Animal Placental Therapy: An emerging tool for Health Care.

Background: The placenta maintains and regulates the growth of foetus and consists of various biologically active nutrients such as cytomedines, vitamins, trace elements, amino acids, peptides, growth factors and other biologically active constituents. Introduction: The therapeutic effectiveness of the placenta can be well defined with respect to several biochemical mechanisms of various components present in it. The placental extract derived from biomedical wastes has also shown a great potential for treatment of various diseases. Method: Placental therapy has been reported specifically to have potent action on treatment of diseases and tissue regeneration. Result: Placental bioactive components and their multi-targeting identity prompted us to compile the précised information on placental extract products. However, some findings are needed to be explored by scientific community to prove their clinical potential with significant statistical validation. Conclusion: In the light of available information and the usefulness of the placental extract, it is necessary that the formulations of various desirable properties may be developed to meet the clinical requirements in several treatment paradigms. It is also a matter of exploration that the short- and long-term adverse effects to be explored by advanced scientific techniques.

Adaptive griffiths scale − modern experience in assessing the psychomotor development of preschool children

Premature newborns build a specific category of children due to their innate morpho-functional immaturity and specific pathological conditions that determine significant survival, morbidity and postnatal care results as compared to children of other weight categories. In the long-term adverse effects of preterm birth, the incidence of neuropathy remains high and requires further improvements in diagnostic methods and timely corrections for a better developmental prognosis. Although over the past three decades, numerous tools have been invented to predict long-term adverse effects of preterm neonates as well as methods for determining degree of disorders, neither these tools nor their weak and strong points have undergone a comprehensive overview. Aim of the research was to improve long-term preterm birth outcomes by using the adaptive Griffiths scale for preschoolers. The psychomotor development of 105 preschoolers was evaluated. Assessment of indicators of psychomotor development was carried out by the adaptive Griffiths scale and the conventional method. In the course of the study, this category of children was under doctors' from Neonates Post-discharge Follow-ups Department with systematic evaluation of their health condition. Dynamic examination was performed during the first year of life once per 3 months, from the 2nd to the 6th year of life – corresponding to an individual rehabilitation plan. Patients (n=105) were divided into 3 groups depending on the severity of the disabling pathology. The analysis of indicators of psychomotor development (by traditional methods) of prematurely born preschoolers, divided into 3 groups in accordance with severity degree of disabling pathology: Group A children with severe long-term consequences that led to disability – 54 (51.4%) Group B. Children with long – term consequences who are subject to correction - 24 (22.8%) Group C. Children with long-term consequences not significantly affecting their health condition -27 (25.7%). The conducted survey suggests, that above 70% of the children had various patterns of delayed psychomotor development. The assessment of psychomotor development showed that the cause structure of delayed psychomotor development of preschoolers has the same trend according to different examination methods, but the assessment by the adaptive Griffiths scale shows more accurate values for each patient, enables quick detection of long-term adverse consequences of premature birth, recommendations for parents for neonates' rehabilitation and habilitation, as well as examination in dynamics. In the flow of the research, the adaptive Griffiths scale of psychomotor development proved to be a valid diagnostic tool for determining indicators of preschoolers' psychomotor development, estimating their intellectual coefficient and forming individual patient's profile.

Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.

Alcohol-abuse drug disulfiram targets pediatric glioma via MLL degradation

Pediatric gliomas comprise a broad range of brain tumors derived from glial cells. While high-grade gliomas are often resistant to therapy and associated with a poor outcome, children with low-grade gliomas face a better prognosis. However, the treatment of low-grade gliomas is often associated with severe long-term adverse effects. This shows that there is a strong need for improved treatment approaches. Here, we highlight the potential for repurposing disulfiram to treat pediatric gliomas. Disulfiram is a drug used to support the treatment of chronic alcoholism and was found to be effective against diverse cancer types in preclinical studies. Our results show that disulfiram efficiently kills pediatric glioma cell lines as well as patient-derived glioma stem cells. We propose a novel mechanism of action to explain disulfiram’s anti-oncogenic activities by providing evidence that disulfiram induces the degradation of the oncoprotein MLL. Our results further reveal that disulfiram treatment and MLL downregulation induce similar responses at the level of histone modifications and gene expression, further strengthening that MLL is a key target of the drug and explaining its anti-oncogenic properties.

Remission of Recalcitrant Psoriasis on Combined Biologic Therapy With Infliximab and Ustekinumab

Introduction: Anti-TNF treatment is effective for inflammatory bowel disease (IBD), however it also has the potential to cause paradoxical psoriasis which can be challenging to manage. Discontinuation of anti-TNF agents may improve psoriatic lesions but may worsen IBD. Combining biologic therapies, though not yet commonly practiced, may be a useful approach to the treatment of both conditions. Case Presentation: We describe a case of paradoxical palmoplantar psoriasis in a 48-year-old woman with ulcerative colitis (UC). Her UC was well-managed on infliximab. Following trials of several other topical and systemic therapies for her psoriatic lesions, she ultimately received relief on combined ustekinumab and infliximab therapy without flare of her IBD. Discussion: While other publications report success using ustekinumab for paradoxical psoriasis following cessation of infliximab, this case report highlights successful treatment using a combination of ustekinumab and infliximab with no reported adverse effects at 3 months. Conclusion: Discontinuation of the anti-TNF agent and use of a single biologic that may treat both IBD and psoriasis is a treatment option. Additionally, combining biologic therapies, though not yet commonly practiced, may be a useful, albeit costly, approach to prevent potential flares of IBD that may accompany cessation of some biologics. Further studies may be beneficial to assess for long term adverse effects.

Biologicals in Atopic Dermatitis

Atopic dermatitis (AD) is a debilitating condition, and its management in both children and adults can be challenging for clinicians and patients alike. The current treatment options approved by the Food and Drug Administration (FDA) have variable efficacies, and long-term adverse effects, which further complicate the plan of management. There has been considerable progress towards the use of targeted medicines like biologicals and small molecular agents for atopic dermatitis. Various molecules targeting the TH2 pathway, JAK/STAT pathway, cAMP, IL-22, Il-12/IL-23 and IgE, have been developed, and are being studied extensively in both adults and pediatric patients of atopic dermatitis. Currently, only Dupilumab is approved by the FDA for the treatment of moderate to severe refractory atopic dermatitis. The other biological agents are currently in phase 2 or phase 3 trials. There is a paucity of multicentric, large-scale studies on the above drugs, along with a lack of comparative studies with the existing modalities of treatment. Therefore, more studies with a larger sample size and longer follow up periods are needed to determine their efficacy and long-term safety profiles. Overall, these agents are likely to be a part of the therapeutic armamentarium for atopic dermatitis in the near future.

UV Stimulated Manganese Dioxide for the Persulfate Catalytic Degradation of Bisphenol A

One of the most commonly produced industrial chemicals worldwide, bisphenol A (BPA), is used as a precursor in plastics, resins, paints, and many other materials. It has been proved that BPA can cause long-term adverse effects on ecosystems and human health due to its toxicity as an endocrine disruptor. In this study, we developed an integrated MnO2/UV/persulfate (PS) process for use in BPA photocatalytic degradation from water and examined the reaction mechanisms, degradation pathways, and toxicity reduction. Comparative tests using MnO2, PS, UV, UV/MnO2, MnO2/PS, and UV/PS processes were conducted under the same conditions to investigate the mechanism of BPA catalytic degradation by the proposed MnO2/UV/PS process. The best performance was observed in the MnO2/UV/PS process in which BPA was completely removed in 30 min with a reduction rate of over 90% for total organic carbon after 2 h. This process also showed a stable removal efficiency with a large variation of pH levels (3.6 to 10.0). Kinetic analysis suggested that 1O2 and SO4•− played more critical roles than •OH for BPA degradation. Infrared spectra showed that UV irradiation could stimulate the generation of –OH groups on the MnO2 photocatalyst surface, facilitating the PS catalytic degradation of BPA in this process. The degradation pathways were further proposed in five steps, and thirteen intermediates were identified by gas chromatography-mass spectrometry. The acute toxicity was analyzed during the treatment, showing a slight increase (by 3.3%) in the first 30 min and then a decrease by four-fold over 2 h. These findings help elucidate the mechanism and pathways of BPA degradation and provide an effective PS catalytic strategy.

Review of COVID-19 Vaccines and the Risk of Chronic Adverse Events Including Neurological Degeneration

Many have argued that the outbreak of COVID-19 is the result of the release of a viral based bioweapon. Vaccines to COVID-19 have been developed and a policy of universal immunization has been initiated with total disregard to the fact that the virus may be a bioweapon. The potential risk of a catastrophe exists in part because all the vaccines contain the spike protein and or the mRNA/DNA encoding for the COVID-19 associated spike protein. These vaccines were designed and placed on the market with little knowledge of how the spike protein or its nucleic acid causes disease and without knowledge of long-term adverse effects of the vaccines. This paper reviews many of the potential long-term risks that could result from receiving one of the COVID-19 vaccines. The potential for the spike protein and its mRNA to cause prion disease is reviewed as well as reasons why the vaccine could be much more dangerous than the natural infection. Adenoviral derived COVID-19 vaccines are particularly risky because of their potential to recombine with human DNA or viruses already in the human recipient. The result could be new infectious adenoviral species containing spike proteins that could infect humans and farm animals used for food. Some of the COVID-19 vaccines utilize novel technology including nanotechnology and novel adjuvants that increase intracellular penetration of cells and can potentially exacerbate chronic toxicity from the spike protein. Governments should consider suspending sale of the COVID-19 vaccines until they have a better understanding of their risks.