Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine ...whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients.
Observational and prospective study.
Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain).
COVID-19 patients admitted in ICU and healthy subjects.
Determination of HLA genetic polymorphisms.
Mortality at 30 days.
A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p=0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p=0.02) and HLA-C*16 (p=0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR=7.693; 95% CI=1.063-55.650; p=0.04) or APACHE-II (OR=11.858; 95% CI=1.524-92.273; p=0.02), the allele HLA-C*01 after controlling for SOFA (OR=11.182; 95% CI=1.053-118.700; p=0.04) or APACHE-II (OR=17.604; 95% CI=1.629-190.211; p=0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR=9.963; 95% CI=1.235-80.358; p=0.03).
The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.
Psychological impact of quarantine on healthcare workers Gómez-Durán, Esperanza L; Martin-Fumadó, Carles; Forero, Carlos G
Occupational and environmental medicine (London, England),
10/2020, Letnik:
77, Številka:
10
Journal Article
Recenzirano
ObjectivesExposure to infection is an inherent occupational risk for healthcare workers and may lead them to undergo quarantine during disease outbreaks. Both front-line battle and quarantine are ...stressful experiences that may make psychological support for healthcare workers necessary. Psychological support measures based on the best available evidence should be included in emergency plans worldwide. We summarise the research evidence on the psychological impact of quarantine on healthcare workers.MethodsWe retrieved 470 articles on the psychological impact of quarantine on healthcare workers from the Web of Science and included in this review all 12 articles that met our inclusion criteria.ResultsThe reviewed studies reported acute stress during quarantine and long-lasting depressive, post-traumatic stress and alcohol dependency and abuse symptoms. Healthcare workers fear infection for themselves, but more so for their loved ones, and are also concerned about the stigma that may affect their families, most especially their children.ConclusionsThe safety of healthcare workers and their families during disease outbreaks needs to be ensured. Suitable alternative accommodation and personalised monitoring during quarantine are useful intervention measures to prevent adverse effects in healthcare workers. Clear public health communication will help reduce uncertainty, guilt and stigma. Financial aid should be considered for the more severely affected workers. Finally, mental healthcare for healthcare workers should be a priority, as quarantines can be a mental distress trigger. The development of efficient referral paths and the provision of counselling or psychotherapy during the confinement period are an opportunity for early mental health interventions.
Phytophthora cinnamomi
is an important plant pathogen responsible for dieback diseases in plant genera including
Quercus
,
Fagus
,
Castanea
,
Eucalyptus
, and
Pinus
, among others, all over the world
.... P. cinnamomi
infection exerts tremendous ecological and economic losses. Several strategies have been developed to combat this pathogenic oomycete, including the search for novel anti-oomycete compounds. In this work, a Mediterranean vascular plant,
Phlomis purpurea
, has been screened for secondary bioactivity against this pathogen. The genus
Phlomis
includes a group of herbaceous plants and shrubs described as producers of many different bioactive compounds, including several triterpenoids. Triterpenoids are well-known molecules synthesized by plants and microorganisms with potent antioxidant, antitumoral, and antimicrobial activities. We have isolated by HPLC-DAD and characterized by HPLC-MS and NMR two nortriterpenoid compounds (phlomispentaol A and phlomispurtetraolone) from the root extracts of
P. purpurea.
One of them (phlomispentaol A) is active against the plant pathogenic oomycete
P. cinnamomi
(based on
in vitro
inhibition bioassays). Based on their chemical structure and their relationship to other plant triterpenoids, oleanolic acid is proposed to be the common precursor for these molecules. The anti-oomycete activity shown by phlomispentaol A represents a promising alternative to counteract the worldwide-scale damage caused to forest ecosystems by this pathogen.
Novel strategies based on spray-pyrolysis deposition are proposed to increase the triple-phase boundary (TPB) of La0.8Sr0.2MnO3−δ (LSM) cathodes in contact with yttria-stabilized zirconia (YSZ) ...electrolyte: (i) nanocrystalline LSM films deposited on as-prepared YSZ surface; (ii) the addition of poly(methyl methacrylate) microspheres as pore formers to further increase the porosity of the film cathodes; and (iii) the deposition of LSM by spray pyrolysis on backbones of Zr0.84Y0.16O1.92 (YSZ), Ce0.9Gd0.1O1.95 (CGO), and Bi1.5Y0.5O3−δ (BYO) previously fixed onto the YSZ. This last method is an alternative to the classical infiltration process with several advantages for large-scale manufacturing of planar solid oxide fuel cells (SOFCs), including easier industrial implementation, shorter preparation time, and low cost. The morphology and electrochemical performance of the electrodes are investigated by scanning electron microscopy and impedance spectroscopy. Very low values of area specific resistance are obtained, ranging from 1.4 Ω·cm2 for LSM films deposited on as-prepared YSZ surface to 0.06 Ω-cm2 for LSM deposited onto BYO backbone at a measured temperature of 650 °C. These electrodes exhibit high performance even after annealing at 950 °C, making them potentially suitable for applications in SOFCs at intermediate temperatures.
Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast ...cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.
One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m
) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method.
Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR HR = 0.30; 95% confidence interval (CI), 0.14-0.62;
= 0.0001. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63;
= 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.
Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.
Background
Vincristine is a commonly used chemotherapeutic agent. It is associated with undesirable digestive side effects. However, the impact of vincristine on gastrointestinal structure and ...motility or its long‐term effects have not been deeply studied in animal models. This could be useful in order to develop therapeutic or preventive strategies for cancer patients. The aim of this study was to analyze such effects.
Methods
Rats received saline or vincristine (0.1 mg kg−1, ip) daily for 10 days. Evaluations were performed during treatment and 2‐6 weeks after. Somatic mechano‐sensitivity was assessed using von Frey hairs. Gastrointestinal motor function was studied by means of radiographic still images and colonic propulsion of fecal pellets using fluoroscopy videos. Histological assessment of the gut morphology and immunohistochemistry for HuC/D and nNOS were performed in whole‐mount myenteric plexus preparations.
Key Results
Peripheral sensitivity was increased in animals treated with vincristine and did not subside 2 weeks after treatment finalization. Vincristine treatment inhibited gastrointestinal motility although this was recovered to normal values with time. Damage in the digestive wall after vincristine treatment was greater in the ileum than in the colon. Villi shortening (in ileum) and large inflammatory nodules still remained 2 weeks after treatment finalization. Finally, the proportion of nNOS‐immunoreactive neurons was increased with vincristine and continued to be increased 2 weeks after treatment finalization.
Conclusions and Inferences
Vincristine alters gastrointestinal motility, peripheral sensitivity and mucosal architecture. Vincristine‐induced neuropathy (somatic and enteric), intestinal mucosa damage and inflammatory infiltrations are relatively long‐lasting.
The effects produced by vincristine repeatedly administered in rats are described. Although reduction in general gastrointestinal motility and colonic propulsion of fecal pellets seem to recover after treatment, vincristine‐induced neuropathy (somatic and enteric), intestinal mucosa damage and inflammatory infiltrations are relatively long‐lasting. Sequelae of chemotherapy should be more closely monitored.
Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of ...topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.
The North American (NOAM) plate converges with the Caribbean (CARIB) plate at a rate of 20.0 ± 0.4 mm/yr. towards 254 ± 1°. Plate convergence is highly oblique (20–10°), resulting in a complex ...crustal boundary with along-strike segmentation, strain partitioning and microplate tectonics. We study the oblique convergence of the NOAM and CARIB plates between southeastern Cuba to northern Puerto Rico using new swath multibeam bathymetry data and 2D multi-channel seismic profiles. The combined interpretation of marine geophysical data with the seismicity and geodetic data from public databases allow us to perform a regional scale analysis of the shallower structure, the seismotectonics and the slab geometry along the plate boundary. Due to differential rollback between the NOAM oceanic crust north of Puerto Rico and the relative thicker Bahamas Carbonate Province crust north of Hispaniola a slab tear is created at 68.5°W. The northern margin of Puerto Rico records the oblique high-dip subduction and rollback of the NOAM plate below the island arc. Those processes have resulted in a forearc transpressive tectonics (without strain partitioning), controlled by the Septentrional-Oriente Fault Zone (SOFZ) and the Bunce Fault Zone (BFZ). Meanwhile, in the northern margin of Hispaniola, the collision of the Bahamas Carbonate Province results in high plate coupling with strain partitioning: SOFZ and Northern Hispaniola Deformed Belt (NHDB). In the northern Haitian margin, compression is still relevant since seismicity is mostly associated with the deformation front, whereas strike slip earthquakes are hardly anecdotal. Although in Hispaniola intermediate-depth seismicity should disappear, diffuse intermediate-depth hypocenter remains evidencing the presence of remnant NOAM subducted slab below central and western Hispaniola. Results of this study improve our understanding of the active tectonics in the NE Caribbean that it is the base for future assessment studies on seismic and tsunamigenic hazard.
•Along-strike variations of tectonic framework in northeastern Caribbean margin are studied.•Shallow plate boundary structure related to the slab geometry has been defined.•First-order fault systems and its associated features have been mapped along the margin.
Leaky urban drainage networks (UDNs) exfiltrating wastewater can contaminate aquifers. Detailed knowledge on spatiotemporal distributions of water-dissolved, sewer-borne contaminants in groundwater ...is essential to protect urban aquifers and to optimize monitoring systems. We evaluated the effect of UDN layouts on the spreading of sewer-borne contaminants in groundwater using a parsimonious approach. Due to the UDN’s long-term leakage behavior and the existence of non-degradable sewer-borne contaminants (equivalent to a conservative and constant contaminant source), we employed a concept of horizontal line sources to mimic the UDN layout. This does not require the consideration of bio-degradation processes or temporal delay and effectively bypasses the vadose zone, thus reducing computational requirements associated with a full simulation of leakages. We used a set of synthetic leakage scenarios which were generated using fractals and are based on a real-world UDN layout. We investigated the effects of typical leakage rates, varying groundwater flow directions, and UDN’s layouts on the shape of the contaminant plume, disregarding the resulted concentration. Leakage rates showed minimal effects on the total covered plume area, whereas 89% of the variance of the plume’s geometry is explained by both the UDN’s layout (e.g., length and level of complexity) and groundwater flow direction. We demonstrated the potential of applying this approach to identify possible locations of groundwater observation wells using a real UDN layout. This straightforward and parsimonious method can serve as an initial step to strategically identify optimal monitoring systems locations within urban aquifers, and to improve sewer asset management at city scale.
Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular ...diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of β-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.
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•Animal venom is an important source of numerous proteins that can be used as new therapeutic agents.•New therapeutic options are needed for treatment of diverse human pathologies.•Animal venom derived molecules have beneficial properties against several diseases, including chronic-degenerative illnesses.•Pre-clinical studies of animal venom derived molecules are key for the study and development of new therapeutic strategies.
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