Background:
Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients.
Objectives:
...The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS.
Methods:
Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire.
Results:
After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire.
Conclusion:
This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD.
In the last years, enormous progress has been made in the analysis of gene transcription at the blastocyst stage. The study of gene expression at this early stage of development is challenging ...because of the very small amount of starting material, which limits the use of traditional mRNA analysis approaches such as Northern blot. Another problem is the difficulty for data normalization, particularly the identification of the best housekeeping gene with the lowest fluctuation under different developmental conditions. Moreover, the transcriptional analysis of embryo biopsies or individual embryos needs to take into consideration that the blastocyst is a transitional stage of development, which is composed of three different types of cells (trophoblast, epiblast and primitive ectoderm) with different patterns of gene expression, and that there are large differences between male and female blastocysts. In this review, we analyse the different specific and sensitive tools available to compare mRNA expression levels of specific genes at the blastocyst stage, and how the protocol and the analytical method used can influence the results dramatically. Finally, we describe future research challenges to identify candidate genes related to developmental competence of bovine blastocysts, not only in terms of pregnancy rates but also in relation to adverse long‐term consequences in the adult animal.
In the last years, enormous progress has been made in the analysis of gene transcription at the blastocyst stage. The study of gene expression at this early stage of development is challenging ...because of the very small amount of starting material, which limits the use of traditional mRNA analysis approaches such as Northern blot. Another problem is the difficulty for data normalization, particularly the identification of the best housekeeping gene with the lowest fluctuation under different developmental conditions. Moreover, the transcriptional analysis of embryo biopsies or individual embryos needs to take into consideration that the blastocyst is a transitional stage of development, which is composed of three different types of cells (trophoblast, epiblast and primitive ectoderm) with different patterns of gene expression, and that there are large differences between male and female blastocysts. In this review, we analyse the different specific and sensitive tools available to compare mRNA expression levels of specific genes at the blastocyst stage, and how the protocol and the analytical method used can influence the results dramatically. Finally, we describe future research challenges to identify candidate genes related to developmental competence of bovine blastocysts, not only in terms of pregnancy rates but also in relation to adverse long-term consequences in the adult animal. PUBLICATION ABSTRACT
BACKGROUND: Thiamine deficiency has been associated with poorer clinical outcomes. Early recognition of thiamine deficiency is difficult in critically ill patients because clinical signs are ...nonspecific. OBJECTIVE: We determined the prevalence of and identified risk factors associated with low blood thiamine concentrations upon admission of children to a pediatric intensive care unit and evaluated this condition as a predictor of clinical outcomes. DESIGN: A prospective cohort study was conducted in 202 children who had whole-blood thiamin concentrations assessed by HPLC upon admission to the intensive care unit. The following independent variables for thiamine deficiency were analyzed: age, sex, nutritional status, clinical severity scores upon admission (ie, the revised Pediatric Index of Mortality and Pediatric Logistic Organ Dysfunction score), systemic inflammatory response measured by C-reactive protein serum concentrations, severe sepsis or septic shock, heart failure, and cardiac surgery. The dependent variables in the outcome analyses were mortality, length of stay, and time on mechanical ventilation. RESULTS: Low blood thiamine concentrations upon admission were detected in 57 patients (28.2%) and were shown to be independently associated with C-reactive protein concentrations >20 mg/dL (odds ratio: 2.17; 95% CI: 1.13, 4.17; P = 0.02) but not with malnutrition. No significant association was shown between low blood thiamine concentrations upon admission and outcome variables. CONCLUSIONS: The incidence of low blood thiamine concentrations upon admission was high. Of the risk factors examined, only the magnitude of the systemic inflammatory response showed an independent association with this event. The association between thiamine deficiency upon admission and prognosis requires further investigation.
•Thiamine deficiency is an underrecognized and potentially lethal disorder.•There is an interaction between blood thiamine and malnutrition on the risk of mortality.•Blood thiamine concentration has ...a protective effect on the risk of mortality only in malnourished patients.•The patient's nutritional status should be considered in trials on thiamine supplementation.
To test the hypothesis that low blood thiamine concentrations in malnourished critically ill children are associated with higher risk of 30-d mortality.
Prospective cohort study in 202 consecutively admitted children who had whole blood thiamine concentrations assessed on admission and on days 5 and 10 of intensive care unit (ICU) stay. The primary outcome variable was 30-d mortality. Mean blood thiamine concentrations within the first 10 d of ICU stay, age, sex, malnutrition, C-reactive protein concentration, Pediatric Index of Mortality 2 score, and severe sepsis/septic shock were the main potential exposure variables for outcome.
Thiamine deficiency was detected in 61 patients within the first 10 d of ICU stay, 57 cases being diagnosed on admission and 4 new cases on the 5th d. C-reactive protein concentration during ICU stay was independently associated with decreased blood thiamine concentrations (P = 0.003). There was a significant statistical interaction between mean blood thiamine concentrations and malnutrition on the risk of 30-d mortality (P = 0.002). In an adjusted analysis, mean blood thiamine concentrations were associated with a decrease in the mortality risk in malnourished patients (odds ratio = 0.85; 95% confidence interval CI: 0.73–0.98; P = 0.029), whereas no effect was noted for well-nourished patients (odds ratio: 1.03; 95% CI: 0.94–1.13; P = 0.46).
Blood thiamine concentration probably has a protective effect on the risk of 30-d mortality in malnourished patients but not in those who were well nourished.
The presence of pharmaceuticals in the aquatic environment and its impact on humans and the ecosystem are emerging issues in environmental health. This study evaluated the potential biochemical, ...genetic and reproductive effects of the diclofenac by waterborne exposure, in a semi-static bioassay for 21 days. The fish Rhamdia quelen were exposed to environmental concentrations of diclofenac (0, 0.2, 2 and 20µg/L). The results showed that in the liver, diclofenac reduced the catalase and ethoxyresorufin- O- deethylase activities in fish exposed to 2µg/L, and superoxide dismutase in all exposed groups. The levels of reduced glutathione and glutathione S-transferase (GST) activity increased at all tested concentrations. Lipid peroxidation (LPO) was reduced in the groups exposed to 0.2 and 20µg/L of diclofenac, but there was no protein oxidation. In the testis, the concentration of 0.2µg/L caused major changes as inhibition of SOD, glutathione peroxidase and GST activities and also LPO decrease. Diclofenac was not genotoxic and not altered plasma testosterone and estradiol levels and testicular morphology. In brain, there was a reduction of dopamine and its metabolite DOPAC (3, 4-dihydroxyphenylacetic acid) in exposure to diclofenac, but this not disrupted the hypothalamic-pituitary-gonadal axis.
•Rhamdia quelen were exposed to diclofenac for 21 days.•Diclofenac affected hepatic and gonadal antioxidant defenses in Rhamdia quelen.•Diclofenac was not genotoxic.•Diclofenac exposure reduced dopamine and its metabolite DOPAC.•Diclofenac in the environment may have negative impacts in aquatic organisms.
Chemotherapy (QT) is a systemic treatment using a combination of antineoplastic drugs, orally or intravenously, that inhibit tumor growth and fast-growing normal cells. Due to its nonspecificity, ...chemotherapy can cause a series of adverse effects, such as altered taste (dysgeusia), associated with malnutrition and, consequently, other adverse effects in the gastrointestinal tract and increased mortality risk. This study aimed to evaluate the influence of dysgeusia on the incidence of other adverse effects and overall survival during antineoplastic chemotherapy (chemotherapy).
An observational, retrospective, cross-sectional study was conducted using data from the Electronic Health Record system of the Cancer Institute of Ceará over two years. Before the CT session, the multi-professional team evaluated the patient for the presence and severity of adverse effects (AE), using scores from the CTCAE v5.0 scale. Dysgeusia scores were collected and associated with clinical pathological data, with other adverse effects (nausea, vomiting, diarrhea, oral mucositis, anorexia, constipation), and with overall survival. Chi-square and Mantel-Cox log-rank tests were used.
Of 5744 patients evaluated, dysgeusia presented a frequency of 50.6%, being directly associated with female gender (p=0.001), overweight (p=0.022), high tumor stages (p=0.009), a combination of adjuvant and neoadjuvant (p=0.010) and four-year survival (p=0.030). Dysgeusia frequency was directly associated with diarrhea (p<0.001), anorexia (p<0.001), oral mucositis (p<0.001), nausea (p<0.001), constipation (p<0.001) and vomiting (p<0.001), and inversely associated with fatigue (p=0.035).
Dysgeusia during CT increases the risk of other adverse effects and negatively impacts prognosis.
The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear.
To evaluate the effectiveness of an evidence-based, goal-directed checklist in the ...clinical management of brain-dead potential donors in the intensive care unit (ICU).
The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020.
Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care.
The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group.
Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 57.1%), followed by trauma (485 31.6%). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 48.4% brain-dead potential donors) and 32 (50.8%) to the control group (792 51.6% brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio RR, 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006).
This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist.
ClinicalTrials.gov Identifier: NCT03179020.
Summary Background Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 ( PMP22 ), a model of Charcot–Marie–Tooth disease type 1A (CMT1A) ...associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Methods Adult patients (aged 18–70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 ( CMT-TRAUK ) and EudraCT 2006-000032-27 ( CMT-TRI AA L ). Findings We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the ascorbic acid group and 13·9 (4·2) in the placebo group. Mean worsening of CMTNS was 0·2 (SD 2·8, 95% CI −0·3 to 0·7) in the ascorbic acid group and 0·2 (2·7, −0·2 to 0·7) in the placebo group (mean difference 0·0, 95% CI −0·6 to 0·7; p=0·93). We recorded no differences between the groups for the secondary outcomes at 24 months. 21 serious adverse events occurred in 20 patients, eight in the ascorbic acid group and 13 in the placebo group. Interpretation Ascorbic acid supplementation had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence is available to support treatment with ascorbic acid in adults with CMT1A. Funding Telethon-UILDM and AIFA (Italian Medicines Agency) for CMT-TRI AA L, and Muscular Dystrophy Campaign for CMT-TRAUK.
Background: Thiamine deficiency has been associated with poorer clinical outcomes. Early recognition of thiamine deficiency is difficult in critically ill patients because clinical signs are ...nonspecific.
Objective: We determined the prevalence of and identified risk factors associated with low blood thiamine concentrations upon admission of children to a pediatric intensive care unit and evaluated this condition as a predictor of clinical outcomes.
Design: A prospective cohort study was conducted in 202 children who had whole-blood thiamin concentrations assessed by HPLC upon admission to the intensive care unit. The following independent variables for thiamine deficiency were analyzed: age, sex, nutritional status, clinical severity scores upon admission (ie, the revised Pediatric Index of Mortality and Pediatric Logistic Organ Dysfunction score), systemic inflammatory response measured by C-reactive protein serum concentrations, severe sepsis or septic shock, heart failure, and cardiac surgery. The dependent variables in the outcome analyses were mortality, length of stay, and time on mechanical ventilation.
Results: Low blood thiamine concentrations upon admission were detected in 57 patients (28.2%) and were shown to be independently associated with C-reactive protein concentrations >20 mg/dL (odds ratio: 2.17; 95% CI: 1.13, 4.17; P = 0.02) but not with malnutrition. No significant association was shown between low blood thiamine concentrations upon admission and outcome variables.
Conclusions: The incidence of low blood thiamine concentrations upon admission was high. Of the risk factors examined, only the magnitude of the systemic inflammatory response showed an independent association with this event. The association between thiamine deficiency upon admission and prognosis requires further investigation.
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