Although CDK7 inhibitors are considered to be potential anticancer drugs, all inhibitors developed so far have significant disadvantages preventing their further use. We have developed a new CDK7 inhibitor scaffold lacking hepatotoxicity using molecular dynamics (MD) and free energy perturbation (FEP/MD) methods, and were able to double its binding affinity after additional research. The combination of MD and FEP/MD methods was shown to be a valuable instrument for the development of novel and potent CDK7 inhibitors for anticancer therapy.
Previously, a consolidated mathematical model of primary tumor (PT) growth and secondary distant metastasis (sdMTS) growth in breast cancer (BC) (CoMPaS) was presented. The aim was to detect the diagnostic periods for visible sdMTS via CoMPaS in patients with different subtypes ER/PR/HER2/Ki-67 (Estrogen Receptor/Progesterone Receptor/Human Epidermal growth factor Receptor 2/Ki-67 marker) of breast cancer. CoMPaS is based on an exponential growth model and complementing formulas, and the model corresponds to the tumor-node-metastasis (TNM) staging system and BC subtypes (ER/PR/HER2/Ki-67). The CoMPaS model reflects (1) the subtypes of BC, such as ER/PR/HER2/Ki-67, and (2) the growth processes of the PT and sdMTSs in BC patients without or with lymph node metastases (MTSs) in accordance with the eighth edition American Joint Committee on Cancer prognostic staging system for breast cancer. CoMPaS correctly describes the growth of the PT in the ER/PR/HER2/Ki-67 subtypes of BC patients and helps to calculate the different diagnostic periods, depending on the tumor volume doubling time of sdMTS, when sdMTSs might appear. CoMPaS and the corresponding software tool can help (1) to start the early treatment of small sdMTSs in BC patients with different tumor subtypes (ER/PR/HER2/Ki-67), and (2) to consider the patient almost healthy if sdMTSs do not appear during the different diagnostic periods.
Insomnia is one of the most widespread health problems in the general population . It has been estimated that one-third of the general population experience at least one of the insomnia symptoms . According to DSM-5, insomnia is defined as difficulty in initiating or maintaining sleep or early morning awakening accompanied by considerable distress or clinical disturbance . Insomnia is considered as a disorder characterized by nocturnal symptoms (difficulty falling or maintaining asleep) and daytime symptoms (i.e., deterioration in daytime functioning).
The review summarizes studies of chemical and biological processes occurring in human body upon exposure to coronaviruses, in particular SARS-CoV-2. The mechanisms of viral particles penetration into the cell and their replication, impact on the immune system and oxygen transport systems are considered. The mechanisms of complications occurring as a consequence of viral infection - vasculitis, thrombosis, cytokine storm and lung fibrosis are discussed. The review also includes data on the latest research in the field of small molecule medication to counteract the virus. Molecular targets and possible vectors of exploiting them are considered. The review is written primarily for specialists who want to understand the chains of activation, replication, actions and methods of protection/inhibition of SARS-CoV-2. Due to the short period of such studies, the data on complexes of small molecule compounds and possible protein targets are not numerous, but they will be useful in search and synthesis of new potentially effective drugs.
BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.
Prevalence of oral diseases among children is an urgent problem that poses a threat to the health of the growing population in Russia. Dental pathology among children with disabilities has specific characteristics regarding its development, prevalence and intensity of the lesion. Statistically, dental morbidity of children with disabilities is much higher than in somatically healthy. This is due to a number of factors: a slowdown in the perception rate, underdevelopment of the cognitive sphere, violation of behavioral reactions and, as a consequence, inadequate compliance with necessary hygienic procedures. The authors consider that the major etiological factor resulting in the development of diseases of oral mucosa and periodontal condition in patients with neuropsychiatric pathology is absence or poor hygienic care of the oral cavity. The aim of the study is to assess the dental status of children with disabilities and autism spectrum disorders aged 3 – 8 years old. To determine this status, the method of defining and calculating indices reflecting the state of oral tissues was employed. The following indexes were used in the study: Fedorov-Volodkina hygienic index; simplified index of oral hygiene (OHI-S/GAMES-Y),; papillary-marginal-alveolar index (PMA); Index of tooth decay kp, KPU+kp. Dental examination revealed a high prevalence of dental diseases in children with ASD and cerebral palsy; in particular, multiple lesions of hard tissues of the teeth, periodontal inflammation were identified. The findings of the study showed that caries in children with limited abilities is mainly due to their low motivation to develop a habit of individual manual teeth brushing ritual.
Background: Sleep disorders have emerged as potential cancer risk factors.
Objective: This review discusses the relationships between sleep, obesity, and breathing disorders with concomitant risks of developing cancer.
Results: Sleep disorders result in an abnormal expression of clock genes, decreased immunity, and melatonin release disruption. Therefore, these disorders may contribute to cancer development. Moreover, in sleep breathing disorder, which are frequently experienced by the obese persons, the sufferer experiences intermittent hypoxia that may stimulate cancer cell proliferation.
Discussion: During short- or long- duration sleep, sleep-wake rhythm disruption may occur. Insomnia and obstructive sleep apnea increase cancer risks. In short sleepers, an increased risk of stomach cancer, esophageal squamous cell cancer, and breast cancer were observed. Among long sleepers (>9 hours), the risk of some hematologic malignancies is elevated.
Conclusion: Several factors including insomnia, circadian disruption, obesity, and intermittent hypoxia in obstructive sleep apnea are contributing risk factors for increased risk of several types of cancers. However, further studies are needed to determine the more significant of these risk factors and their interactions.
Background: The ability of the human body to produce metabolic energy from light modifies fundamental concepts of biochemistry.
Objective: This review discusses the relationships between the long-accepted concept is that glucose has a unique dual role as an energy source and as the main source of carbon chains that are precursors of all organic matter. The capability of melanin to produce energy challenges this premise.
Results: The prevalent biochemical concept, therefore, needs to be adjusted to incorporate a newly discovered state of Nature based on melanin’s ability to dissociate water to produce energy and to reform water from molecular hydrogen and oxygen.
Discussion: Our findings regarding the potential implication of QIAPI-1 as a melanin precursor that has bioenergetics capabilities.
Conclusion: Specifically, we reported its promising application as a means for treating retinopathy of prematurity (ROP). The instant report focuses on the long-term treatment medical effects of melanin in treating ROP.
Background: In this review we survey medical treatments and research strategies, and we discuss why they have failed to cure degenerative disc diseases or even slow down the degenerative process.
Objective: We seek to stimulate discussion with respect to changing the medical paradigm associated with treatments and research applied to degenerative disc diseases.
Method Proposal: We summarize a Biological Transformation therapy for curing chronic inflammations and degenerative disc diseases, as was previously described in the book Biological Transformations controlled by the Mind Volume 1.
Preliminary Studies: A single-patient case study is presented that documents complete recovery from an advanced lumbar bilateral discopathy and long-term hypertrophic chronic rhinitis by application of the method proposed.
Conclusion: Biological transformations controlled by the mind can be applied by men and women in order to improve their quality of life and cure degenerative disc diseases and chronic inflammations illnesses.