Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Longitudinal multi-omics of host-microbe dynamics in prediabetes.

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

Robust identification of temporal biomarkers in longitudinal omics studies.

MOTIVATION: Longitudinal studies increasingly collect rich 'omics' data sampled frequently over time and across large cohorts to capture dynamic health fluctuations and disease transitions. However, the generation of longitudinal omics data has preceded the development of analysis tools that can efficiently extract insights from such data. In particular, there is a need for statistical frameworks that can identify not only which omics features are differentially regulated between groups but also over what time intervals. Additionally, longitudinal omics data may have inconsistencies, including non-uniform sampling intervals, missing data points, subject dropout and differing numbers of samples per subject. RESULTS: In this work, we developed OmicsLonDA, a statistical method that provides robust identification of time intervals of temporal omics biomarkers. OmicsLonDA is based on a semi-parametric approach, in which we use smoothing splines to model longitudinal data and infer significant time intervals of omics features based on an empirical distribution constructed through a permutation procedure. We benchmarked OmicsLonDA on five simulated datasets with diverse temporal patterns, and the method showed specificity greater than 0.99 and sensitivity greater than 0.87. Applying OmicsLonDA to the iPOP cohort revealed temporal patterns of genes, proteins, metabolites and microbes that are differentially regulated in male versus female subjects following a respiratory infection. In addition, we applied OmicsLonDA to a longitudinal multi-omics dataset of pregnant women with and without preeclampsia, and OmicsLonDA identified potential lipid markers that are temporally significantly different between the two groups. AVAILABILITY AND IMPLEMENTATION: We provide an open-source R package (https://bioconductor.org/packages/OmicsLonDA), to enable widespread use. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Diagnostic accuracy of ultrasound in the diagnosis of Placenta accreta spectrum: systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of ultrasound and in the diagnosis of Placenta accreta spectrum (PAS). DATA SOURCES: Screening of MEDLINE, CENTRAL, other bases from inception to February 2022 using the keywords related to placenta accreta, increta, percreta, morbidly adherent placenta, and preoperative ultrasound diagnosis. STUDY ELIGIBILITY CRITERIA: All available studies- whether were prospective or retrospective- including cohort, case control and cross sectional that involved prenatal diagnosis of PAS using 2D or 3D ultrasound with subsequent pathological confirmation postnatal were included. Fifty-four studies included 5307 women fulfilled the inclusion criteria, PAS was confirmed in 2025 of them. STUDY APPRAISAL AND SYNTHESIS METHODS: Extracted data included settings of the study, study type, sample size, participants characteristics and their inclusion and exclusion criteria, Type and site of placenta previa, Type and timing of imaging technique (2D, and 3D), severity of PAS, sensitivity and specificity of individual ultrasound criteria and overall sensitivity and specificity. RESULTS: The overall sensitivity was 0.8703, specificity was 0.8634 with -0.2348 negative correlation between them. The estimate of Odd ratio, negative likelihood ratio and positive likelihood ratio were 34.225, 0.155 and 4.990 respectively. The overall estimates of loss of retroplacental clear zone sensitivity and specificity were 0.820 and 0.898 respectively with 0.129 negative correlation. The overall estimates of myometrial thinning, loss of retroplacental clear zone, the presence of bridging vessels, placental lacunae, bladder wall interruption, exophytic mass, and uterovesical hypervascularity sensitivities were 0.763, 0.780, 0.659, 0.785, 0.455, 0.218 and 0.513 while specificities were 0.890, 0.884, 0.928, 0.809, 0.975, 0.865 and 0.994 respectively. CONCLUSIONS: The accuracy of ultrasound in diagnosis of PAS among women with low lying or placenta previa with previous cesarean section scars is high and recommended in all suspected cases. TRIAL REGISTRATION: Number CRD42021267501.

The effect of music intervention in decreasing pain and anxiety during outpatient hysteroscopy procedure: a systematic review and meta-analysis of randomized control trials.

BACKGROUND: Hysteroscopy is a common outpatient procedure but procedural pain limits its use. Music could be used as a pain-relieving intervention. We performed a systematic review and meta-analysis to investigate the effect of music on pain and anxiety during outpatient hysteroscopy. METHODS: Four electronic databases were searched: PubMed, Scopus, Web of Science, and Cochrane Library, from inception to September 2022. We included only the Randomized Controlled Trials (RCTs) that investigated the effect of music on women who underwent outpatient hysteroscopy in reducing pain and anxiety levels compared to no music. We assessed the quality of included RCTs using the risk of bias tool 1 reported in the Cochrane Handbook of Systematic Reviews of Interventions. Data were pooled as the Mean Differences (MDs) with a 95% Confidence Interval (CI) in a random-effects model, using Review Manager 5.3 software. Also, we assessed the evidence of the results using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Three RCTs (540 women) were included. Music significantly reduced visual analogue scale (VAS) pain scores as well as State-Trait Anxiety Inventory (STAI) scores compared to controls (MD = -1.28; 95% CI [-2.19, -0.36]; P = 0.007) and (MD = -3.91; 95% CI [-6.98, -0.85]; P = 0.01) respectively. Also, the decrease in VAS score for pain was significantly greater in the music group (MD = 1.44; 95% CI [0.44, 2.45]; P = 0.005). However, the change in STAI showed no significant difference between the two groups. The GRADE ratings for all outcomes were very low. CONCLUSION: Music is a potentially promising method for controlling pain for patients undergoing outpatient hysteroscopy; however, its effect in controlling anxiety is controversial.

The value of platelet-rich plasma in women with previous implantation failure: a systematic review and meta-analysis.

OBJECTIVE: To assess the value of intrauterine PRP to improve IVF outcome in women with previous implantation failure. METHODS: Screening of Pubmed, Web of Science, and other databases from inception to August 2022 using the keywords related to "platelet-rich plasma" OR "PRP" AND "IVF" "implantation failure." Twenty-nine studies (3308 participants) were included in our analysis, 13 were RCTs, 6 were prospective cohorts, 4 were prospective single arm, and 6 were retrospective analyses. Extracted data included settings of the study, study type, sample size, participants' characteristics, route, volume, timing of PRP administration, and outcome parameters. RESULTS: Implantation rate was reported in 6 RCTs (886 participants) and 4 non-RCTs (732 participants). The odds ratio (OR) effect estimate was 2.62 and 2.06, with 95% CI of 1.83, 3.76, and 1.03-4.11, respectively. Endometrial thickness was compared in 4 RCTs (307 participants) and 9 non-RCTs (675 participants), which showed a mean difference of 0.93 and 1.16, with 0.59-1.27 and 0.68-1.65 95% CI, respectively. CONCLUSION: PRP administration improves implantation, clinical pregnancy, chemical pregnancy, ongoing pregnancy, live birth rates, and endometrial thickness in women with previous implantation failure.

Detection and quantification of perioperative heparin-like effects by rotational thromboelastometry in living-donor liver transplant recipients: A prospective observational study.

Background and Aims: Heparin-like effects (HLEs) can affect hemostasis during liver transplantation. The aim of this study was to assess the perioperative incidence and severity of HLE with rotational thromboelastometry (ROTEM) and activated partial thromboplastin time (aPTT). Material and Methods: ROTEM and aPTT were measured intraoperatively and on postoperative days (POD) 1, 3, and 7. HLE was identified if ROTEM INTEM/HEPTEM CT-ratio was >1.25 and severe forms of HLE when ratio was ≥2. Based on aPTT, HLE was defined when aPTT ratio was >1.25 (patient aPTT/control aPTT). Results: Thirty-eight recipients were included. Variable degrees of HLE were detected by aPTT-ratio and INTEM/HEPTEM CT ratio. No significant correlation existed between both ratios. Based on INTEM/HEPTEM CT ratio, HLE was detected in 7/38 during anhepatic phase, 19/38 post-reperfusion, 10/38 on POD1, 4/38 on POD3, and 0/38 on POD7. Four cases of severe HLE were identified by INTEM/HEPTEM CT ratio only in the anhepatic phase. Postoperative infusion of unfractionated heparin led to mild-moderate HLE on POD1 and 3 as evident by both tests. Red blood cell and plasma transfusion were higher with severe HLE (1350 ± 191 ml and 3558 ± 1407 ml). Composite adverse outcome of any complication or death within 3 months for patients without HLE, mild-moderate HLE, and severe HLE as detected by ROTEM was 27.8%, 42.9%, and 66.7%, respectively. Conclusion: INTEM/HEPTEM CT ratio was able to detect and quantify HLE as aPTT ratio. The ability of the INTEM/HEPTEM CT ratio to identify severe HLE earlier in the anhepatic phase needs to be studied in a larger population. HLE is self-limiting, but when identified in a severe form, it is associated with worse outcome.

The efficacy of misoprostol in reducing intraoperative blood loss in women undergoing elective cesarean section. A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy of misoprostol to minimized blood loss during and after cesarean delivery (CD). SEARCH STRATEGY: Screening of MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials from inception to February 2021 using the keywords related to misoprostol, CD, postpartum hemorrhage, and intraoperative blood loss and their MeSH terms. SELECTION CRITERIA: Only RCTs were included. Participants included women undergoing CD whether elective or selective. Thirty studies including 6593 women, 26 in English, 2 in Thai, 1 in French, and 1 in Chinese. DATA COLLECTION AND ANALYSIS: Data from all selected studies were extracted independently by two authors. Data extracted included location of the trial, sample size, inclusion and exclusion criteria, participants characteristics, intervention details including timing, dose, and route of drug administration. Outcomes assessed included estimated intraoperative and postoperative blood loss, occurrence of postpartum hemorrhage, the need for additional uterotonics, and hemoglobin difference. MAIN RESULTS: Four studies (968 women) compared preoperative to postoperative misoprostol and found a mean difference in intraoperative blood loss of -205.00 (-339.22, -70.77), p = 0.003 and in postoperative blood loss -216.27 (-347.08, -85.46), p < 0.001 and a significantly lower need for additional uterotonics with a risk ratio of 0.54 (0.46, 0.64), p < 0.00001. Twenty-two studies (4701 participants) compared misoprostol to oxytocin. There was a mean difference in intraoperative blood loss of -108.43 (-156.04, -60.82), p < 0.0001. Nine of these trials with 1978 participants evaluated postoperative blood loss. These found a mean difference of -64.12 (-116.19, -12.04) with a p = 0.02. Fourteen trials with 3166 participants measured the difference between preoperative and postoperative hemoglobin. These found a mean difference of -0.25 (-0.35, -0.15) with a p < 0.001. Twenty trials with 4416 participants measured the need for administration of additional uterotonics. These found a risk ratio of 0.62 (0.49, 0.78) with a p value of <0.001. CONCLUSION: The combined use of misoprostol and oxytocin during CD is effective in reducing blood loss during and after CD.

Black soldier fly (Hermetia illucens) larvae meal in diets of European seabass: Effects on antioxidative capacity, non-specific immunity, transcriptomic responses, and resistance to the challenge with Vibrio alginolyticus.

Black soldier fly larvae meal (BSFLM) has been successfully demonstrated as a promising fish meal (FM) replacer in diets of several fish species including European seabass (Dicentrarchus labrax). However, its impacts on antioxidant capacity, and immune responses of treated fish are still poorly understood. A 60-day feeding trial was carried out to evaluate the effects of partial substitution of FM with different levels of dry BSFLM on the antioxidative status, non-specific immunity, transcriptomic responses, and resistance of European seabass to the challenge with Vibrio alginolyticus. Four isoproteic (45%) and isolipidic diets were formulated by replacing 0.0%, 25%, 35%, and 50% of the dietary FM. Each diet was randomly assigned to four fish groups (in triplicates) (initial mean body weight, 12.1 ± 0.21 g) (20 fish per aquarium) (n = 240). Fish were fed three times daily to the apparent satiation. At the end of the feeding trial, serum antioxidant biomarkers such as malondialdehyde levels, and catalase, superoxide dismutase, and glutathione peroxidase enzyme activities were significantly increased in all BSFLM groups in a dose-dependent manner compared to the control group (P < 0.05). The non-specific immune indices, including phagocytic activity, phagocytic index, serum lysozyme and respiratory burst activities were significantly elevated in BSFLM groups compared to those in the control group (P < 0.05). Significant upregulation of the mRNA expression levels of hepatic heat shock protein 70, interleukin-1beta and interleukin-10 genes were observed in all BSFLM groups compared to the control group (P < 0.05). Additionally, after the challenge with V. alginolyticus, the relative percent of survival was significantly elevated in fish groups fed on diets containing graded levels of BSFLM over the control group (P < 0.05). Conclusively, the present study suggests the potential efficacy of partial replacement of dietary FM protein for up to 50% by BSFLM without negative effects on fish health with possible potentiation of the antioxidative status, and the immune responses of the European seabass.

Early detection of SARS-CoV-2 and other infections in solid organ transplant recipients and household members using wearable devices.

The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.

Reliability Analysis of the New Exponential Inverted Topp-Leone Distribution with Applications.

The inverted Topp-Leone distribution is a new, appealing model for reliability analysis. In this paper, a new distribution, named new exponential inverted Topp-Leone (NEITL) is presented, which adds an extra shape parameter to the inverted Topp-Leone distribution. The graphical representations of its density, survival, and hazard rate functions are provided. The following properties are explored: quantile function, mixture representation, entropies, moments, and stress-strength reliability. We plotted the skewness and kurtosis measures of the proposed model based on the quantiles. Three different estimation procedures are suggested to estimate the distribution parameters, reliability, and hazard rate functions, along with their confidence intervals. Additionally, stress-strength reliability estimators for the NEITL model were obtained. To illustrate the findings of the paper, two real datasets on engineering and medical fields have been analyzed.

Effect of average volume-assured pressure support treatment on health-related quality of life in COPD patients with chronic hypercapnic respiratory failure: a randomized trial.

The long-term effect of average volume-assured pressure support (AVAPS) on health-related quality of life (HRQOL) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure (CHRF) remains unclear. The objective of this study is to identify the long-term effect of AVAPS in COPD patients with CHRF through assessment of HRQOL, exercise tolerance after six months duration. METHODS: In this randomized, controlled, parallel-group study, 40 stable hypercapnic COPD patients were randomized in a 1:1 ratio to receive either spontaneous timed AVAPS (ST/AVAPS) (intervention) or Bilevel positive airway pressure (ST/BiPAP) (control). HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12). Exercise tolerance assessed by 6 min walking distance. Analyses were done between groups from baseline to the average of six months measurements. RESULTS: AVAPS led to significant 6 months improvements in several domains of (SF-12) compared to the control group, with the greatest improvement seen in general health [treatment effect of 8.2 points (95% confidence interval [95% CI 3.2 to 11.7; p = 0.001)], vitality (treatment effect 5.4 points [95% CI 1.4 to 9.3]; p = 0.001), physical functioning 5.5 points [95% CI 1.1 to 9.8]; p = 0.001) and bodily pain 5.1 points [95% CI 3.4 to 8.8]; p = 0.002). The physical health summary score improved by 3.7 points (95% CI 1.2 to 5.8; p = 0.001), but no significant improvement in the emotional or social role functioning, mental health subscale was noted. AVAPS also resulted in improvement 6 min walking distance 9.2 points (95% CI - 1 to - 15];p = 0.001). A significant reduction in the daytime (PaCO2) was observed after 6 months in those treated with AVAPS. CONCLUSIONS: In COPD patients with hypercapnic respiratory failure, AVAPS improved exercise tolerance and multiple domains of HRQOL over six months of follow-up, with the significant improvement observed in general health.

Utilizing longitudinal microbiome taxonomic profiles to predict food allergy via Long Short-Term Memory networks.

Food allergy is usually difficult to diagnose in early life, and the inability to diagnose patients with atopic diseases at an early age may lead to severe complications. Numerous studies have suggested an association between the infant gut microbiome and development of allergy. In this work, we investigated the capacity of Long Short-Term Memory (LSTM) networks to predict food allergies in early life (0-3 years) from subjects' longitudinal gut microbiome profiles. Using the DIABIMMUNE dataset, we show an increase in predictive power using our model compared to Hidden Markov Model, Multi-Layer Perceptron Neural Network, Support Vector Machine, Random Forest, and LASSO regression. We further evaluated whether the training of LSTM networks benefits from reduced representations of microbial features. We considered sparse autoencoder for extraction of potential latent representations in addition to standard feature selection procedures based on Minimum Redundancy Maximum Relevance (mRMR) and variance prior to the training of LSTM networks. The comprehensive evaluation reveals that LSTM networks with the mRMR selected features achieve significantly better performance compared to the other tested machine learning models.

Vaginal Dinoprostone in Reducing Pain Perception During Diagnostic Office Hysteroscopy in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY OBJECTIVE: To evaluate the efficacy of vaginal dinoprostone in reducing pain perception during diagnostic office hysteroscopy (OH) in postmenopausal women. DESIGN: Randomized, double-blind controlled trial. SETTING: Tertiary university hospital. PARTICIPANTS: Postmenopausal patients scheduled for OH. INTERVENTIONS: Eligible participants were randomized in a 1:1 ratio to the dinoprostone and placebo groups. The severity of pain was assessed with a visual analog scale (VAS) ranging from 0, no pain to 10, worst pain during OH and 30 minutes after OH. MEASUREMENTS AND MAIN RESULTS: The difference in the intensity of pain using the VAS score during the procedure. One hundred women (50 in each arm) were included in the study. The mean VAS score during OH was significantly lower in the dinoprostone group compared with the placebo group (3.9 ± 0.8 vs 5.6 ± 0.7; p <.001). The passage of the hysteroscope through the cervical canal was easier in the dinoprostone group (62.4 ± 9.5 vs 42.8 ± 10.8; p <.001). The 2 groups were comparable in terms of the duration of the procedure (p = .91) and the rate of adverse effects. CONCLUSION: Vaginal dinoprostone is effective in relieving pain during diagnostic OH in postmenopausal women with few adverse effects.

Benefits of vaginal dinoprostone administration prior to levonorgestrel-releasing intrauterine system insertion in women delivered only by elective cesarean section: a randomized double-blinded clinical trial.

PURPOSE: This study aimed at investigating the efficacy and safety of dinoprostone 3 mg vaginally prior to levonorgestrel-releasing intrauterine system (LNG-IUS) insertion in women undergoing elective cesarean delivery (CD). METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled trial at family planning clinic of Cairo University hospitals from August 2019 to January 2020. We included 200 women aged ≥ 18 years who previously delivered by elective CD willing to receive LNG-IUS. Women were randomly assigned with a 1:1 allocation ratio to receive 3 mg vaginal dinoprostone or placebo tablets two hours before LNG-IUS insertion. Our main outcomes were patient-reported pain during insertion and 30 min post-procedure, ease of insertion, satisfaction, duration of insertion, and different side effects. RESULTS: Patient-perceived pain during LNG-IUS insertion was significantly reduced in dinoprostone compared to placebo (4.1 ± 1.7 vs 6.4 ± 1.3; p < 0.001). Dinoprostone reduced pain scores 30 min post-procedure compared to placebo, but the difference was not statistically significant (3.5 ± 1.1 vs 3.7 ± 1.6; p = 0.25). Satisfaction score was higher in dinoprostone compared to placebo (7.9 ± 1.0 vs 5.9 ± 0.8; p < 0.001). The insertion was significantly easier and shorter in dinoprostone than placebo (3.9 ± 1.1 vs 5.9 ± 1.1; p < 0.001) and (5.6 ± 0.9 vs 7.2 ± 0.8; p < 0.001), respectively. Adverse events were not significantly different between both groups. CONCLUSION: Dinoprostone administration 2 h before LNG-IUS insertion in women delivered by elective CD effectively reduced pain during insertion and 30 min post-procedure. Women received dinoprostone had easier and shorter insertion and were more satisfied with tolerable side effects.

Role of Oral Tramadol 50 mg in Reducing Pain During Colposcopy-Directed Cervical Biopsy: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to assess safety and efficacy of 50-mg tramadol in reducing patient-perceived pain during colposcopy. MATERIAL AND METHODS: We conducted a randomized double-blind placebo-controlled trial in the colposcopy unit of a tertiary referral hospital, Cairo, Egypt, from April 2018 to October 2018. Our primary outcome was pain during colposcopy-guided ectocervical punch biopsy. Our secondary outcomes were pain during speculum insertion, acetic acid application, Lugol iodine application, endocervical curettage (ECC), endocervical brushing, 10-minute postprocedure, and additional analgesia requirement. Pain was assessed using 10-cm visual analog scale. RESULTS: One hundred fifty women were randomized into 2 groups: tramadol group (n = 75) received oral 50-mg tramadol tablets, and control group (n = 75) received placebo tablets. Both groups showed no significant difference in anticipated pain score (p = .56), pain scores during speculum insertion (p = .70), application of acetic acid (p = .40), and Lugol iodine (p = .79). However, the mean pain scores were significantly lower in tramadol group compared with placebo at ectocervical biopsy (p = .001), ECC (p = .001), endocervical brushing (p = .001), and 10 minutes after colposcopy (p = .001). Need for additional analgesia was significantly lower in tramadol group (p = .03). CONCLUSIONS: Oral tramadol 50 mg significantly reduces pain perception during colposcopy-guided ectocervical biopsy, ECC, endocervical brushing, and 10 minutes after colposcopy with tolerable adverse effects.

Kirschner Wires Versus Titanium Plates and Screws in Management of Unstable Phalangeal Fractures: A Randomized, Controlled Clinical Trial.

PURPOSE: To compare clinical, radiological and functional outcomes of percutaneous K-wires and lateral titanium plates and screws in the management of unstable extra-articular proximal and middle phalangeal fractures. METHODS: In a randomized controlled clinical trial, 40 patients with unstable transverse, long oblique or spiral diaphyseal fractures of the proximal and middle phalanges were divided into 2 groups: the K-wire group (20 patients), which included 12 proximal and 8 middle phalangeal fractures fixed by percutaneous K-wires; and the plate group (20 patients), which included 13 proximal and 7 middle phalangeal fractures treated with open reduction and internal fixation with a lateral titanium plate and screws. The patients were observed for at least 6 months (mean [range], 6.9 [6-8] months). Results were evaluated by total active motion (TAM), grip strength, fracture union, pain assessed by visual analog scale and the Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire, and complications. RESULTS: Clinical and radiological union was achieved in all patients except one in the K-wire group. Mean TAM was significantly better in the plate group than in the K-wire group. Both groups were similar in terms of postoperative loss of grip strength compared with the opposite healthy hand, and as assessed by visual analog scale and the Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire. Fewer complications occurred in the plate group (2 of 20 patients) compared with the K-wire group (5 of 20 patients). CONCLUSIONS: Fixation of unstable proximal and middle phalangeal fractures using a titanium plate and screws through a midlateral approach is a reliable and safe method for most fracture types and is associated with higher TAM and fewer complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

A Circulating MicroRNA Signature Serves as a Diagnostic and Prognostic Indicator in Sarcoidosis.

MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression. In sarcoidosis, aberrant miRNA expression may enhance immune responses mounted against an unknown antigenic agent. We tested whether a distinct miRNA signature functions as a diagnostic biomarker and explored its role as an immune modulator in sarcoidosis. The expression of miRNAs in peripheral blood mononuclear cells from subjects who met clinical and histopathologic criteria for sarcoidosis was compared with that observed in matched controls in the ACCESS (A Case Controlled Etiologic Study of Sarcoidosis) study. Signature miRNAs were determined by miRNA microarray analysis and validated by quantitative RT-PCR. Microarray analysis identified 54 mature, human feature miRNAs that were differentially expressed between the groups. Significant feature miRNAs that distinguished subjects with sarcoidosis from controls were selected by means of probabilistic models adjusted for clinical variables. Eight signature miRNAs were chosen to verify the diagnosis of sarcoidosis in a validation cohort, and distinguished subjects with sarcoidosis from controls with a positive predictive value of 88%. We identified both novel and previously described genes and molecular pathways associated with sarcoidosis as targets of these signature miRNAs. Additionally, we demonstrate that signature miRNAs (hsa-miR-150-3p and hsa-miR-342-5p) are significantly associated with reduced lymphocytes and airflow limitations, both of which are known markers of a poor prognosis. Together, these findings suggest that a circulating miRNA signature serves as a noninvasive biomarker that supports the diagnosis of sarcoidosis. Future studies will test the miRNA signature as a prognostication tool to identify unfavorable changes associated with poor clinical outcomes in sarcoidosis.

Dobutamine and Nitroglycerin Versus Milrinone for Perioperative Management of Pulmonary Hypertension in Mitral Valve Surgery. A Randomized Controlled Study.

OBJECTIVE: To compare the effects of dobutamine and nitroglycerin to milrinone in young patients with severe pulmonary hypertension undergoing mitral valve replacement. DESIGN: A prospective randomized, double-blinded, controlled study. SETTING: Single university hospital. PARTICIPANTS: Forty patients had systolic pulmonary arterial pressure ≥60 mmHg and were scheduled for elective mitral valve replacement. The patients were divided randomly into 2 equal groups according to the drugs given during the study. INTERVENTIONS: The patients in group I received 5 to 20 µg/kg/min of dobutamine and 0.5 to 3 µg/kg/min of nitroglycerin, and patients in group II received a loading dose of milrinone, 50 µg/kg over 10 minutes, followed by a maintenance dose of 0.25 to 0.75 µg/kg/min. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the effects of interventional drugs on mean pulmonary artery pressure. The secondary outcomes were the effects of interventional drugs on systemic and pulmonary hemodynamic parameters measured from induction of anesthesia until the first 12 hours in the intensive care unit stay. There was a more significant decrease in mean pulmonary artery pressure, pulmonary capillary wedge pressure, and central venous pressure in group II than group I at all time points after cardiopulmonary bypass. There were more significant increases in heart rate, mean arterial pressure, cardiac output, and mixed venous oxygen tension in group I than group II, which became more obvious in time. In both groups, there was a significant decrease in systemic vascular resistance and pulmonary vascular resistance at all times. CONCLUSION: Milrinone provides adequate cardiac performance, causing a greater reduction in pulmonary artery pressure and pulmonary capillary wedge pressure.

Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: A randomised double-blinded trial.

BACKGROUND: During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE: To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN: A randomised, double-blind, controlled study. SETTING: Single University Hospital. PATIENTS: Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS: The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 µg kg over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 µg kg h dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES: The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS: At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION: Administration of dexmedetomidine in doses 0.4 and 0.6 µg kg h was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org).