Molecular evolution of SARS-CoV-2 from December 2019 to August 2022

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).     

Clonal karyotypic abnormalities in gynecomastia

Gynecomastia is a benign condition that frequently occurs in the male breast gland; however, the cytogenetic data on this entity are very limited. To our knowledge, three cases have been reported in the literature, and the only one with an abnormal karyotype had a concomitant breast carcinoma. In this study we report clonal chromosomal alterations in a gynecomastia sample without any signs of adjacent malignant tissue. The nonrandom abnormalities observed were a deletion of 12p, monosomies of chromosomes 9, 17, 19, and 20, and the presence of a marker chromosome. Most of these alterations have been previously described in the literature in other breast lesions, including benign and malignant (male and female) tumors, indicating their recurrence and nonrandomness in abnormal processes of the mammary gland.     

Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management.

BACKGROUND: Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy. METHODS: After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4. RESULTS: The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not. CONCLUSIONS: Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.     

Recurrent posttraumatic urethro-vaginal fistula: a new application for ASTRA

The authors describe the results of an application of the surgical technique called ASTRA (anterior sagittal transrectal approach) in a 16-year-old girl with recurrent urethro-vaginal fistula. The young girl had a posttraumatic urethro-vaginal fistula. It recurred after 4 operations by a direct vaginal approach before definitive correction with the ASTRA. Three years after the operation the patient has remained well with complete healing and no fistula recurrence confirmed by a voiding cystourethrogram and urodynamic and rectal manometric tests. This report suggests that ASTRA is a useful method of treating acquired or developmental anomalies of the perineal region.     

Tachykinin NK(3)receptor involvement in anxiety

This study investigates the effects of intracerebroventricular injection of selective agonists and antagonists of tachykinin NK(3)receptor on performance of mice in the elevated plus-maze test. Mice were treated with either vehicle or 1, 10, 100 or 500 pmol of neurokinin B or senktide ([succinil-Asp(6), MePhe(8)]substance P(6-11), a natural and synthetic selective NK(3)receptor agonists, respectively. Other mice received similar doses of [Trp(7)beta-Ala(8)]NKA(4-10)or SR 142801 ((S)-N-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)-piperidin-3-yl)propyl)-4-phenyl-piperidin- 4-yl)-N-m ethylacetamide) tachykinin NK(3)receptor selective peptide and non-peptide antagonists, respectively. Senktide significantly increased the frequency of entries and the time spent in the open arms, which is compatible with an anxiolytic action. Neurokinin B treatment did not alter the plus-maze parameters in a significant way. Conversely, the NK(3)peptide antagonist [Trp(7)beta-Ala(8)]NKA(4-10), but not SR142801 non-peptide antagonist, showed a reverse effect, i.e. an anxiogenic profile of action, reducing the frequency and the time spent in the open arms. Co-injection of either senktide plus [Trp(7)beta-Ala(8)]NKA((4-10)), or senktide plus SR 142801, blocked the effects promoted by senktide, indicating that centrally-administered NK(3)receptor agonists and antagonists can modulate experimental anxiety.     

Facultative control of avian unihemispheric sleep under the risk of predation

Lewis (LEW) is an inbred strain of rats frequently used as an animal model of autoimmune diseases. However, there is evidence that some lines of LEW rats develop autoimmune diseases more readily than do other LEW rat lines. Because the hypothalamus-pituitary-adrenal system is involved in the pathophysiology of these diseases, we compared two LEW lines (SsNHsd and HANRijHsd) in their behavioural and neuroendocrine response to stress. In addition, we studied the psychostimulant effects of acute and repeated amphetamine in these two LEW rat lines. HAN rats were less active in the open field test and showed faster habituation of novelty-induced locomotion. The acoustic startle response was lower in HAN than in SSN rats, whereas prepulse inhibition of the startle response was greater in the HAN than in the SSN LEW subline. Moreover, HAN rats showed impaired acquisition of the two-way active avoidance response relative to SSN rats. The psychostimulant effects of acute amphetamine were smaller in HAN rats. Following repeated injections of amphetamine, behavioural sensitization to the psychostimulant effects of amphetamine was more pronounced in HAN than in SSN rats. Basal concentrations of serum corticosterone did not differ between the two rat lines. Following stress, however, HAN rats showed slightly higher corticosterone secretion than SSN rats. Our results show that two sublines of the LEW inbred strain of rats show profound behavioural differences which are only marginally paralleled by differences at the level of the HPA system.     

Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in proximal rat trachea

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM) and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.     

Indicators and standards proposal for the evaluation of the quality of hospital care: the case for bronchial asthma

The objectives of this article are to propose indicators for evaluation of the quality of hospital management of bronchial asthma patients, based on explicit criteria from literature reviews. The central problem identified in the literature review is the erroneous evaluation of severity of asthma crises, either by patients and their relatives, or by health professionals at all levels of care, causing serious consequences not only for the patient, but for society as a whole. Mortality figures indicate that from 1980 to 1990, an average of 2000 deaths per year from asthma occurred in Brazil, of which 70% occurred in hospital. Asthma was the fourth cause of hospitalization (hospital admissions), in the state of Rio de Janeiro in 1993. Only 12% of the admissions that resulted in death made use of the ICU. The above information highlights the need for a thorough evaluation of hospital care of bronchial asthma in Brazil, including a review of all admissions resulting in death and reviews of a sample of all bronchial asthma admissions. Proposed criteria are for this evaluation include: severity of the crise, treatment prescribed, information given to the patient and their relatives, and follow-up appointments made after discharge from hospital.