G protein-coupled receptors (GPCRs) control crucial physiological processes and their dysfunction contributes to various human diseases, including cancer. The orphan GPCR GPR55 was identified and ...cloned more than a decade ago, but very little is known about its physio-pathological relevance. It has been recently shown that GPR55 controls the behavior of human cancer cell lines in culture and xenografts. However, the assessment of the actual role of this receptor in malignant transformation in vivo is hampered by the lack of studies on its functional impact in clinically-relevant models of cancer. Here we demonstrate that GPR55 drives mouse skin tumor development. Thus, GPR55-deficient mice were more resistant to DMBA/TPA-induced papilloma and carcinoma formation than their wild-type littermates. GPR55 exerted this pro-tumor effect primarily by conferring a proliferative advantage on cancer cells. In addition, GPR55 enhanced skin cancer cell anchorage-independent growth, invasiveness and tumorigenicity in vivo, suggesting that it promotes not only tumor development but also tumor aggressiveness. Finally, we observed that GPR55 is upregulated in human skin tumors and other human squamous cell carcinomas compared with the corresponding healthy tissues. Altogether, these findings reveal the pivotal importance of GPR55 in skin tumor development, and suggest that this receptor may be used as a new biomarker and therapeutic target in squamous cell carcinomas.
The measurement of trace element concentration in aerosols is of interest for environmental studies and for human health assessment. The temporal variability of total suspended particles (TSP) and ...its elemental composition in Seville, in SW Spain, is of particular complexity since Atlantic air masses and Saharan Dust Intrusions (SDI) overlap to local natural and anthropogenic sources. This paper is aimed to study the temporal evolution (in a monthly basis) of the concentrations of 25 trace elements, determined by ICP-MS, in high-volume air filter samples from Seville, covering a two-year period: 2001–2002. The mean TSP value for this period was 79.7μgm−3 and showed peak values in August 2001 and June 2002, likely related to SDI. Enrichment factors (EF) for Se, Sb and Zn and Pb were above 100, which revealed their anthropogenic sources. The comparison among EF from Seville and Huelva, a highly industrialized city nearby Seville, showed higher levels of anthropogenic elements there than in Seville. Simulations of the transport/dispersion of pollutants starting in Huelva confirm that air pollutants can reach Seville in the course of around 6hours although they do not contribute significantly to the levels found in this city. A significant temporal correlation was found between elements which have a common source, being crustal (Al, Ti, Be, Co, Cs, Fe, Cr, Mn, U, Sr and Th) or anthropogenic sources (Zn, Pb, Cd). The temporal variations of those crustal elements are similar and related with the TSP levels for both years, with the clearly visible peaks probably related with the Saharan dust intrusion.
•The mean TSP value for the period 2001–2002 in the air of Seville was (79.7±12.6) μg m−3.•The TSP values showed a peak value in August 2001, likely attributable to SDI events.•EF for Se, Sb, Zn and Pb was above 100, revealing their anthropogenic sources.•Crustal elements' temporal variations were related with TSP levels for both years.
Determination of antibodies against ToRCH antigens at the beginning of pregnancy allows assessment of both the maternal immune status and the risks to an adverse pregnancy outcome. Age-standardised ...seroprevalences were determined in sera from 1009 women of childbearing age residing in Mexico, Brazil, Germany, Poland, Turkey or China using a multiparametric immunoblot containing antigen substrates for antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex viruses (HSV-1, HSV-2), Bordetella pertussis, Chlamydia trachomatis, parvovirus B19, Treponema pallidum and varicella zoster virus (VZV). Seroprevalences for antibodies against HSV-1 were >90% in samples from Brazil and Turkey, whereas the other four countries showed lower mean age-adjusted seroprevalences (range: 62.5–87.9%). Samples from Brazilian women showed elevated seroprevalences of antibodies against HSV-2 (40.1%), C. trachomatis (46.8%) and B. pertussis (56.6%) compared to the other five countries. Seroprevalences of anti-T. gondii antibodies (0.5%) and anti-parvovirus B19 antibodies (7.5%) were low in samples from Chinese women, compared to the other five countries. Samples from German women revealed a low age-standardised seroprevalence of anti-CMV antibodies (28.8%) compared to the other five countries. These global differences in immune status of women in childbearing age advocate country-specific prophylaxis strategies to avoid infection with ToRCH pathogens.
Abstract
Background
Nursing homes are highly vulnerable to the occurrence of COVID-19 outbreaks, which result in high lethality rates. Most of them are not prepared to severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) pandemic.
Method
A coordinated on-site medicalization program (MP) in response to a sizeable COVID-19 outbreak in 4 nursing homes was organized, with the objectives of improving survival, offering humanistic palliative care to residents in their natural environment, and reducing hospital referrals. Ten key processes and interventions were established (provision of informatics infrastructure, medical equipment, and human resources, universal testing, separation of “clean” and “contaminated” areas, epidemiological surveys, and unified protocols stratifying for active or palliative care approach, among others). Main outcomes were a composite endpoint of survival or optimal palliative care (SOPC), survival, and referral to hospital.
Results
Two hundred and seventy-two of 457 (59.5%) residents and 85 of 320 (26.5%) staff members were affected. The SOPC, survival, and referrals to hospital occurred in 77%, 72.5%, and 29% of patients diagnosed before the start of MP, with respect to 97%, 83.7%, and 17% of those diagnosed during the program, respectively. The SOPC was independently associated to MP (OR = 15 3–81); and survival in patients stratified to active approach, to the use of any antiviral treatment (OR = 28 5–160). All outbreaks were controlled in 39 37–42 days.
Conclusions
A coordinated on-site MP of nursing homes with COVID-19 outbreaks achieved a higher SOPC rate, and a reduction in referrals to hospital, thus ensuring rigorous but also humanistic and gentle care to residents.
Bioactive peptides derived from diverse food proteins have been part of diverse investigations. Whey is a rich source of proteins and components related to biological activity. It is known that ...proteins have effects that promote health benefits. Peptides derived from whey proteins are currently widely studied. These bioactive peptides are amino acid sequences that are encrypted within the first structure of proteins, which required hydrolysis for their release. The hydrolysis could be through in vitro or in vivo enzymatic digestion and using microorganisms in fermented systems. The biological activities associated with bio-peptides include immunomodulatory properties, antibacterial, antihypertensive, antioxidant and opioid, etc. These functions are related to general conditions of health or reduced risk of certain chronic illnesses. To determine the suitability of these peptides/ingredients for applications in food technology, clinical studies are required to evaluate their bioavailability, health claims, and safety of them. This review aimed to describe the biological importance of whey proteins according to the incidence in human health, their role as bioactive peptides source, describing methods, and obtaining technics. In addition, the paper exposes biochemical mechanisms during the activity exerted by biopeptides of whey, and their application trends.
INTRODUCTIONThe global pandemic of COVID-19 has led to rapid implementation of telemedicine, but there is little information on patient satisfaction of this system as an alternative to face-to-face ...care. OBJECTIVETo evaluate urological patient satisfaction with teleconsultation during the COVID-19 pandemic. MATERIAL AND METHODSObservational, prospective, cross-sectional, non-interventional study carried out by telephone survey during the period considered as the peak of the pandemic (March-April 2020). A quality survey composed of 11 questions on urological care provided by physicians during the COVID-19 pandemic was conducted, selecting a representative sample of patients attended by teleconsultation. RESULTSTwo hundred patients were contacted by telephone to answer a survey on the quality of teleconsultation. The distribution of patients surveyed among the specialized consultations was homogeneous with the number of consultations cited in the period; 18% of them required assistance from family members. Sixty percent of patients avoided going to a medical center during the pandemic. Of the surveyed patients, 42% had cancelled diagnostic tests, 59% had cancelled medical consultations, 3.5% had cancelled treatments and 1% had cancelled interventions. Ten percent reported a worsening of urological symptoms during confinement. According to physicians, consultations were effectively delivered in 72% of cases, with teleconsultation being carried out by their usual urologist in 81%. Teleconsultation overall satisfaction level was 9 (IQI8-10), and 61.5% of respondents consider teleconsultation as a «health care option» after the healthcare crisis. CONCLUSIONTeleconsultation has been evaluated with a high level of satisfaction during the COVID-19 pandemic, offering continuous care to urological patients during the healthcare crisis. The perceived quality offers a field of optional telematic assistance in selected patients, which should be re-evaluated in a period without confinement measures.
Background and Purpose
PPARβ enhances insulin sensitivity in adipocytes and skeletal muscle cells, but its effects on insulin signalling in endothelial cells are not known. We analysed the effects of ...the PPARβ/δ (PPARβ) agonists, GW0742 and L165041, on impaired insulin signalling induced by high glucose in HUVECs and aortic and mesenteric arteries from diabetic rats.
Experimental Approach
Insulin‐stimulated NO production, Akt‐Ser473 and eNOS‐Ser1177 phosphorylation, and reactive oxygen species (ROS) production were studied in HUVECs incubated in low‐ or high‐glucose medium. Insulin‐stimulated relaxations and protein phosphorylation in vessels from streptozotocin (STZ)‐induced diabetic rats were also analysed.
Key Results
HUVECs incubated in high‐glucose medium showed a significant reduction in insulin‐stimulated production of NO. High glucose also reduced insulin‐induced Akt‐Ser473 and eNOS‐Ser1177 phosphorylation, increased IRS‐1‐Ser636 and ERK1/2‐Thr183‐Tyr185 phosphorylation and increased ROS production. The co‐incubation with the PPARβ agonists GW0742 or L165041 prevented all these effects induced by high glucose. In turn, the effects induced by the agonists were suppressed when HUVEC were also incubated with the PPARβ antagonist GSK0660, the pyruvate dehydrogenase kinase (PDK)4 inhibitor dichloroacetate or after knockdown of both PPARβ and PDK4 with siRNA. The ERK1/2 inhibitor PD98059, ROS scavenger catalase, inhibitor of complex II thenoyltrifluoroacetone or uncoupler of oxidative phosphorylation, carbonyl cyanide m‐chlorophenylhydrazone, also prevented glucose‐induced insulin resistance. In STZ diabetic rats, oral GW0742 also improved insulin signalling and the impaired NO‐mediated vascular relaxation.
Conclusion and Implications
PPARβ activation in vitro and in vivo restores the endothelial function, preserving the insulin‐Akt‐eNOS pathway impaired by high glucose, at least in part, through PDK4 activation.
Whether cirrhotic patients with
Streptococcus bovis
bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating ...associations between
S. bovis
biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with
S. bovis
bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in
S. bovis
biotype I (
S. gallolyticus
) bacteremia (80%) than in
S. bovis
biotype II (33.3%;
p
< 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with
S. gallolyticus
bacteremia.
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