The insertion of a nasogastric (NG) tube is often a difficult experience for both patients and caregivers. This often results in a high failure rate of NG insertion. This pilot study aimed to ...evaluate the effectiveness, tolerance, and acceptability of hypnoanalgesia to assist self-insertion of an NG tube. Patients undergoing high-dose chemotherapy for autologous or allogeneic hematopoietic stem cell transplantation (HSCT) or acute leukemia and with high risk of aplasia were included in the study. A total of 38 patients were included during 6 consecutive months. They all achieved successful NG tube self-insertion. The NG tube remained in place during hospitalization in 32 cases for an average duration of 15 days. Six patients rejected the NG tube during vomiting but they all voluntarily attempted it again later on and succeeded. The discomfort related to NG-tube insertion was mild. This pilot study suggests that NG tube self-insertion assisted by hypnoanalgesia may be effective, well-accepted, and well-tolerated in patients. These promising findings will need further confirmation.
The insertion of a nasogastric (NG) tube is often a difficult experience for both patients and caregivers. This often results in a high failure rate of NG insertion. This pilot study aimed to ...evaluate the effectiveness, tolerance, and acceptability of hypnoanalgesia to assist self-insertion of an NG tube. Patients undergoing high-dose chemotherapy for autologous or allogeneic hematopoietic stem cell transplantation (HSCT) or acute leukemia and with high risk of aplasia were included in the study. A total of 38 patients were included during 6 consecutive months. They all achieved successful NG tube self-insertion. The NG tube remained in place during hospitalization in 32 cases for an average duration of 15 days. Six patients rejected the NG tube during vomiting but they all voluntarily attempted it again later on and succeeded. The discomfort related to NG-tube insertion was mild. This pilot study suggests that NG tube self-insertion assisted by hypnoanalgesia may be effective, well-accepted, and well-tolerated in patients. These promising findings will need further confirmation.
Exposure to fine-particulate air pollution is a major global health concern because it is associated with reduced birth weight and an increased risk of cardiovascular disease. Here we have ...investigated the potential for exposure to diesel exhaust during pregnancy to influence mammary gland development and milk composition. Female rabbits were therefore exposed by nose-only inhalation to either diluted diesel exhaust fumes (1 mg/m3) or clean air for 2h/day, 5 days/week, from the 3rd to the 27th days of pregnancy. On Day 28 of pregnancy, mammary glands were collected from twelve females (six controls and six diesel-exposed) and assessed for morphological and functional alterations. Milk samples were collected from eighteen dams (nine controls and nine diesel-exposed) during early (days 2 to 4) and established (days 13 to 16) lactation to verify the composition of fatty acids and major proteins and leptin levels. The mammary alveolar lumina contained numerous fat globules, and stearoyl CoA reductase expression was higher in mammary epithelia from diesel exhaust-exposed rabbits, which together suggested increased mammary lipid biosynthesis. Gas chromatography analysis of the composition of milk fatty acids revealed a sharp rise in the total fatty acid content, mainly due to monounsaturated fatty acids. Liquid chromatography-mass spectrometry analysis of milk samples enabled identification and quantification of the main rabbit milk proteins and their main phosphorylated isoforms, and revealed important changes to individual casein and whey protein contents and to their most phosphorylated isoforms during early lactation. Taken together, these findings suggest that repeated daily exposure to diesel exhaust fumes during pregnancy at urban pollution levels can influence lipid metabolism in the mammary gland and the lipid and protein composition of milk. As milk may contribute to metabolic programming, such alterations affecting milk composition should be taken into account from a public health perspective.
Lactation is an essential process for mammals. In sheep, the R96C mutation in suppressor of cytokine signaling 2 (SOCS2) protein is associated with greater milk production and increased mastitis ...sensitivity. To shed light on the involvement of R96C mutation in mammary gland development and lactation, we developed a mouse model carrying this mutation (SOCS2KI/KI). Mammary glands from virgin adult SOCS2KI/KI mice presented a branching defect and less epithelial tissue, which were not compensated for in later stages of mammary development. Mammary epithelial cell (MEC) subpopulations were modified, with mutated mice having three times as many basal cells, accompanied by a decrease in luminal cells. The SOCS2KI/KI mammary gland remained functional; however, MECs contained more lipid droplets versus fat globules, and milk lipid composition was modified. Moreover, the gene expression dynamic from virgin to pregnancy state resulted in the identification of about 3000 differentially expressed genes specific to SOCS2KI/KI or control mice. Our results show that SOCS2 is important for mammary gland development and milk production. In the long term, this finding raises the possibility of ensuring adequate milk production without compromising animal health and welfare.
The present study proposes to measure and quantify the heart rate variability (HRV) changes during effort as a function of the heart rate and to test the capacity of the produced indices to predict ...cardiorespiratory fitness measures. Therefore, the beat-to-beat cardiac time interval series of 18 adolescent athletes (15.2 ± 2.0 years) measured during maximal graded effort test were detrended using a dynamical first-order differential equation model. HRV was then calculated as the standard deviation of the detrended RR intervals (SDRR) within successive windows of one minute. The variation of this measure of HRV during exercise is properly fitted by an exponential decrease of the heart rate: the SDRR is divided by 2 every increase of heart rate of 20 beats/min. The HR increase necessary to divide by 2 the HRV is linearly inversely correlated with the maximum oxygen consumption (r = -0.60, p = 0.006), the maximal aerobic power (r = -0.62, p = 0.006), and, to a lesser extent, to the power at the ventilatory thresholds (r = -0.53, p = 0.02 and r = -0.47, p = 0.05 for the first and second threshold). It indicates that the decrease of the HRV when the heart rate increases is faster among athletes with better fitness. This analysis, based only on cardiac measurements, provides a promising tool for the study of cardiac measurements generated by portable devices.
High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal ...strategy of ventilation to avoid reintubation.
To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU.
Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018.
Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen alternating with NIV (n = 342) immediately after extubation.
The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality.
Among 648 patients who were randomized (mean SD age, 70 10 years; 219 women 34%), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% 95% CI, -12.0% to -0.9%; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% 95% CI, -15.2% to -1.8%; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% 95% CI, -13.2% to -1.8%; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% 95% CI, -6.7% to 1.7%; P = .25).
In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone.
ClinicalTrials.gov Identifier: NCT03121482.
We previously showed that the homeodomain transcription factor HOXB9 is expressed in mammalian oocytes and early embryos. However, a systematic and exhaustive study of the localization of the HOXB9 ...protein, and HOX proteins in general, during mammalian early embryonic development has so far never been performed.
The distribution of HOXB9 proteins in oocytes and the early embryo was characterized by immunofluorescence from the immature oocyte stage to the peri-gastrulation period in both the mouse and the bovine. HOXB9 was detected at all studied stages with a dynamic expression pattern. Its distribution was well conserved between the two species until the blastocyst stage and was mainly nuclear. From that stage on, trophoblastic cells always showed a strong nuclear staining, while the inner cell mass and the derived cell lines showed important dynamic variations both in staining intensity and in intra-cellular localization. Indeed, HOXB9 appeared to be progressively downregulated in epiblast cells and only reappeared after gastrulation had well progressed. The protein was also detected in the primitive endoderm and its derivatives with a distinctive presence in apical vacuoles of mouse visceral endoderm cells.
Together, these results could suggest the existence of unsuspected functions for HOXB9 during early embryonic development in mammals.
Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients.
...We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen.
analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI).
Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m
), 204 (33%) were overweight (25 kg/m
⩽ BMI < 30 kg/m
), and 213 (34%) were normal or underweight (BMI < 25 kg/m
). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (
= 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% 95% confidence interval, -19 to -6;
= 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% 95% confidence interval, -11 to -2;
= 0.006).
Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).
The aim of this work was to study the effect of a sustained activation of AMP-activated protein kinase (AMPK) on liver cell survival. AMPK activation was achieved by incubating FTO2B cells with ...AICA-riboside, which is transformed into ZMP, an AMP analogue, or by adenoviral transfection of hepatocytes with a constitutively active form of AMPK. Prolonged AMPK activation triggered apoptosis and activated c-Jun N-terminal kinase (JNK) and caspase-3. Experiments with iodotubercidin, dicoumarol and z-VAD-fmk, which inhibited AMPK, JNK and caspase activation, respectively, supported the notion that prolonged AMPK activation in liver cells induces apoptosis through an activation pathway that involves JNK and caspase-3.
Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional ...study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974.
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