Environmental pollutants are involved in the development and progression of numerous cancers, including cervical cancer (CC). One possible explanation for this is the ability of several pollutants to ...mimic natural hormones. This study aimed to evaluate the urinary concentrations of monoesters of phthalates and bisphenol A (BPA) in women with CC. A total of 45 women were included: 15 in the control group, 12 with CC diagnosis classified in early stages IA-IIB, and 18 in late stages III-IV. Urine samples were analyzed for BPA, mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono 2-ethylhexyl phthalate (MEHP) using high-performance liquid chromatography coupled to a tandem mass detector. The detection rate of environmental pollutants was 100%, with a median concentration in the control group and early-, and late-stage groups of 10.4, 9.2, 4.3, 38.4, and 12.9 µg L
−1
; 3.1, 3.1, 151.1, 54.5, and 30.4 µg L
−1
and 1.9, 92.8, 3.6, 31.0, and 9.3 µg L
−1
for BPA, MEHP, MBzP, MBP, and MiBP, respectively This study reveals high levels of phthalates, particularly MEHP, in urine samples of women with CC associated with human papillomavirus (HPV) infection. Further studies are needed to evaluate the possible role of phthalates in synergy with HPV in progression to CC.
Mortality following surgery for lung cancer increases at 90 days. The objective of this study was to determine the rate, factors, time to death, hospital stay until discharge, time to death after ...discharge and causes of mortality at 90 days following surgery for lung cancer.
A prospective follow-up study was performed in a cohort of 378 patients who underwent surgery for lung cancer between January 2012 and December 2016. Data on preoperative status, postoperative complications, and mortality were collected.
Rates of mortality were 1.6% vs. 3.2% at 30 and 90 days, respectively. Half of deaths occurred between 31 and 90 postoperative days following discharge.
The variables found to be related to mortality at 90 days were a Charlson Index >3 (p < 0.001), a history of stroke (p = 0.036), postoperative pneumonia (p = 0.001), postoperative pulmonary or lobar collapse (p = 0.001), reintubation (p < 0.001) and postoperative arrhythmia (p = 0.0029). The risk of mortality was also observed to be associated with the type of surgical technique –being higher for thoracotomy as compared to video-assisted thoracoscopy (VATS) (p = 0.011) –, and hospital readmission after discharge (p < 0.001). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Multivariate analysis revealed that a Charlson Index >3 (p = 0.001) OR 2.0 (1.55,2.78), a history of stroke (p = 0.018) OR 5.1 (1.81, 32.96) and postoperative pulmonary or lobar collapse (p = 0.001) OR 8.5 (2.41,30.22) were independent prognostic factors of mortality.
The most common causes of death were related to respiratory (58.3%) and cardiovascular (33.2%) complications.
Mortality at 90 days following surgery for lung cancer doubles 30-day mortality, which is a relevant finding of which both, patients and healthcare should be aware.
Half the deaths within 90 days after surgery for lung cancer occur after discharge.
Specific outpatient follow-up programs should be designed for patients at a higher risk of 90-day mortality.
ObjectiveTo describe mortality of in-hospital patients with COVID-19 and compare risk factors between survivors and non-survivors.DesignProspective cohort of adult inpatients.SettingTertiary ...healthcare teaching hospital in Guadalajara, Mexico.ParticipantsAll patients with confirmed COVID-19 hospitalised from 25 March to 7 September 2020 were included. End of study: 7 November 2020.Primary outcome measuresPatient survival analysed by the Kaplan-Meier method and comparison of factors by the log-rank test. Mortality risk factors analysed by multivariate Cox’s proportional-hazard model.ResultsOne thousand ten patients included: 386 (38%) died, 618 (61%) alive at discharge and six (0.6%) remained hospitalised. There was predominance of men (63%) and high frequency of overweight–obesity (71%); hypertension (54%); diabetes (40%); and lung (9%), cardiovascular (8%) and kidney diseases (11%); all of them significantly more frequent in non-survivors. Overweight–obesity was not different between groups, but severity of disease (Manchester Triage System and quick Sequential Organ Failure Assessment) was significantly worse in non-survivors, who were also significantly older (65 vs 45 years, respectively) and had haematological, biochemical, coagulation and inflammatory biomarkers more altered than survivors. Mortality predictors were invasive mechanical ventilation (IMV; OR 3.31, p<0.0001), admission to intensive care unit (ICU; OR 2.18, p<0.0001), age (OR 1.02, p<0.0001), Manchester Triage System (urgent OR 1.44, p=0.02; immediate/very urgent OR 2.02, p=0.004), baseline C reactive protein (CRP; OR 1.002, p=0.009) and antecedent of kidney disease (OR 1.58, p=0.04)ConclusionsMortality in hospitalised patients with COVID-19 in this emerging country centre seemed to be higher than in developed countries. Patients displayed a high frequency of risk factors for poor outcome, but the need for IMV, ICU admission, older age, more severe disease at admission, antecedent of kidney disease and higher CRP levels significantly predicted mortality.
Salmonella typhimurium invades the spleen, liver, and peripheral lymph nodes and has recently been detected in the bone marrow and thymus, resulting in a reduced thymic size and a decline in the ...total number of thymic cells. A specific deletion of the double‐positive cell subset has been characterized, yet the export of mature T cells to the periphery remains normal. We analyzed Salmonella pathogenesis regarding thymic structure and the T‐cell maturation process. We demonstrate that, despite alterations in the thymic structure, T‐cell development is maintained during Salmonella infection, allowing the selection of single‐positive T‐cell clones expressing particular T‐cell receptor beta chains (TCR‐Vβ). Moreover, the treatment of infected mice with an antibiotic restored the normal thymic architecture and thymocyte subset distribution. Additionally, the frequency of TCR‐Vβ usage after treatment was comparable to that in non‐infected mice. However, bacteria were still recovered from the thymus after 1 month of treatment. Our data reveal that a skewed T‐cell developmental process is present in the Salmonella‐infected thymus that alters the TCR‐Vβ usage frequency. Likewise, the post‐treatment persistence of Salmonella reveals a novel function of the thymus as a potential reservoir for this infectious agent.
Thymocytes subpopulations are modified during Salmonella infection. T‐cell repertoire is skewed by Salmonella infection. Antibiotics reverse Salmonella effects on thymus though bacteria persists in organ.
The objective of our study is to determine the thickness of the pubovisceral fasciculus of the levator ani muscle and the area of the genital hiatus by means of three-dimensional perineal ultrasound, ...in pregnant women in the 2nd trimester, and to analyze the related maternal, perinatal and postpartum clinical variables. Furthermore, to compare the results of our study with two similar series previously published. An observational, prospective study of pelvic floor ultrasound was carried out, performed at week 20, whose delivery was attended in the obstetrics service of the Hospital General Universitario Gregorio Marañón de Madrid (HGUGM), during the period of August from 2021 to June 2022. Maternal, ultrasound, perinatal and postpartum clinical variables were collected from each participant. During the study period, a total of 54 patients were included in it. The mean gestational age at which the ultrasound was performed was 19.81 ± 0.91 weeks. In relation to the ultrasound variables, the mean thickness of the pubovisceral muscle was 0.87 ± 0.13 cm (95% CI, 0.64-1.38 cm), while, in the plane of minimum dimension of the genital hiatus, the hiatal area at rest was 13.41 ± 3.22 (95% CI, 4.60-18.78) cm
. There is a significant correlation between the age of pregnant women (over 35 years of age) and the increase in the area of the genital hiatus (r = 0.295,
= 0.031). 3D ultrasound of the pelvic floor performed at week 20 of gestation can to be an effective, non-invasive, reproducible and cheap tool in the prognosis of the development of labor and of possible subsequent perineal dysfunctions.
Spinocerebellar ataxias (SCAs) are a group of hereditary and progressive neurological disorders characterized by a loss of balance and motor coordination typically associated with cerebellar atrophy. ...The most prevalent SCA types are all polyQ disorders like Huntington's disease, sharing the most relevant events in pathogenesis with this basal ganglia disorder, but with most of the damage concentrated in cerebellar neurons, and in their afferent and efferent connections (e.g., brainstem nuclei). SCAs have no cure and effective symptom-alleviating and disease-modifying therapies are not currently available. However, based on results obtained in studies conducted in murine models and information derived from analyses in
tissue samples from patients, which show notably higher levels of CB
receptors found in different cerebellar neuronal subpopulations, the blockade of these receptors has been proposed for acutely modulating motor incoordination in cerebellar ataxias, whereas their chronic activation has been proposed for preserving specific neuronal losses. Additional studies in
tissues from SCA patients have also demonstrated elevated levels of CB
receptors in Purkinje neurons as well as in glial elements in the granular layer and in the cerebellar white matter, with a similar profile found for endocannabinoid hydrolyzing enzymes, then suggesting that activating CB
receptors and/or inhibiting these enzymes may also serve to develop cannabinoid-based neuroprotective therapies. The present review will address both aspects. On one hand, the endocannabinoid system becomes dysregulated in the cerebellum and also in other CNS structures (e.g., brainstem, basal ganglia) in SCAs, which may contribute to the progression of pathogenic events in these diseases. On the other hand, these endocannabinoid alterations may be pharmacologically corrected or enhanced, and this may have therapeutic consequences, either alleviating specific symptoms or eliciting neuroprotective effects, an objective presently under investigation.
Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the ...high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA.
This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1.
Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level.
Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.
Highlights • The pathological phenotype in SCA-3 transgenic mice was associated with dysregulation of the endocannabinoid signaling. • Such endocannabinoid dysregulation was different depending on ...the specific CNS areas investigated. • Opposite changes in CB1 receptor signaling were seen in the Purkinje cell layer compared to the cerebellar dentate nucleus. • An elevated FAAH-mediated degradation of endocannabinoids was seen in the brainstem.
Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 ...patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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