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Single-Event Multilevel Surgery (SEMLS) is the standard for surgical correction of secondary orthopedic deformities in cerebral palsy (CP). SEMLS include simultaneous correction of soft tissue contractures, bone deformities, incomplete and complete joint dislocation to improve the gait and functional activity of patients with CP. The surgery volume determines the need for planned and long-term postoperative rehabilitation, however, there are no confirmed guidelines, neither Russian, nor foreign, on the patient’s management during postoperative period. This review provides an analysis of rehabilitation approaches after SEMLS at CP, offers recommendations on preparation and step-by-step postoperative restoration of motor function, and prevention of any associated complications.

The increase in industrialization has led to an exponential increase in heavy metal (HM) soil contamination, which poses a serious threat to public health and ecosystem stability. This review emphasizes the urgent need to develop innovative technologies for the environmental remediation of intensive anthropogenic pollution. Phytoremediation is a sustainable and cost-effective approach for the detoxification of contaminated soils using various plant species. This review discusses in detail the basic principles of phytoremediation and emphasizes its ecological advantages over other methods for cleaning contaminated areas and its technical viability. Much attention has been given to the selection of hyperaccumulator plants for phytoremediation that can grow on heavy metal-contaminated soils, and the biochemical mechanisms that allow these plants to isolate, detoxify, and accumulate heavy metals are discussed in detail. The novelty of our study lies in reviewing the mechanisms of plant–microorganism interactions that greatly enhance the efficiency of phytoremediation as well as in discussing genetic modifications that could revolutionize the cleanup of contaminated soils. Moreover, this manuscript discusses potential applications of phytoremediation beyond soil detoxification, including its role in bioenergy production and biodiversity restoration in degraded habitats. This review concludes by listing the serious problems that result from anthropogenic environmental pollution that future generations still need to overcome and suggests promising research directions in which the integration of nano- and biotechnology will play an important role in enhancing the effectiveness of phytoremediation. These contributions are critical for environmental scientists, policy makers, and practitioners seeking to utilize phytoremediation to maintain the ecological stability of the environment and its restoration.

Congenital aniridia manifests with total or partial absence of the iris. The association of the disease with the PAX6 gene has been proven. Changes in the PAX6 structure lead to intrauterine pathology, visual organ malformation, malformation of master regulator proteins of organogenesis affecting various cells’ differentiation (central nervous system cells included). Such disorders result into the development of PAX6-associated syndromes with various brain malformations, neurological disorders, and systemic pathology (thyroid pathology, Wilms tumor, glucose intolerance). Isolated congenital aniridia is also accompanied by psychoneurological disorders. It can be associated with brain structures’ disorders during embryogenesis and with impact of external stress factors on the child (frequent medical checkup, surgical treatments). The psychoneurological disorders’ pathogenesis as well as congenital aniridia’s genetic mechanisms remain unclear. Thus, it is crucial to review new relevant data within the context of previously obtained information to gather full picture of the clinical signs of the disease and to improve the management of children with congenital aniridia.

In this study, the various amounts of poly-N-vinylpyrrolidone (PVPr) were added to the cement paste, and some parameters - flowing, initial and final setting points, water absorption, compressive strength, and flexural strength were determined. The concrete containing 0.8% PVPr exhibited high water absorption, specifically, at 14 and 28 days, increased from 15.65% to 20.71% and from 16.74% to 21.67%, respectively. The final setting time increased from 238 min to 261 min. It was determined that the compressive strength of the cement mortar increased from 54.8 MPa to 58.5 MPa when the PVPr content was 0.8–1.0%. The flexural strength also improved due to the presence of PVPr, increasing from 11.58 MPa to 14.27 MPa. According to the FTIR characterization, the PVPr macromolecule interacts with Ca2+ and Al3+ ions. TGA analysis reveals that the chemical interaction of PVPr with calcium and aluminum ions limits its mass loss up to 4–5% until 400 °C.

Background Acute myocardial infarction complicated by cardiogenic shock (AMI‐CS) is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) devices increase systemic blood pressure and end organ perfusion while reducing cardiac filling pressures. Methods and Results The National Cardiogenic Shock Initiative (NCT03677180) is a single‐arm, multicenter study. The purpose of this study was to assess the feasibility and effectiveness of utilizing early MCS with Impella in patients presenting with AMI‐CS. The primary end point was in‐hospital mortality. A total of 406 patients were enrolled at 80 sites between 2016 and 2020. Average age was 64±12 years, 24% were female, 17% had a witnessed out‐of‐hospital cardiac arrest, 27% had in‐hospital cardiac arrest, and 9% were under active cardiopulmonary resuscitation during MCS implantation. Patients presented with a mean systolic blood pressure of 77.2±19.2 mm Hg, 85% of patients were on vasopressors or inotropes, mean lactate was 4.8±3.9 mmol/L and cardiac power output was 0.67±0.29 watts. At 24 hours, mean systolic blood pressure improved to 103.9±17.8 mm Hg, lactate to 2.7±2.8 mmol/L, and cardiac power output to 1.0±1.3 watts. Procedural survival, survival to discharge, survival to 30 days, and survival to 1 year were 99%, 71%, 68%, and 53%, respectively. Conclusions Early use of MCS in AMI‐CS is feasible across varying health care settings and resulted in improvements to early hemodynamics and perfusion. Survival rates to hospital discharge were high. Given the encouraging results from our analysis, randomized clinical trials are warranted to assess the role of utilizing early MCS, using a standardized, multidisciplinary approach.

Khista Rahman,1 Gowhar Ali,1,2 Rasool Khan,3 Imad Khan,3 Izaz Ali,1 Osama F Mosa,4,5 Alshebli Ahmed,4,6 Muhammad Ayaz,7 Asif Nawaz,7 HC Ananda Murthy8 1Department of Pharmacy, University of Peshawar, Peshawar, Pakistan; 2The Ken and Ruth Davee Department of Neurology, Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 3Institute of Chemistry Sciences, University of Peshawar, Peshawar, Pakistan; 4Public Health Department,Health Sciences College at Lieth, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia; 5Biochemistry Department Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan; 6University of Khartoum, Faculty of Public and environmental Health, Khartoum, Sudan; 7Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000, Dir (L), KP, Pakistan; 8Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, EthiopiaCorrespondence: Gowhar Ali; HC Ananda Murthy, Email gowhar_ali@uop.edu.pk; anandkps350@gmail.comPurpose: Gastric ulcer induced by NSAIDs is the major medical concern and researchers are utilizing several approaches to combat this medical issue. In the current study, we investigated the efficacy of thiadiazinethione derivative (2,2’(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid, as new less ulcerogenic compound.Methods: 2,2’(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid was evaluated using standard animal models including hot plate, writhing test and formalin induced nociceptive models. Anti-inflammatory activity was assessed via carrageenan-induced paw oedema model. Involvement of opioidergic nociceptive mechanism was confirmed via naloxone administration in hot plat assay. The gastro-ulcerogenic potential of test and standard compounds were evaluated via NSAID-induced pyloric ligation model followed by standard histopathological and biochemical analysis.Results: In acetic acid-induced writhing test, our compound significantly reduced abdominal constrictions at the tested doses of 15 (p < 0.05), 30 (p < 0.01) and 45 mg kg− 1 (p < 0.001) as compared to control (p < 0.001). In hot plate test, after 30 min of administration, our test compound showed significant anti-nociceptive potential (p < 0.05 at 15 and 30 mg kg− 1 and p < 0.01 at 45 mg kg− 1) and tramadol (p ˂ 0.001) at 30 mg kg− 1 dose. After 60 min tramadol (30 kg− 1) and test sample (30, 45 mg kg− 1) exhibited significant anti-nociceptive activity p < 0.001. In Formalin-induced nociceptive response, a significant decline (p ˂ 0.001) was observed for aspirin and test compound during acute and chronic phases. Decline in the anti-nociceptive potential of tramadol and test sample via administration of naloxone indicate the involvement of opioidergic mechanism. Our compound exhibited significant anti-inflammatory activity in second phase of carrageenan induced paw oedema model. Histological and biochemical parameters exhibited less ulcerogenic potential as compared to aspirin.Conclusion: Our findings suggests that our test compound has desirable anti-nociceptive and anti-inflammatory potentials with less propensity to cause gastric ulcer.Keywords: NSAIDs, nociception, inflammation, gastric ulcer, hot plate

Sajjad Ahmad,1 Mater H Mahnashi,2 Bandar A Alyami,2 Yahya S Alqahtani,2 Farhat Ullah,1 Muhammad Ayaz,1 Muhammad Tariq,3 Abdul Sadiq,1 Umer Rashid4 1Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Khyber Pakhtunkhwa, Pakistan; 2Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia; 3Department PCB, Rokhan University, Jalalabad, Nangrahar, Afghanistan; 4Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, PakistanCorrespondence: Abdul SadiqDepartment of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), Khyber Pakhtunkhwa, PakistanTel +92 301 2297 102Email sadiquom@yahoo.comUmer RashidDepartment of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, PakistanTel +92-334 5171999Email umerrashid@cuiatd.edu.pkBackground: Organocatalytic asymmetric Michael addition is a strong approach for C-C bond formation. The objective of the study is to design molecules by exploiting the efficiency of Michael Adducts. We proceeded with the synthesis of Michael adducts by tailoring the substitution pattern on maleimide and trans-β-nitro styrene as Michael acceptors. The synthesized compounds were evaluated for dual cyclooxygenases (COX) and lipoxygenase (LOX) inhibition.Methods: The compounds (4, 9– 11) were synthesized through Michael additions. The cyclooxygenases (COX-1 and 2) and lipoxygenase (5-LOX) assays were used for in vitro evaluations of compounds. After the acute toxicity studies, the in vivo analgesic potential was determined with acetic acid induced writhing, tail immersion, and formalin tests. Furthermore, the possible roles of adrenergic and dopaminergic receptors were also studied. Extensive computational studies were performed to get a better understanding regarding the binding of this compound with protein target.Results: Four Michael adducts (4, 9– 11) were synthesized. Compound 4 was obtained in enantio- and diastereopure form. The stereopure compound 4 showed encouraging COX-1 and-2 inhibitions with IC50 values of 128 and 65 μM with SI of 1.94. Benzyl derivative 11 showed excellent COX-2 inhibition with the IC50 value of 5.79 μM and SI value 7.96. Compounds 4 and 11 showed good results in in vivo models of analgesia like acetic acid test, tail immersion, and formalin tests. Our compounds were not active in dopaminergic and adrenergic pathways and so were acting centrally. Through extensive computational studies, we computed binding energies, and pharmacokinetic predictions.Conclusion: Our findings conclude that our synthesized Michael products (pyrrolidinedione 4 and nitroalkane 11) can be potent centrally acting analgesics. Our in silico predictions suggested that the compounds have excellent pharmacokinetic properties. It is concluded here that dual inhibition of COX/LOX pathways provides a convincing step towards the discovery of safe lead analgesic molecules.Keywords: Michael products, succinimides, cyclooxygenase, lipoxygenase, analgesic, molecular docking, adrenergic and dopaminergic

Ashfaq Ahmad,1,2 Farhat Ullah,2 Abdul Sadiq,2 Muhammad Ayaz,2 Muhammad Saeed Jan,2 Muhammad Shahid,2 Abdul Wadood,3 Fawad Mahmood,2 Umer Rashid,4 Riaz Ullah,5 Muhammad Umar Khayam Sahibzada,1 Ali S Alqahtani,5 Hafiz Majid Mahmood6 1Department of Pharmacy, Sarhad University of Science & Technology, Peshawar, KPK, Pakistan; 2Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000, KP, Pakistan; 3Department of Biochemistry, UCS, Shankar Abdul Wali Khan University, Mardan 23200, Pakistan; 4Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan; 5Department of Pharmacognosy, Medicinal, Aromatic and Poisonous Plants Research Center (MAPRC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 6Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCorrespondence: Abdul SadiqDepartment of Pharmacy,Faculty of Biological Sciences, University of Malakand, Chakdara 18000, KP, PakistanTel +92 301-2297-102Email sadiquom@yahoo.comAshfaq AhmadDepartment of Pharmacy, Sarhad University of Information Technology, Peshawar, PakistanEmail ashfaqpharma123@gmail.comIntroduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays.Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver–Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis–Menten kinetics.Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 μM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 μM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 μM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 μM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2.Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.Keywords: succinimides, Alzheimer’s disease, cholinesterase, antioxidant, glucosidase, molecular docking

Sajid Hussain,1,2 Farhat Ullah,1 Muhammad Ayaz,1 Syed Adnan Ali Shah,3 Azhar-ul-Haq Ali Shah,4 Syed Majid Shah,1,2 Abdul Wadood,5 Waqar Aman,2 Riaz Ullah,6 Abdelaaty A Shahat,6,7 Fahd A Nasr6 1Department of Pharmacy, University of Malakand, Malakand, Pakistan; 2Department of Pharmacy, Kohat University of Science & Technology, Kohat, Pakistan; 3Research Institute of Natural Products for Drug Discovery (RiND), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Shah Alam, Malaysia; 4Department of Chemistry, Kohat University of Science & Technology, Kohat, Pakistan; 5Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, Pakistan; 6Department of Pharmacognosy (Medicinal Aromatic and Poisonous Plants Research Center), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 7Chemistry of Medicinal Plants Department, National Research Centre, Dokki, Giza, EgyptCorrespondence: Sajid Hussain; Farhat UllahDepartment of Pharmacy, University of Malakand, Dir (L), Chakdara 18000, KPK, PakistanTel +92 3339178183; +92 3339361513Email hussain77pk2003@yahoo.com; farhataziz80@hotmail.comBackground: Cancer is one of the chronic health conditions worldwide. Various therapeutically active compounds from medicinal plants were the current focus of this research in order to uncover a treatment regimen for cancer. Anchusa arvensis (A. anchusa) (L.) M.Bieb. contains many biologically active compounds.Methods: In the current study, new ester 3-hydroxyoctyl -5- trans-docosenoate (compound-1) was isolated from the chloroform soluble fraction of A. anchusa using column chromatography. Using MTT assay, the anticancer effect of the compound was determined in human hepatocellular carcinoma cells (HepG-2) compared with normal epithelial cell line (Vero). DPPH and ABTS radical scavenging assays were performed to assess the antioxidant potential. The Molecular Operating Environment (MOE-2016) tool was used against tyrosine kinase.Results: The structure of the compound was elucidated based on IR, EI, and NMR spectroscopy technique. It exhibited a considerable cytotoxic effect against HepG-2 cell lines with IC50 value of 6.50 ± 0.70 μg/mL in comparison to positive control (doxorubicin) which showed IC50 value of 1.3±0.21 μg/mL. The compound did not show a cytotoxic effect against normal epithelial cell line (Vero). The compound also exhibited significant DPHH scavenging ability with IC50 value of 12 ± 0.80 μg/mL, whereas ascorbic acid, used as positive control, demonstrated activity with IC50 = 05 ± 0.15 μg/mL. Similarly, it showed ABTS radical scavenging ability (IC50 = 130 ± 0.20 μg/mL) compared with the value obtained for ascorbic acid (06 ± 0.85 μg/mL). In docking studies using MOE-2016 tool, it was observed that compound-1 was highly bound to tyrosine kinase by having two hydrogen bonds at the hinge region. This good bonding network by the compound might be one of the reasons for showing significant activity against this enzyme.Conclusion: Our findings led to the isolation of a new compound from A. anchusa which has significant cytotoxic activity against HepG-2 cell lines with marked antioxidant potential.Keywords: cancer, Anchusa arvensis, 3-hydroxyoctyl-5, trans-docosenoate, cytotoxicity against HepG-2 cell lines, antioxidant

Ashfaq Ahmad,1 Farhat Ullah,1 Abdul Sadiq,1 Muhammad Ayaz,1 Haroon Rahim,2 Umer Rashid,3 Sajjad Ahmad,1 Muhammad Saeed Jan,1 Riaz Ullah,4 Abdelaat A Shahat,4,5 Hafiz Majid Mahmood6 1Department of Pharmacy, University of Malakand, Chakdara, Dir (L), KP (Khyber Pakhtunkhwa) 18000, Pakistan; 2Department of Pharmacy, Sarhad University of Science & Information Technology, Peshawar, KP (Khyber Pakhtunkhwa), Pakistan; 3Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, KP (Khyber Pakhtunkhwa), Pakistan; 4Department of Pharmacognosy (MAPPRC), College of Pharmacy, King Saud University Riyadh, Riyadh, Saudi Arabia; 5Phytochemistry Department, National Research Centre, Giza, Egypt; 6Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCorrespondence: Haroon Rahim; Abdul SadiqDepartment of Pharmacy, Sarhad University of Science and Information Technology Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan; Department of Pharmacy, University of Malakand Khyber Pakhtunkhwa, Chakdara 18800, PakistanTel +92-3329461642; +92-301-2297102Email hrahimpk@gmail.com, sadiquom@yahoo.comPurpose: The current work was designed to synthesize a bioactive derivative of succinimide and evaluate it for anti-Alzheimer, anticancer and anti-diabetic potentials.Methods: The compound was synthesized by Michael addition of butyraldehyde with N-phenylmaleimide. The synthesized compound was screened for biological potentials including anti-cholinesterase, in-vitro anti-diabetic, antioxidant and anthelmintic potentials. The anti-cholinesterase potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), anti-diabetic potential against α-glucosidase, antioxidant potential against ABTS, DPPH and H2O2 and anthelmintic potential against Perethima posthuma and Ascaridia galli respectively.Results: The compound demonstrated significant AChE and BChE inhibition i.e., 71.34±1.92 and 73.42 ±1.92 at the concentration of 1000 μg/mL respectively. Other dilutions exhibited concentration-dependent inhibitory activity against both enzymes. In the MTT assay, the newly synthesized compound was found active against all of the cell lines viz, HCT-116, MDA-MB231, NIH/3T3 and MCF-7 and the highest cytotoxicity potential was observed against the colon cancer cell line (HCT-116) with an IC50 value of 78 μg/mL exhibiting its highest potential. Moreover, the compound exhibited prominent α-glucosidase inhibitory potentials (79.86±2.54% at 1000 μg/mL) with IC50 value of 156.23 μg/mL. Further, our test compound exhibited considerable scavenging activity against DPPH, ABTS and H2O2 free radicals with percent inhibitions of 75.84±1.58, 72.85±1.17 and 54.82±1.82 and IC50 values of 84.36, 139.74 and 752.21 μg/mL respectively. Our test sample exhibited significant anthelmintic potentials. It demonstrated significant paralysis and death of the test worms in an unbelievably short time in comparison with albendazole.Conclusion: Going into the detail of all observations, it may be deduced that the newly synthesized succinimide derivative could be an important drug candidate against neurodegenerative disorders like Alzheimer’s disease, cancer, diabetes mellitus and worms. Further detailed studies in animal models are required for in-vivo analysis of the compound.Keywords: Succinimide, Alzheimer’s disease, MTT, oxidative stress, diabetes, helminthiasis

Autosomal recessive peripheral neuropathy with neuromyotonia (ARAN-NM) is a relatively newly described disease associated with mutations in the HINT1 gene. It accounts for a significant part of the poorly differentiated forms of axonal polyneuropathies. We present the first in Russia description of the genetically confirmed case of ARAN-NM in a boy aged 14 years and 11 months without the hereditary-tainted anamnesis. On presentation, the patient experienced progressive distal muscular weakness, asymmetric foot deformity, gait disorders and minimal manifestations of neuromyotonia (stiffness in the fingers). During examination, we detected an increase in the level of creatine phosphokinase up to 635 U/l, a disturbance of conduction of motor and, to a lesser extent, sensory fibers of the peripheral nerves (according to the stimulation electromyography, EMG), denervation-reinnervation changes, single positive acute waves, fibrillation potentials, complex repeated discharge (according to the data of needle EMG). In the study of exome, a homozygous mutation c.110G>C, p.R37P was determined in exon 01 of the HINT1 gene, which confirmed the presence of ARAN-NM. A molecular-genetic examination of the patient's immediate relatives was carried out. The described case is compared with literature data. An overview of currently available information on ARAN-NM is provided. Diagnostic criteria of the disease are presented.

The botulinum therapy remains the most effective and safe method for reducing local spasticity in patients with cerebral palsy (CP). However, the list of indications for injections of botulinum toxin type A (BTA) in cerebral palsy is limited both in terms of target muscles and the treatment initiation age. In this regard, doctors are guided by the data of clinical studies, reviews and consensuses of experts, which are advisory in nature. One of the most urgent issues in the modern CP botulinum therapy is the evaluation of risks andbenefits of initiating injections at an early age (up to 2 years) in order to prevent orthopedic complications and stimulate the optimal motor development of a child. The review analyzes the history of the development of modern approaches to the use of botulinum therapy in cerebral palsy and the tactics of selecting target muscles and doses for multilevel injections. The authors focus on the latest international data on the feasibility and safety of reducing the admissible initiation age for botulinum therapy in cerebral palsy. The results from the studies of the effect of the early initiation of BTA injections on motor development, formation of secondary orthopedic complications in children under 2 years of age, and morphological changes in the neuromotor apparatus in animal experiments are presented. The concept of «key muscles» is considered in detail as one of the possible reference points in the planning of safe andeffective early injections.

The increase in industrialization has led to an exponential increase in heavy metal (HM) soil contamination, which poses a serious threat to public health and ecosystem stability. This review emphasizes the urgent need to develop innovative technologies for the environmental remediation of intensive anthropogenic pollution. Phytoremediation is a sustainable and cost-effective approach for the detoxification of contaminated soils using various plant species. This review discusses in detail the basic principles of phytoremediation and emphasizes its ecological advantages over other methods for cleaning contaminated areas and its technical viability. Much attention has been given to the selection of hyperaccumulator plants for phytoremediation that can grow on heavy metal-contaminated soils, and the biochemical mechanisms that allow these plants to isolate, detoxify, and accumulate heavy metals are discussed in detail. The novelty of our study lies in reviewing the mechanisms of plant–microorganism interactions that greatly enhance the efficiency of phytoremediation as well as in discussing genetic modifications that could revolutionize the cleanup of contaminated soils. Moreover, this manuscript discusses potential applications of phytoremediation beyond soil detoxification, including its role in bioenergy production and biodiversity restoration in degraded habitats. This review concludes by listing the serious problems that result from anthropogenic environmental pollution that future generations still need to overcome and suggests promising research directions in which the integration of nano- and biotechnology will play an important role in enhancing the effectiveness of phytoremediation. These contributions are critical for environmental scientists, policy makers, and practitioners seeking to utilize phytoremediation to maintain the ecological stability of the environment and its restoration. [ABSTRACT FROM AUTHOR]