Influence of normal mammary epithelium on breast cancer progression: the protective role of early pregnancy

AIMS AND BACKGROUND: The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue. METHODS: In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry. RESULTS: Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway. CONCLUSIONS: These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice

Techniques of intestinal transplantation in rat

Two surgical models of intestinal transplantation in the rat are described. One is the implantation of fetal and newborn intestine as free grafts into the omentum of adult recipients, the other the adult intestine transplantation as an accessory graft using vascular anastomoses. A hundred and sixteen small-bowel transplantations were done; 36 of which were fetal intestine (group I), 40 of newborn intestine (group II), and 40 of adult intestine (group III). In the fetal and newborn intestinal transplantation, we emphasize the practices that allowed us to avoid ischemic and traumatic injury to the graft. In the adult intestine transplantation with vascular anastomoses, we heighten the modifications in the surgical technique that made the operation easier and the strategies used to prevent hypothermia and hypovolemic shock. Once experienced with the two chosen surgical techniques, transplantation using an avascular segment became much easier and quicker than transplantation with vascular anastomose

Long COVID Symptoms in Non-Hospitalised Patients: A Retrospective Study

Introduction: The COVID-19 pandemic has presented numerous challenges to healthcare systems. As the number of affected individuals continues to rise, it is crucial to find preventive, diagnostic, and therapeutic approaches. This study aims to describe different COVID-19 sequelae within a Primary Health Care population.Methods: A retrospective cohort study was conducted in adults diagnosed with COVID-19 from March 2020 to April 2022, excluding pregnant women, minors, nursing home residents, hospitalizations, and deaths. Data was gathered from surveillance records on the Trace COVID-19 (R) platform, a pre-set original questionnaire (which included the Portuguese version of the World Health Organization's Quality of Life Assessment Instrument), and, if needed, patient electronic health records. Information on sociodemographic and clinical characteristics of acute COVID-19 was collected along with long COVID symptoms.Results: This study included 284 patients, aged 19 to 99 years old. The five most prevalent acute COVID-19 symptoms were fever (50.0%), tiredness (48.2%), myalgias (44.7%), dry cough (37.7%) and odynophagia (36.3%). Symptoms related to the neurological system (23.2%) and tiredness (22.9%) were the most prevalent in long COVID symptoms. Acute tiredness and arthralgia were associated with all long COVID outcomes. The associations between acute COVID-19 symptoms with long COVID outcomes were stronger for anosmia [OR = 5.07, 95% confidence interval (CI) 2.49 -10.36, p < 0.001] on a neurological chapter, acute tiredness for long lasting tiredness (OR = 4.07, 95% CI 2.07 -8.02, p = 0.041), fatigue for muscles and/or bones chapter (OR = 7.55, 95% CI 3.06 -18.66, p < 0.001), tiredness on an endocrine/hormonal chapter (OR = 6.54, 95% CI 2.37 -18.04, p < 0.001), dyspnea for respiratory symptoms (OR = 5.67, 95% CI 1.92 -16.74, p = 0.002) and fever for stomach or intestine symptoms (OR = 8.06, 95% CI 2.55 -25.47, p < 0.001). Almost all quality of life dimensions were negatively associated with the number of long COVID symptoms.Conclusion: A higher number of acute symptoms, as well as the presence of specific COVID-19 symptoms were associated with reported symptoms = 12 weeks after infection. In the studied population, an increased number of symptoms in both acute and long COVID had a significant negative impact on the perception of overall quality of life. The identification of these relationships could provide a new perspective for post-COVID care

Inhibition of ovine in vitro fertilization by anti-Prt antibody: hypothetical model for Prt/ZP interaction

BACKGROUND: The impact of prion proteins in the rules that dictate biological reproduction is still poorly understood. Likewise, the role of prnt gene, encoding the prion-like protein testis specific (Prt), in ram reproductive physiology remains largely unknown. In this study, we assessed the effect of Prt in ovine fertilization by using an anti-Prt antibody (APPA) in fertilization medium incubated with spermatozoa and oocytes. Moreover, a computational model was constructed to infer how the results obtained could be related to a hypothetical role for Prt in sperm-zona pellucida (ZP) binding. METHODS: Mature ovine oocytes were transferred to fertilization medium alone (control) or supplemented with APPA, or pre-immune serum (CSerum). Oocytes were inseminated with ovine spermatozoa and after 18 h, presumptive zygotes (n = 142) were fixed to evaluate fertilization rates or transferred (n = 374) for embryo culture until D6-7. Predicted ovine Prt tertiary structure was compared with data obtained by circular dichroism spectroscopy (CD) and a protein-protein computational docking model was estimated for a hypothetical Prt/ZP interaction. RESULTS: The fertilizing rate was lower (P = 0.006) in APPA group (46.0+/−6.79%) when compared to control (78.5+/−7.47%) and CSerum (64.5+/−6.65%) groups. In addition, the cleavage rate was higher (P < 0.0001) in control (44.1+/−4.15%) than in APPA group (19.7+/−4.22%). Prt CD spectroscopy showed a 22% alpha-helical structure in 30% (m/v) aqueous trifluoroethanol (TFE) and 17% alpha in 0.6% (m/v) TFE. The predominant alpha-helical secondary structure detected correlates with the predicted three dimensional structure for ovine Prt, which was subsequently used to test Prt/ZP docking. Computational analyses predicted a favorable Prt-binding activity towards ZP domains. CONCLUSIONS: Our data indicates that the presence of APPA reduces the number of fertilized oocytes and of cleaved embryos. Moreover, the CD analysis data reinforces the predicted ovine Prt trend towards an alpha-helical structure. Predicted protein-protein docking suggests a possible interaction between Prt and ZP, thus supporting an important role for Prt in ovine fertilization

Phenolic and furanic compounds of Portuguese chestnut and French, American and Portuguese oak wood chips

Botanical species used on aging process must be wisely and judiciously chosen, and for this selection, a basic knowledge of the chemical composition of woods is warranted. Aiming to contribute to extend the knowledge of the chemical composition of several wood species useful for enological purposes, we have focused our studies on Portuguese chestnut and French, American and Portuguese oak chips. The profile of low molecular weight phenolic composition of these chips was achieved, using an optimized extraction method based on pressurized liquid extraction, followed by the quantification of phenolic acids, phenolic aldehydes and furanic derivatives by high-performance liquid chromatography (HPLC-DAD). The identification of those compounds was also confirmed by LC-DAD/ESI-MS. This study allowed the determination of the low molecular phenolic composition of Portuguese chestnut and French, American and Portuguese oak wood. According to our results, the influence of the botanical species seems to be more relevant than the geographic origin of the wood species

Etiology of Diarrhea in Older Children, Adolescents and Adults: A Systematic Review

Diarrhea is an important cause of illness and death around the world and among people of all ages, but unfortunately we often do not know what specific bacterium or virus causes the illness. We conducted a review of the scientific literature with the goal of finding published studies that identified bacteria and viruses among patients with diarrhea in the community and in hospital settings. We initially found nearly 26,000 papers on this topic but narrowed the list to 22 studies that met all of our specific criteria for inclusion in our review. Among patients hospitalized for diarrhea, E coli and Vibrio cholerae were found in more than 49% of people living in middle income and poor countries. Among patients who sought care from their doctor on an outpatient basis, Salmonella spp., Shigella spp., and E. histolytica were most often found. In our review we focused on the differences in the distribution of pathogens between patients in inpatient vs. outpatient settings because these estimates may best approximate what we would expect to see if the distribution were applied to global estimates of diarrhea deaths vs. uncomplicated illnesses

Impact of volatile phenols and their precursors on wine quality and control measures of Brettanomyces/Dekkera yeasts

Volatile phenols are aromatic compounds and one of the key molecules responsible for olfactory defects in wine. The yeast genus Brettanomyces is the only major microorganism that has the ability to covert hydroxycinnamic acids into important levels of these compounds, especially 4-ethylphenol and 4-ethylguaiacol, in red wine. When 4-ethylphenols reach concentrations greater than the sensory threshold, all wine’s organoleptic characteristics might be influenced or damaged. The aim of this literature review is to provide a better understanding of the physicochemical, biochemical, and metabolic factors that are related to the levels of p-coumaric acid and volatile phenols in wine. Then, this work summarizes the different methods used for controlling the presence of Brettanomyces in wine and the production of ethylphenols

Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care

Search for continuous gravitational wave emission from the Milky Way center in O3 LIGO--Virgo data

We present a directed search for continuous gravitational wave (CW) signals emitted by spinning neutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presence of a numerous population of neutron stars has been reported in the literature, turning this region into a very interesting place to look for CWs. In this search, data from the full O3 LIGO--Virgo run in the detector frequency band $[10,2000]\rm~Hz$ have been used. No significant detection was found and 95$\%$ confidence level upper limits on the signal strain amplitude were computed, over the full search band, with the deepest limit of about $7.6\times 10^{-26}$ at $\simeq 142\rm~Hz$. These results are significantly more constraining than those reported in previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity and r-mode amplitude. These limits can be also translated into constraints in the black hole mass -- boson mass plane for a hypothetical population of boson clouds around spinning black holes located in the GC.Comment: 25 pages, 5 figure