The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos, which is inconsistent with the expectation from atmospheric backgrounds at a ...significance greater than 5σ. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from 2010 May to 2012 May. We show that compared to the classic approach using tracks, this statistically independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations $\lesssim$−30°.
Bovine colostrum contains compounds, which provide passive immune protection from mother to newborn calves. Little is known about cytokine levels and their role in bovine colostrum. Moreover, the ...capacity of bovine colostrum cells to mount specific immune responses after natural exposure to bovine tuberculosis (bTB) antigens in dairy herds has not been studied, thus far. The purpose of this study was to identify biomarkers for bTB infection measurable in bovine colostrum. The present study reveals that isolated-immune colostrum cells can mount a specific immune response against bTB antigens, by measuring the novo IFN-γ release in cell culture. We found that IFN-γ levels in the responders (Bov+) to bTB antigen were higher than in non-responders (Bov−). On the other hand, proinflammatory cytokines contained in colostrum's whey were tested in Tuberculin Skin Test (TST) reactor (TST+) and non-reactor (TST−) animals to assess their potential role as biomarker. We observed that IFN-γ levels were lower or undetectable, as opposed to IL4 levels were measurable, the TNF-α level was higher in TST− than TST+, while IL-6 levels showed the opposite reaction and with no statistical significance. Moreover, IL-1α mRNA expression levels were higher in colostrum mononuclear cells (CMC) in Bov+ cattle. Collectively, these data suggest that the differential expression of pro and anti-inflammatory cytokines could have relevant value to diagnose bTB in cattle.
•Cytokines presented in this work, have the potential to be used as diagnosis of bTB in bovine colostrum.•IL-1-α and TNF-α in colostrum have a suitable mean to identify reactors and non-reactor cattle to bTB.•Current diagnostic screening can be improve by IL-1-α and TNF-α, and can be implemented in dairy herds.
Inside Cover: In article number 2200262, Carlos Guerrero‐Sánchez and co‐workers present on the cover image the solution complexity of all‐aqueous, surfactant‐free and pH‐driven formation of ...dual‐responsive polymeric nanoparticles. Moreover, it indicates the potential use of those as nanocarriers by exploring the encapsulation and release of drugs with a pH‐dependent solubility.
Abstract Introduction Protein phosphorylation plays an important role in the modulation of steroidogenesis and it depends on the activation of different signaling cascades. Previous data showed that ...PKA activity is related to steroidogenesis in mitochondria from syncytiotrophoblast of human placenta (HPM). PKA localization and contribution in progesterone synthesis and protein phosphorylation of HPM was assessed in this work. Methods Placental mitochondria and submitochondrial fractions were used. Catalytic and regulatory PKA subunits were identified by Western blot. PKA activity was determined by the incorporation of32 P into proteins in the presence or absence of specific inhibitors. The effect of PKA activators and inhibitors on steroidogenesis and protein phosphorylation in HPM was tested by radioimmunoassay and autoradiography. Results The PKAα catalytic subunit was distributed in all the submitochondrial fractions whereas βII regulatory subunit was the main isoform observed in both the outer and inner membranes of HPM. PKA located in the inner membrane showed the highest activity. Progesterone synthesis and mitochondrial protein phosphorylation are modified by inhibitors of PKA catalytic subunit but are neither sensitive to inhibitors of the regulatory subunit nor to activators of the holoenzyme. Discussion The lack of response in the presence of PKA activators and inhibitors of the regulatory subunit suggests that the activation of intramitochondrial PKA cannot be prevented or further activated. Conclusions The phosphorylating activity of PKA inside HPM could be an important component of the steroidogenesis transduction cascade, probably exerting its effects by direct phosphorylation of its substrates or by modulating other kinases and phosphatases.
Pre-diabetes in young people is frequently unrecognized or not treated on time, with the consequent loss of opportunity for diabetes prevention. In Mexico, there is scarce information about the ...prevalence of pre-diabetes in young adults.
To determine the prevalence and risk factors for pre-diabetes in young Mexican adults in primary health care.
In a cross-sectional study, 288 subjects, aged 18-30 years, from a primary care unit were included. Pre-diabetes was diagnosed (according to the criteria of the American Diabetes Association) as impaired fasting glucose (8-12 hours fasting plasma glucose level: 100-125 mg/dl) or impaired glucose tolerance (140-199 mg/dl after a 2-hour oral glucose tolerance test).
Prevalence of pre-diabetes was 14.6% 95% confidence interval (CI): 10.7-19.2, whereas that of diabetes was 2.4% (95% CI: 1.0-4.9). A high proportion of patients had history of obesity, diabetes, hypertension and consumption of tobacco and alcohol. Pre-diabetic patients were older than normoglycaemics (pre-diabetic patients: 26±4 years versus normoglycaemic subjects: 24±3 years, P = 0.003) and had higher body mass index (BMI; pre-diabetic patients: 29.4±6.8 kg/m(2) versus normoglycaemic subjects: 26.8±5.8 kg/m(2); P = 0.009), particularly in the case of men (pre-diabetic men: 29.3±7.0 kg/m(2) versus normoglycaemic men: 26.4±5.1 kg/m(2); P = 0.03). Although waist circumference showed a trend to be higher among pre-diabetics, no significant differences were found according to gender (among males: pre-diabetics: 99.5±18.8 cm versus normoglycaemics: 93.3±14.4 cm, P = 0.09; among females: pre-diabetics: 91.5±13.8 cm versus normoglycaemics: 85.8±15.9 cm, P = 0.16). Only age and BMI were significantly associated with the presence of pre-diabetes.
Almost 15% of these young adults had pre-diabetes. Many modifiable and non-modifiable risk factors were present in these patients, but only age and a higher BMI were independent variables significantly associated with pre-diabetes. Timely interventions in primary health care are needed to prevent or delay the progression to diabetes.
Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (T(H)2), autoantibodies, and CD8+ T ...cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin Ig E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD.
We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored.
Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study.
With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD.
Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton ...Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes.
1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category.
The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m
, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight.
EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.
BACKGROUND AND OBJECTIVESIt is necessary to expand the knowledge in the use of apremilast in clinical practice. The APPRECIATE study (NCT02740218) aims to describe the characteristics of patients ...with psoriasis treated with apremilast, to evaluate their perspectives and those of dermatologists, as well as the outcomes obtained in clinical practice in Spain. METHODSObservational, retrospective, cross-sectional, multicenter study of patients with chronic plaque psoriasis who could be contacted 6 (±1) months after apremilast initiation. The data were obtained from medical records and questionnaires from patients and physicians. RESULTSA total of 80 patients were evaluated; at apremilast onset, they showed mean (standard deviation, SD) Psoriasis Area and Severity Index (PASI) = 8.3 (5.3), mean (SD) Dermatology Life Quality Index (DLQI) = 8.9 (6.6). At six months, 58.8% (n=47) of patients continued apremilast treatment (discontinuations due to lack of efficacy 16.3%, safety/tolerability 20.0%). In patients continuing treatment, PASI75 was achieved by 36.7% of patients; mean (95% CI) DLQI score was 2.2 (0.7-3.6) and mean (SD) Patient Benefit Index score was 2.8 (0.8). Compliance with physicians' expectations was correlated with benefits reported by patients (r=0.636). Adverse events were reported by 56.3% of patients (the most common were diarrhoea and nausea). CONCLUSIONSPatients receiving apremilast for 6 months in Spanish clinical practice, reported substantial improvements in their quality of life (mean DLQI reduced by more than 6 points) and disease severity (PASI75 achieved by over one-third of patients), despite less skin involvement than patients who enrolled in clinical trials.
The simultaneous measurement of transverse load and temperature using two long-period fiber gratings multiplexed in the wavelength domain is presented experimentally. For this, a mechanically induced ...long-period fiber grating (MI-LPFG) and a long-period fiber grating inscribed by a continuous-wave CO2 laser (CO2 LPFG) are connected in cascade. First, the transverse load and the temperature measurements were individually performed by the multiplexed long-period fiber gratings configuration. The MI-LPFG is subject to a transverse load variation from 0–2000 g with steps of 500 g, whereas the CO2 LPFG is unloaded and they are kept at room temperature. Similarly, the CO2 LPFG is subject to a temperature variation from 30 to 110 °C by increments of 20 °C, while the MI-LPFG with a constant transverse load of 2000 g is kept at room temperature. Subsequently, the simultaneous measurement of the transverse load and the temperature is performed by the multiplexed long-period fiber grating following the steps outlined above. According to the experimental results, the transverse load and temperature measurement present high repeatability for the individual and simultaneous process. Moreover, the multiplexed LPFGs exhibit low cladding-mode crosstalk of transverse load and temperature. The coarse wavelength-division multiplexing (CWDM) of long-period fiber gratings is an attractive alternative technique in optical fiber distributed sensing applications.
Current literature shows the association of post-intubation hypotension and increased odds of mortality in critically ill non-trauma and trauma populations. However, there is a lack of research on ...potential interventions that can prevent or ameliorate the consequences of endotracheal intubation and thus improve the prognosis of trauma patients with post-intubation hypotension. This review paper hypothesizes that the deployment of REBOA among trauma patients with PIH, by its physiologic effects, will reduce the odds of mortality in this population. The objective of this paper is to review the current literature on REBOA and post-intubation hypotension, and, furthermore, to provide a rational hypothesis on the potential role of REBOA in severely injured patients with post-intubation hypotension.
PDF
