions present in multi-component crystals as well as complying with the specific regulatory requirements.

In this paper we discuss the classification results of cardiac patients of ischemical cardiopathy, valvular heart disease, and arterial hypertension, based on 19 characteristics (descriptors) including ECHO data, effort testings, and age and weight. In this order we have used different fuzzy clustering algorithms, namely hierarchical fuzzy clustering, hierarchical and horizontal fuzzy characteristics clustering, and a new clustering technique, fuzzy hierarchical cross-classification. The characteristics clustering techniques produce fuzzy partitions of the characteristics involved and, thus, are useful tools for studying the similarities between different characteristics and for essential characteristics selection. The cross-classification algorithm produces not only a fuzzy partition of the cardiac patients analyzed, but also a fuzzy partition of their considered characteristics. In this way it is possible to identify which characteristics are responsible for the similarities or dissimilarities observed between different groups of patients.

High-power PW laser systems (HPLS) provide intense beams of accelerated reaction-driving protons simultaneously with spatially localized keV-plasmas. We herein depict our groundwork and strategy to use these unique features of the HPLS at the Extreme Light Infrastructure (ELI-NP) by exposing the long-lived nuclear isomer 93 m Mo at 2.425 MeV ( t 1 / 2 = 6.85 h) to plasma facilitating the local petawatt beamlines. An intermediate short-lived ( t 1 / 2 = 3.52 ns) state situated only 4.85 keV above 93 m Mo constitutes a gateway to allow for its prompt release. The controllable release of the nuclear isomer energy will henceforth enable harvesting energy densities in the nuclear regime of GJkg - 1 (‘Nuclear Battery’). The campaign was inspired by the observation of the triggered release of 93 m Mo via the intermediate state by Chiara et al. [1] published in Nature. They assigned the hitherto elusive Nuclear Excitation by Electron Capture (NEEC) as the driving process and claimed a very high probability of P NEEC exp = 0.010 (3) . However, these claims are challenged by experimentalists [2-3] and theory [4]. We herein outline our strategy following bespoke theoretical guidance in the quest to unambiguously and independently demonstrate the onset of NEEC in 93 m Mo . With the yield estimations derived for our forthcoming HPLS experiment at ELI-NP, we draw optimism to resolve the current conundrum between the conflicting experimental observations and theoretical interpretations as discussed in world-leading journals and to pave the way for the future utilization of isomer depopulation in applied physics. [ABSTRACT FROM AUTHOR]

Activated carbons have great applicability in the conditioning of wines: discoloration, removal of foreign taste and smell, correction of organoleptic parameters, etc. The purpose of this work was to compare the structural and sorption characteristics of local vegetal activated carbon obtained from apricot stones (AC-C, Republic of Moldova) with that of commercial activated carbons (Granucol® BI/GE/FA, Germany). The physico-chemical characteristics of studied activated carbons have been evaluated by standard methods (nitrogen sorption isotherms, IR spectroscopy, pH value of activated carbons suspension etc.) and the adsorption capacity by using methylene blue dye as a reference substance. Experimental data were analysed by theoretical models: Langmuir and Equilibrium isotherm models, and pseudo-first-order, and pseudo-second-order kinetic models. The adsorption capacity of the local activated carbon (AC-C, 690 mg/g) is higher by 30% than that of activated carbons from Granucol® series (approx. 535 mg/g).

BackgroundAlström disease is a rare disorder caused by various variants in the ALMS1 gene. It is characterised by multiorgan involvement, namely neurosensory deficits, endocrine and metabolic disturbances, cardiomyopathy, and hepatic and renal dysfunction. The disease exhibits marked interindividual variability, both in clinical manifestations and age of onset. Several attempts have been made to establish a relationship between phenotype and genotype, with little success.MethodsWe present the case of an infant who presented with dilated cardiomyopathy, above-average weight and neurosensory deficits, raising the suspicion for Alström syndrome, later confirmed through genetic testing. Moreover, we conducted an extensive literature search to identify all reported cases having the same variant as our patient, in order to evaluate whether specific mutated alleles have a role in determining phenotype-genotype associations.ResultsA 4-month-old female infant with a recent history of bronchiolitis was referred to our centre due to a systolic murmur. In our service, the clinical exam was significant for above-average weight, dyspnea, wheezing and a grade II systolic murmur. Echocardiography revealed dilated cardiomyopathy with severe systolic dysfunction of the left ventricle. Laboratory investigations revealed elevated NT-proBNP and troponin levels, along with positive IgM antibodies for CMV and EBV. Dilated cardiomyopathy attributed to viral myocarditis was suspected. Treatment with ACE inhibitors and diuretics was started, with a favourable response initially. However, after a few months, the patient presented with vertical nystagmus and head bobbing. The ophthalmologic exam revealed cone-rode dystrophy. Considering the constellation of symptoms, Alström syndrome was suspected. Genetic testing revealed a homozygous variant [c.4156dup (p.Thr1386Asnfs*15)] in the ALMS1 gene, confirming the diagnosis.ConclusionOur literature review revealed 8 additional cases harbouring the same variant as our patient, five in a heterozygous state, two in a homozygous state and one with only one allele identified. The identified patients presented high heterogeneity of clinical manifestations and age of onset. The heterogeneity persisted even in patients with homozygous variants, suggesting the involvement of factors beyond the specific disease-causing variant in determining disease manifestation. Therefore, genotype-phenotype correlations might not be supported by specific variants.

Wilson's disease (WD) is a rare disorder of the copper metabolism with an autosomal recessive transmission. In children, the most frequent clinical presentation is liver disease, variable from increased transaminases to liver cirrhosis or acute liver failure. In young adulthood, the main forms could be neurological and psychiatric.A high level of suspicion should be present for an early diagnosis of WD, as the diagnosis is based on a combination of clinical signs, biochemical tests, histology, and genetics. The Kayser-Fleisher ring is not as frequent in children as in adults. In children, 24-hour urinary copper excretion could be in the normal range, and the d-penicillamine challenge test should be used. During the last few years, genetic tests have become more affordable, helping with the final diagnosis of WD.An early diagnosis and treatment could improve the evolution of WD in children, but in some cases, the only option for long-term survival could be liver transplantation. Besides the zinc salts and chelating agents (d-penicillamine and trientine), other molecules have been researched to improve the treatment of WD. Also, gene therapy could represent the solution in the future, but there are issues regarding the vectors and the gene dimensions before this therapy may be used on a large scale. Studies regarding the screening for WD lead to evidence of possible ATP7B peptides that could be measured for an early diagnosis.Besides all the possible advances in diagnosis and treatment, the patient's adherence to treatment influences the long-term prognosis. Increasing awareness and improving policies for rare diseases may give WD patients access to adequate care and services throughout Europe.

Background: In children, acute liver failure (ALF) is a severe condition associated with high mortality if an emergency liver transplantation (LT) is impossible. Clinical laboratory parameters and different scores or criteria are used to predict ALF evolution in children. We aimed to assess the role of coagulation factors as predictive markers of poor outcomes in children with ALF. Methods: The prospective study included 40 children with ALF, diagnosed based on the Pediatric ALF study group criteria. Patients with emergency LT or deceased were considered with poor outcomes. For all patients, we analyzed clinical and laboratory parameters (including plasma level of factor V (FV), factor VII (FVII), and INR). We calculated the PELD (Pediatric End-stage Liver Disease) and MELD (Model for End-stage Liver Disease) scores, King's College Hospital (KCH), and Clichy criteria. We analyzed their performance in predicting a poor outcome. Results: FV and FVII levels were significantly lower in children with poor outcomes than survivors (18.92 ± 19.95% vs. 10.72 ± 10.21%, p = 0.00139, respectively 46.51 ± 26.05% vs. 10.72 ± 10.21%, p = 0.00014). These parameters varied with ALF etiology, being the lowest in metabolic and infectious causes. The maximum value of INR (INR-max) was higher in children with poor outcomes than survivors (7.05 ± 3.20 vs. 2.96 ± 1.82, p = 0.000007), as it also was for the PELD/MELD score (30.06 ± 15.55 vs. 15.77 ± 9.64, p = 0.00092). FVII, FV, and INR-max had an excellent performance in predicting the poor outcome with an area under the ROC curve of 0.894, 0.816, and 0.861, respectively. KCH criteria had a higher sensitivity than Clichy criteria (92.86% vs. 50%) but lower specificity (53.85% vs. 95%). Conclusions: Our results support the role of coagulation factors (INR, FV, and FVII) as predictive markers for the fatal evolution of children with ALF and underlined the need for monitoring along with the usual liver function tests in children with ALF. [ABSTRACT FROM AUTHOR]

Abstract Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases.

Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient’s need for comfort and lack of distress with the clinicians’ need for adequate information regarding the patient’s glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.

Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.

The process of the kinetics of caffeine adsorption from aqueous solutions on activated carbon AC-0-9, obtained from apple wood, was studied. The analyses of nitrogen adsorption-desorption isotherms demonstrated that this carbon adsorbent is basically mesoporous. The pseudo-two model describes best the kinetic process, highlighting the role of functional groups on the activated carbon surface. The pseudo-one model only initially describes the kinetic process of caffeine adsorption on this activated carbon. It was found that the kinetics of the adsorption process of caffeine on AC-0-9 activated carbon takes place in two stages. In the first stage, the speed of intraparticle diffusion is high, due to the adsorption of caffeine molecules in macro- and mesopores, and in the second stage, the speed of intraparticle diffusion is low, given the fact that adsorption takes place in micro- and supermicropores.

This paper presents the the main scientific and innovative results are presented, which were obtained by the talented chemist and renowned ecologist Valeriu Ropot throughout his scientific career. The results of scientific investigations are bestowed and analysed concerning the quality of the waters of the Dniester and the Prut Rivers, Dubasari reservoirs on the Dniester River, as well as the main bodies of water in the Republic of Moldova. The paper also includes the practical recommendations for reducing the negative impact on the environment, of the discharge of hundreds of thousands of tons of brine into the Dniester River as a result of the accident at the mineral fertilizer plant in the city of Stebnik, Ukraine. Moreover, the paper presents the results of studies aimed at developing methods for determining organic and inorganic pollutants in natural waters.

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Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021–September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

We present a case study who underlines the complexity of a rare form of microcephalic primordial dwarfism, also known as Seckel syndrome. This autosomal recessive disease, although very rare, requires a multidisciplinary approach in order to manage the neurologic, cardiovascular, hematologic, endocrinologic, metabolic and kidney related complications. Being a congenital nanosomic disorder, this condition can be suspected before birth if late second-semester or third-semester ultrasound indicates microcephaly in the context of symmetrical intrauterine growth restriction and the hallmark of a “bird-headed” appearance. Although born at normal gestational age, these patients have a very small birth-weight. Further in life, developmental issues with mild to moderate mental retardation install. Here, we present the case of an adult patient who was diagnosed during childhood, who needed specialized nephrological pediatric assistance because of her anthropometrical characteristics and end-stage renal disease (ESRD) of an uncertain etiology which required extra-renal epuration.

The adsorption of methylene blue and the kinetics of adsorption of aqueous solutions on activated carbon CAN-9, obtained from walnut shells by chemical activation with orthophosphoric acid were studied. It has been shown that the adsorption isotherm of methylene blue from aqueous solutions on CAN-9 in the linear coordinates of the Langmuir model is a straight line (R = 0.99427) and is of the Langmuir type. The kinetics of adsorption of methylene blue on CAN-9, measured at two initial concentrations, showed an increase in Kint and C values with the increase of the initial concentrations. The process of intra-particular diffusion occurs in only one stage and takes place in the mesopores.

Owing to increasing populations and global threats, the integrity and safety of global food chains are at risk. In many countries, simply getting enough to eat can be an issue, with poor quality food often contaminated with hazardous agents, whereas in developed countries the pressure to deliver cheap, affordable food may affect quality and safety. The purpose of this Special issue on Safe food for infants is to emphasize the importance of pursuing integrated approaches to monitor and reduce the risks of biological, chemical, and physical hazards in infant food. A careful integrated approach is proposed to be instrumental in order to minimize the hazards to infant health during the key developmental years and protect children from penalizing nutritional disorders and gastrointestinal diseases.

This article discusses the issue of food hazards and child health during the first thousand days of life. The aim is to raise the attention of decision makers, healthcare officers and professionals, including pediatricians, pediatric surgeons, obstetricians, nurses, midwives, dieticians and lactation consultants, on the importance of protecting infants and their families during a most critical period for the mother-child binomial. The conclusions emphasize the importance of encouraging the adoption of integrated strategies, useful at establishing adequate preventive efforts and a game-changing perspective shift in order to develop and adopt efficient monitoring strategies and procedures, able to minimize the risks due to hazards in food throughout the first thousand days of life, as a first line of prevention in children's health.

In this study, activated carbons derived from walnut shells (CA-N) and apple wood (CA-M) were used as adsorbents to remove cobalt(II) and strontium(II) ions from aqueous solutions. The novel materials were obtained using nitric acid (CA-Mox) and nitric acid/urea mixture (CA-Mox-u, CA-Nox-u) as oxidizing agents. The physical–chemical characteristics of activated carbons were determined from nitrogen sorption isotherms, SEM-EDX, FTIR, pH metric titrations, the Boehm titration method and elemental analysis. The results of batch experiments indicate that maximum adsorption can be achieved in broad pH ranges: 4–8 for Co(II) and 4–10 for Sr(II). The maximum adsorption capacities of Co(II) and Sr(II) on oxidized activated carbons at pH = 4 are: CA-Mox, 0.085 and 0.076 mmol/g; CA-Mox-u, 0.056 and 0.041 mmol/g; and CA-Nox-u, 0.041 and 0.034 mmol/g, respectively. The mathematical models (pseudo-first-order, pseudo-second-order and intraparticle diffusion kinetic models, and Langmuir, Freundlich, Dubinin–Radushkevich, and Temkin–Pyzhev isotherm models) were used to explain the adsorption kinetics, to study the adsorption mechanism and predict maximum adsorption capacity of the adsorbents. The adsorption mechanisms of toxic metal ions on activated carbons were proposed.