Possible mechanism of central nervous system targeting and neurological symptoms of the new-coronavirus (COVID-19): literature review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the 2019 Coronavirus Disease (COVID-19) has been associated with several neurological symptoms. This review aimed to highlight the possible mechanism of central nervous system (CNS) targeting and the neurological symptoms that may occur with the COVID-19 infection. The case reports containing the keywords "neurological symptoms" and "COVID-19" were thoroughly reviewed to identify possible mechanisms of CNS targeting and neurological manifestations associated with COVID-19 infection. The angiotensin-converting enzyme-2 (ACE2) receptors have been identified as the functional receptor for SARS-CoV-2. SARS-CoV-2 can affect the CNS through the following mechanisms: 1) Direct infection. 2) Blood pathway. 3) Neuronal pathway. 4) Immune-mediated injury/pathway (Cytokine Storm Syndrome). COVID-19 virus, a neurotropic virus, was isolated from the cerebral fluid (CSF) and responsible for several neurological manifestations. The COVID-19 infection primarily affects CD4+ and CD8+ T-lymphocytes and it induces a surge of inflammatory cytokines, known as Cytokine Storm Syndrome (CSS). The Interlukine-6 (IL-6) is the primary CSS component. The IL-6, interferon-γ and endothelial growth factor were significantly higher in COVID-19 infected compared to non-infected individuals. The improvement of the COVID-19 patients after interleukin receptor blockers supports the CSS theory. The spectrum of SARS-CoV-2 neurological manifestations includes encephalitis, viral meningitis, post-COVID-19 infectious acute disseminated encephalitis, Guillain-Barré Syndrome (GBS), Miller-Fisher syndrome (MFS) and acute cerebrovascular disease (CVD). Several COVID-19-associated neurological manifestations have been reported. Thus, it is important to identify and treat neurological symptoms as soon as possible to avoid long-term effects. The care providers should take the appropriate preventive precautions because patients can present with neurological manifestations of COVID-19 without any respiratory symptoms. Future research is warranted to confirm the relationship between SARS-CoV-2 and the development of neurological manifestations.

The cortisol levels in the follicular and luteal phases of the healthy menstruating women: a meta-analysis.

OBJECTIVE: The conflicting results of the previous studies regarding the serum cortisol through the menstrual cycle warranted further research. We aimed to detect the cortisol levels in the follicular and luteal phases of healthy menstruating women. MATERIALS AND METHODS: A literature search was conducted by two independent authors according to PRISMA criteria over PubMed, Web of Science and Psych-Info to retrieve the articles published in English from 1990 until 2020 and containing the keywords, Cortisol, Menstrual, Follicular, or Luteal. The quality assessment of the articles/studies was done using the CONSORT and STROBE checklists. The risk bias was assessed by two independent authors using Cochrane risk-bias assessment tool. RESULTS: Twenty-eight (28) articles were included in this meta-analysis. The cortisol levels were significantly higher in the studied-participants' follicular phase compared to the luteal phase (p<0.01). The cortisol levels sub-analysis showed a significant effect of plasma cortisol over the salivary cortisol (p=0.04). The cortisol assay time showed a significant effect of the morning cortisol over the afternoon cortisol (p=0.005). CONCLUSIONS: This meta-analysis found the cortisol levels were significantly higher in the studied-participants follicular phase compared to the luteal phase. The cortisol sub-analysis showed a significant effect of plasma and morning cortisol over the salivary and afternoon cortisol, respectively.

The γ-H2AX foci as an indicator for double-stranded DNA breaks and response to ongoing chemotherapy in breast cancer women: a pilot study.

OBJECTIVE: The double-stranded breaks (DSBs) of the DNA can predispose to cancer development. The γH2AX foci have been proposed for prediction of tumor growth and response to radiotherapy. We aimed to evaluate the γ-H2AX foci as an indicator for DSBs and response to ongoing chemotherapy in breast cancer women. PATIENTS AND METHODS: Twenty-nine (29) breast cancer women, scheduled for adjuvant chemotherapy were included in this pilot study after obtaining written informed consent and approval of the study by the WKMU ethics committee. Participants received adjuvant chemotherapy, according to the treatment protocol of the Republic of Kazakhstan. A peripheral blood sample was collected from each studied participant for analysis of the γ-H2AX foci in the participants' lymphocytes using the immunofluorescent staining kit. Data of the Fluorescein isothiocyanate (FITC) rupture, and Adenomatous Polyposis Coli (APC) repair channels were analyzed to evaluate the γ-H2AX foci as an indicator for DSBs, and response to ongoing chemotherapy. RESULTS: About 10.3% (3/29) of the studied breast cancers were luminal A, 72.4% (21/29) were luminal type B, 13.8% (4/29) were basal-like, and 3.5 (1/29) were HER2 positive. The FITC rupture channel during the ongoing chemotherapy showed significantly decreased foci intensity means (p=0.0075), and significantly increased colocalization (p=0.02). The APC repair channels during the ongoing chemotherapy showed significantly increased nuclei intensity (p=0.046), foci overall (p=0.0007), clusters (p=0.002), foci mean (p<0.0001), and foci mean + clusters (p=0.0003). It also showed significantly increased clusters positive cells (p<0.0001), foci low intensity (p<0.0001), foci low intensity + clusters (p=0.0003), and clusters of low-intensity positive cells (p=0.002). CONCLUSIONS: The γ-H2AX foci, the changes in the FITC rupture, and APC repair channels can serve as real-time indicators for the response to ongoing chemotherapy in breast cancer women. The γ-H2AX foci as an indicator for DSBs/repair pathway, and for the response to ongoing chemotherapy in breast cancer should be evaluated in further studies.

The relation between vitamin D and the adolescents' mid-luteal estradiol and progesterone.

OBJECTIVE: The aim of this study was to detect the effect of vitamin D (Vit. D) intake on the mid-luteal estradiol (E2), and progesterone (P), and the relation between vit. D, and the adolescents' mid-luteal E2, and P. PATIENTS AND METHODS: Eighty-five (85) adolescents were recruited for this cohort study after obtaining informed consent. After a detailed history and clinical examination, the body mass index (BMI) of the studied participants was calculated, followed by pelvic sonography to exclude any pelvic pathology. Participants' blood samples were collected on days 21-22 of the menstrual cycle (mid-luteal) to measure the thyrotropin (TSH) (i.e., to exclude hypothyroidism), prolactin (i.e., to exclude hyperprolactinemia), glycosylated hemoglobin (HbA1C), (i.e., to exclude diabetes), E2, P, and 25(OH)D.  Participants received 50,000 IU of vit. D weekly for two months, and on the 3rd month, the mid-luteal E2, P, and 25(OH)D were measured. The mid-luteal E2, P, and 25(OH)D were compared before and after the vit. D intake to detect the effect of vit. D intake (50,000 IU weekly for 2 months) on the mid-luteal E2 and P (primary outcome). Additionally, the relations between vit. D and the adolescents' mid-luteal E2 and P were detected as secondary outcomes using the correlation analysis (Pearson's correlation). RESULTS: The mid-luteal E2 and P statistically decreased from 109.3±15.7 pg/mL and 9.8±1.01 ng/mL, respectively to 40.7±10.52 pg/mL, and 5.2±0.73 ng/mL, respectively, after vit. D intake (p=0.00015; 95% CI: 64.5, 68.6, 72.7, and p=0.0016; 95% CI: 4.3, 4.6, 4.87, respectively). Significant negative correlations between the 25(OH)D, and both the mid-luteal E2 (r -0.661; p<0.00001), and P (r -0.521; p<0.00001) were detected in this study. CONCLUSIONS: The mid-luteal E2 and P statistically decreased after vit. D intake (50,000 IU of vit. D weekly for 2 months). Significant negative correlations between the 25(OH)D, and both the mid-luteal E2 and P were detected in this study. The relation between vit. D and ovarian steroids, and the effect of vit. D intake on ovarian steroids need further larger studies.

АIR POLLUTION EMISSIONS ARE ASSOCIATED WITH INCIDENCE AND PREVALENCE OF BREAST CANCER IN THE AKTOBE REGION OF WESTERN KAZAKHSTAN.

Purpose - to establish a relationship between the incidence and the prevalence of breast cancer and air emissions of pollutants in the Aktobe region of the Republic of Kazakhstan.A retrospective study of the database was carried out on the territory of the Aktobe region of Western Kazakhstan. The data were obtained from the Register of Oncological Diseases of the Aktobe Regional Cancer Center. Data on air emissions for 2014-2019 were obtained from the Annual Statistical Bulletin "Environmental statistics. On the state of protection of atmospheric air in Kazakhstan" of the Committee on Statistics of the Republic of Kazakhstan.Breast cancer ranks is first among the malignant oncological pathology of women in the Aktobe region in 2019 and is 20.5% (95% CI 19.6-21.4) of all cancer cases. The analysis shows that the incidence and prevalence of breast cancer in 2014-2019 continues to grow: incidents from 37.3 (2014) to 56.0 (2019) per 100,000 population, the growth rate is 8.3%; prevalence: from 274.0 (2014) to 344.8 (2019) per 100,000 population, the growth rate is 4.7%. Spearman's rank correlation analysis showed a strong direct relationship between benzene emissions and the incidence (r=0.8, p=0.027). A direct strong relationship was found between the prevalence of breast cancer and the amount of emissions into the atmosphere (r=0.8, p=0.027), carbon monoxide (r=0.9, p=0.037), nitrogen oxides (r=0.9, p=0.037), lead (r=0.8, p=0.021), hexavalent chromium (r=0.6, p=0.048), xylene (r=0.7, p=0.047), toluene (r=0.8, p=0.034), methanol (r=0.8, p=0.040), butyl acetate (r=0.7, p=0.046).The unfavorable environmental situation in the Aktobe region associated with the release of chemical pollutants and heavy metals can contribute to the development of cancer. The revealed correlation between the prevalence of breast cancer and the release of chemical elements into the atmosphere requires further study to determine risk factors for breast cancer in the region of Western Kazakhstan.