MiXie, an Online Tool for Better Health Assessment of Workers Exposed to Multiple Chemicals

There is increasing concern for workers facing multiple chemical exposure. The accumulation of information on occupational conditions indicates the need to incorporate the concept of multiple exposures in the risk assessment process and to develop tools for assessing the potential impacts of multiple exposures on workers’ health. Our objective is to describe the MiXie online decision-making tool that can be used to assess the risk of exposure to multiple chemicals. The description includes the development of MiXie, the structure of its toxicological database according to the target organ or the mode of action, and the algorithm for quantitative analysis of a mixture. Two case studies of its use in evaluating the risks of multiple exposures in real workplace situations are presented. The case study in the printing industry showed increased risk for four toxicological classes (central nervous system damage, ocular damage, skin damage, and ototoxicity) associated with co-exposure to four chemicals during maintenance operations. The MiXie analysis also showed the presence of carcinogenic substances in the mixture and a risk to the development of the foetus. The case study in nail salons showed the presence of carcinogenic and sensitizing chemicals and an increased risk to upper airways. MiXie helps preventers evaluate the possible additive effects of mixtures, providing an easy-to-read diagnosis to identify risks incurred by co-exposed employees. In addition, MiXie identifies risky occupational situations that would go unnoticed without a multiple substance approach.

Approach To The Pediatric Patient: Central Diabetes Insipidus

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow up. Early diagnosis and treatment are crucial in order to avoid central nervous system damage, germ cell tumor dissemination, and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with “apparently” idiopathic CDI is particularly emphasized, because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked, and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.

Special Medical Food in Premature Child with Postnatal Malnutrition: Clinical Case

Background. Protein-calorie deficiency is common multifactorial medical condition in infants. Nutrition therapy of protein-calorie deficiency in premature infants with special medical food is not always quite effective. It can be associated with residual manifestations of overlapping perinatal pathology.Clinical case description. Extremely premature child with severe protein-calorie deficiency in the late period with combined perinatal pathology (perinatal central nervous system damage and bronchopulmonary dysplasia) was administrated with therapeutic highly nutritious (high-protein/high-energy) milk formula according to individual plan. The positive dynamics in clinical manifestations of the main and associated diseases was noted on nutrition therapy.Conclusion. High-calorie and protein-enriched therapeutic formula can effectively correct protein-calorie deficiency in premature infants with associated perinatal pathology in the recovery period (disfunction compensation).

Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a

Approximately 2 million individuals experience a traumatic brain injury (TBI) every year in the United States. Secondary injury begins within minutes after TBI, with alterations in cellular function and chemical signaling that contribute to excitotoxicity. Post-traumatic seizures (PTS) are experienced in an increasing number of TBI individuals that also display resistance to traditional anti-seizure medications (ASMs). Sonic hedgehog (Shh) is a signaling pathway that is upregulated following central nervous system damage in zebrafish and aids injury-induced regeneration. Using a modified Marmarou weight drop on adult zebrafish, we examined PTS following TBI and Shh modulation. We found that inhibiting Shh signaling by cyclopamine significantly increased PTS in TBI fish, prolonged the timeframe PTS was observed, and decreased survival across all TBI severities. Shh-inhibited TBI fish failed to respond to traditional ASMs, but were attenuated when treated with CNQX, which blocks ionotropic glutamate receptors. We found that the Smoothened agonist, purmorphamine, increased Eaat2a expression in undamaged brains compared to untreated controls, and purmorphamine treatment reduced glutamate excitotoxicity following TBI. Similarly, purmorphamine reduced PTS, edema, and cognitive deficits in TBI fish, while these pathologies were increased and/or prolonged in cyclopamine-treated TBI fish. However, the increased severity of TBI phenotypes with cyclopamine was reduced by cotreating fish with ceftriaxone, which induces Eaat2a expression. Collectively, these data suggest that Shh signaling induces Eaat2a expression and plays a role in regulating TBI-induced glutamate excitotoxicity and TBI sequelae.

How Does Stroke Affect Skeletal Muscle? State of the Art and Rehabilitation Perspective

Long-term disability caused by stroke is largely due to an impairment of motor function. The functional consequences after stroke are caused by central nervous system adaptations and modifications, but also by the peripheral skeletal muscle changes. The nervous and muscular systems work together and are strictly dependent in their structure and function, through afferent and efferent communication pathways with a reciprocal “modulation.” Knowing how altered interaction between these two important systems can modify the intrinsic properties of muscle tissue is essential in finding the best rehabilitative therapeutic approach. Traditionally, the rehabilitation effort has been oriented toward the treatment of the central nervous system damage with a central approach, overlooking the muscle tissue. However, to ensure greater effectiveness of treatments, it should not be forgotten that muscle can also be a target in the rehabilitation process. The purpose of this review is to summarize the current knowledge about the skeletal muscle changes, directly or indirectly induced by stroke, focusing on the changes induced by the treatments most applied in stroke rehabilitation. The results of this review highlight changes in several muscular features, suggesting specific treatments based on biological knowledge; on the other hand, in standard rehabilitative practice, a realist muscle function evaluation is rarely carried out. We provide some recommendations to improve a comprehensive muscle investigation, a specific rehabilitation approach, and to draw research protocol to solve the remaining conflicting data. Even if a complete multilevel muscular evaluation requires a great effort by a multidisciplinary team to optimize motor recovery after stroke.

Enzyme Replacement Therapy with Idursulfase in Patients with Mucopolysaccharidosis Type II: Literature Review

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is X-linked hereditary disease from the group of lysosomal storage disease. Its prevalence is 3–7 cases per 1 million live-born boys. MPS II occurs due to the deficiency of iduronate-2-sulfatase enzyme because of pathological changes in the structure of the IDS gene. Enzyme deficiency leads to the accumulation of glycosaminoglycans (GAGs), dermatan sulfate and heparan sulfate, in lysosomes. This leads to the damage of various organs and systems in the body with further development of clinical picture of the disease: coarse face, recurrent infections of upper respiratory tract, hearing loss up to deafness, cardiovascular and respiratory systems pathologies, hepatosplenomegaly, musculoskeletal system abnormalities, low growth, central nervous system damage. Enzyme replacement therapy with idursulfase, that was introduced in clinical practice 15 years ago, has significantly changed the quality of life of these patients. Idursulfase is purified form of natural lysosomal enzyme iduronate-2-sulfatase obtained via human cell line. Exogenous enzyme entry promotes GAGs catabolism in cells. This article provides outcomes analysis of foreign and Russian studies on the efficacy and safety of this medication, and its effect on MPS II patients survivability.

Cochlea implantation in patients with superficial hemosiderosis

Introduction Superficial hemosiderosis is a sub-form of hemosiderosis in which the deposits of hemosiderin in the central nervous system damage the nerve cells. This form of siderosis is caused by chronic cerebral hemorrhages, especially subarachnoid hemorrhages. The diversity of symptoms depends on the respective damage to the brain, but in most of the cases it shows up as incipient unilateral or bilateral hearing loss, ataxia and signs of pyramidal tracts. We are investigating the question of whether cochlear implantation is a treatment option for patients with superficial hemosiderosis and which strategy of diagnostic procedure has to be ruled out preoperatively. Materials and methods In a tertiary hospital between 2009 and 2018, we examined (N = 5) patients with radiologically confirmed central hemosiderosis who suffered from profound hearing loss to deafness were treated with a cochlear implant (CI). We compared pre- and postoperative speech comprehension (Freiburg speech intelligibility test for monosyllables and HSM sentence test). Results Speech understanding improved on average by 20% (monosyllabic test in the Freiburg speech intelligibility test) and by 40% in noise (HSM sentence test) compared to preoperative speech understanding with optimized hearing aids. Discussion The results show that patients with superficial siderosis benefit from CI with better speech understanding. The results are below the average for all postlingual deaf CI patients. Superficial siderosis causes neural damages, which explains the reduced speech understanding based on central hearing loss. It is important to correctly weigh the patient's expectations preoperatively and to include neurologists within the therapy procedure.

Neurological aspects of COVID-19

The coronavirus disease COVID-19 began to spread worldwide in December 2019 from the city of Wuhan (China). COVID-19 is often accompanied by fever, hypoxemic respiratory failure and systemic complications (for example, gastrointestinal, renal, cardiac, neurological, and hepatic lesions), thrombotic phenomena. Central nervous system damage is caused by the primary effect on it, direct neuroinvasion of the virus, and more often by secondary effect due to systemic hyperinflammation. Neurological manifestations include fatigue, headache, insomnia, and olfactory/taste disorders. Neurological manifestations and complications of COVID-19 are diverse: (1) cerebral circulatory disorders, including ischemic stroke and macro/microhemorrhages; (2) encephalopathy; (3) para/postinfectious autoimmune complications, such as GuillainBarre syndrome; (4) meningoencephalitis; (5) neuropsychiatric complications (psychosis and mood disorders). In terms of pathogenesis, neurological disorders in COVID-19 can be caused by neurotropicity and neurovirulence of SARS-CoV-2, cytokine storm, hypoxemia, homeostasis disorders, as well as their combined effects. COVID-19 adversely affects the course and prognosis of chronic neurological disorders in comorbid patients. The review highlights the need for vigilance to early neurological complications in patients infected with SARS-CoV-2 and other coronaviruses, especially since some neurological complications may precede respiratory manifestations.

West nile fever case in neurological practice

West Nile fever is a zoonotic arbovirus mosquito- and tick-borne infection, which occurs in humans in the form of an acute febrile illness with symptoms of general intoxication, in severe cases – with the central nervous system damage. West Nile virus belongs to the Flaviviridae family.After the start of Russians’ mass tourism to tropical and subtropical regions, number of cases of the disease in Russia has increased, especially in the south, where the virus is more viable. The infection mainly affects birds but also people and many mammals (bats, cats, dogs, skunks, squirrels, rabbits, etc.), which become infected after the bite of a mosquito of the genus Culex (Culex pipiens) carrying the disease, ixodid or argas mite. A clinical case of hemorrhagic stroke caused by West Nile fever is presented in the article.

The Risk Factors for Development of Emergency Conditions in Tender-Age Infants in Acute Intestinal Infections of Different Etiologies

Among the leading risk factors for the development of emergency conditions in acute intestinal infections, especially in infants, some authors point to rickets, anemia, and abnormal antenatal pathology. The aim is to determine the frequency of occurrence of various risk factors for the development of emergency situations in tender-age infants. Materials and methods: 338 tender-age infants with urgent conditions were under observation. The study involved clinical-anamnestic, bacteriological, and serological methods. The aggravating factors were as follows: diseases of parents in 16 (6.2%), related marriages - 20 (7.7%) pregnancy pathology-137 (52.9%), prematurity-16 (6.2%), artificial feeding - 127 (49.0%), early diseases (acute respiratory viral infections, pneumonia, encephalopathy, intestinal infections). Results: According to the results of the study, the central nervous system damage was most often observed in children from 1 month to 6 months (80.2%), anemia was more detected in children of 1-3 years - 56.4%, rickets was more diagnosed in children aged 6-12 months -38.2%.