A 41-year-old woman was admitted with hemorrhagic shock with abdominal and right flank pain four days after undergoing cesarean delivery. Contrast-enhanced computed tomography revealed a large retroperitoneal hematoma. Angiography showed a ruptured right ovarian artery aneurysm, anastomosing with a dilated uterine artery. She was successfully treated with transcatheter arterial embolization.

A research topic was launched to solve a current engineering problem: the design of a 3D printing device/equipment for the implementation of additive technology. This device shall be adapted on a numerically controlled machine, CNC TMA-AL-550, for dual operation under a milling machine or the printing equipment control. During the development of the research topic solution, several errors related to the functionality of the equipment and the control of the advance of the deposition material occurred. The decision adopted was, without a doubt, the most efficient and handy, namely, the application of the finite element analysis method (FEA), in two phases: 1)-analysis of heat transfer; 2)-analysis of the state of stresses and strains, for which the exact discretization in finite element mesh was used. The FEA method was developed using ANSYS® 2021 R1 software. This procedure included solving the mathematical model developed for the FEA method by connecting two analysis systems: the ANSYS ® Steady-State Thermal system and the ANSYS ®-Static Structural system. Thus we managed to achieve the transfer, very quickly, of the nodal temperatures from the heat transfer analysis system (ANSYS ® Steady-State Thermal system) to the analysis system of the stress state and deformations of the solid (ANSYS®-Static Structural system-"Thermal stresses").

Bryophytes’ remarkable capacity to tolerate extreme abiotic conditions allows us to enhance our understanding of the diversity of molecular mechanisms involved in plant stress response. Here, we used next generation sequencing to study DNA methylation and gene expression changes in plants from four populations of the metallophyte moss Scopelophila cataractae experimentally exposed to either Cd or Cu. These populations previously showed differences in tolerance to both metals, so here, we aimed at uncovering the molecular basis of this phenotypic differentiation. We found no evidence of genetic differentiation among the populations studied. The epigenetic data, however, showed limited but significant population-specific changes in DNA methylation in response to both metals. Exposure to acute Cu stress in the laboratory led to the downregulation of genes involved in heavy metal tolerance in both populations regardless of their tolerance level, but this response was quantitatively higher in the most tolerant. We propose that chronic exposure to varying levels of heavy metals in the field led to potentially non-genetically-based intraspecific differentiation for heavy metal tolerance in S. cataractae. The most tolerant plants invested more in constitutive protection and were more efficient in entering a conservative state when faced with acute Cu stress.

Aims: Voriconazole is the mainstay for the treatment for invasive fungal infections in heart transplant patients and significantly increase tacrolimus exposure because of drug-drug interaction (DDI). However, the magnitude of this DDI is highly variable and hard to predicted. The purpose of this study was to present the characteristics of DDI between tacrolimus and voriconazole, and further identify the predictors of tacrolimus dose modification. Methods: We retrospectively enrolled 69 heart transplant recipients without using voriconazole as the control and 68 patients received voriconazole treatment in voriconazole group. CYP3A4*1G, CYP3A5*3 and CYP2C19*2 or *3 were genotyped by Sanger sequencing. The requirement of tacrolimus dose for therapeutic concentrations and tacrolimus dose-corrected trough concentration (C0/D) before and after VRC administration were evaluated. Results: The DDI between tacrolimus and voriconazole was in a large inter-individual variability with more than ten-fold changes in tacrolimus dose (range 1.28–13.00) and C0/D (range 1.43–13.75). Besides, the fold changes of tacrolimus dose were associated with CYP2C19 genotype, which was significantly lower in CYP2C19 extensive metabolizers than that in CYP2C19 intermediate metabolizers or poor metabolizers (4.06±1.85 vs 5.49±2.47, p=0.0031). While no significant difference was found in both CYP3A4 and CYP3A5 genotypes. Moreover, CYP2C19 genotype and hematocrit were independent predicting factors for tacrolimus dose modification after voriconazole co-therapy. Conclusions: This study provided a potential basis for comprehensive factors to adjust tacrolimus dosage when co-administrated with voriconazole in individual patients. CYP2C19 genotype and hematocrit should be considered in tailoring tacrolimus dose.

Aims: This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF). Methods: We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up. Results: Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P=0.013). The ABCB1 SNP rs4148738 was associated with major bleeding events in the addictive model (P=0.046, OR=3.29) and dominant model (P=0.040, OR=8.17). Additionally, the ABCB1 SNP rs1045642 was associated with the incidence of major bleeding events in the addictive model (P=0.043, OR=3.34) and dominant model (P=0.046, OR=7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events. Conclusions: Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.

Objective To examine the association of DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in stillborn fetuses. Design A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study. Setting Multicenter, 59 hospitals in 5 geographic regions in the USA. Population 387 stillbirth cases (2006-2008). Methods Using standard definitions, PPLs were categorized by type including maternal and fetal vascular, inflammatory and immune/idiopathic lesions. Using single-nucleotide polymorphism array, CNVs of at least 500 kb were detected. CNVs were classified into two groups: normal, defined as no CNVs>500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. Main outcome measures The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without PPLs using the Wald Chi-squared test. Results Of 387 stillborn fetuses, 327 (84.5%) had maternal vascular PPLs and 60 (15.6%) had abnormal CNVs. Maternal vascular PPLs were more common in stillborn fetuses with abnormal CNVs compared with those with normal CNVs (81.7% vs. 64.2%; p=0.008). The proportions of fetal vascular, maternal/fetal inflammatory, and immune/idiopathic PPLs were similar among stillborn fetuses with abnormal CNVs compared to those with normal CNVs. Pathogenic CNVs in stillborn fetuses with maternal vascular PPLs spanned several genes with known relevant mechanisms. Conclusions Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillborn fetuses. Findings may provide insight on the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.

Background: Children should be weaned from the ventilator once their clinical condition improves. Extubation failure is associated with poorer clinical outcomes in children. Predictive indicators of successful extubation are needed. This study aims to evaluate the predictive value of ultrasonographic diaphragm imaging could help predict weaning success. Methods: In this prospective, observational study conducted between March and December 2021, children between 1 month and 10 years of age who were mechanically ventilated for more than 48 hours were included. Diaphragm ultrasound (DUS) examinations were performed at the end of 2-hour extubation readiness test (ERT). The end-inspiratory thickness, end-expiratory thickness, diaphragmatic thickening fraction, diaphragmatic excursion, inspiratory slope and expiratory slope were evaluated. Results: Twenty-four (60%) patients were successfully extubated, while 16 (40%) required invasive or non-invasive mechanical ventilation support which were classified as failed extubation group. Three of the sixteen patients in the failed extubation group required re-intubation. Diaphragm thickening fraction was significantly greater in the successful weaning group (55,05 ± 23,75% vs. 30,9 ± 10,38%) (p<0,001). Diaphragm excursion was significantly greater in the SW group (14 ± 4,4 mm vs 11,05 ± 3,25 mm) (p<0,001). DTF and DE were found to have a sensitivity and specificity of 91.67 %, 87.50 %, and 83.33 %, 81.25 %, respectively. Conclusion: Diaphragm ultrasound is a feasible and promising tool to guide physicians during weaning from IMV. Among all DUS measurements, the DE and DTF indexes showed better performance in extubation failure than other diaphragmatic parameters.

For defining the optimal machine learning algorithm, the decision was not easy for which we shall choose. To help future researchers, we describe in this paper the optimal among the best of the algorithms. We built a synthetic data set and performed the supervised machine learning runs for five different algorithms. For heterogeneous rock fabric, we identified Random Forest, among others, to be the appropriate algorithm.

Idiopathic Thrombocytopenia and Splenomegaly are two well known pathologies that often can be managed medically. However there are instances in which surgical management is indicated. We report the proper management of a young man with splenomegaly and hypersplenism refractory to medical treatment with a history of Idiopathic Thrombocytopenia.

This paper investigates the three dimensional tropic climate equations with fractional diffusion and nonlinear damping. The global exixtence and unique strong solutions of the tropic climate equations have been build under the assumption that initial data $(u_0,v_0,\theta_0)\in H^1(\R^3)\times H^1(\R^3)\times H^1(\R^3)$ with $\alpha>1, \max(1,\frac{p+4}{2p})<\beta, \gamma<1+\frac{3}{p+1}$ and $p,q > 3$.

LETTER TO THE EDITOR

Background Children with tracheostomies are at an increased risk of bacterial respiratory tract infections. Infections caused by multidrug-resistant organisms (MDROs) are more difficult to treat and can result in severe complications. We investigated the risk factors and sequelae of MDRO positivity in tracheostomy and chronic ventilator-dependent children. Methods We performed a retrospective chart review of 75 tracheostomy and chronic ventilator-dependent children at St. Louis Children’s Hospital. Data on demographics, respiratory cultures, hospitalizations, emergency department (ED) visits, and antibiotic usage were collected. We determined the frequency of MDRO positivity and compared the number of hospitalizations, number of ED visits, and antibiotic usage in patients with and without MDRO-positive cultures. Patient clinical variables were analyzed before and after MDRO acquisition. Results We found 75.7% (56/74) of our participants had an MDRO-positive culture, with methicillin-resistant Staphylococcus aureus (MRSA, n=36, 64%) and Pseudomonas aeruginosa (n=8, 14%) being the most commonly detected organisms. Patients with MDRO-positive cultures had a greater number of annual non-pulmonary admissions [OR=1.99, 95% CI (1.21-3.29), P= 0.008], inpatient antibiotic courses [OR=1.27, 95% CI (1.07-1.50), P=0.006], total antibiotic courses [OR=1.26, 95% CI (1.08-1.48), P= 0.004], and chronic antibiotic use [OR=2.31, 95% CI (1.12-4.74), P=0.03] compared to MDRO-negative participants. Patients that acquired MDROs during the study period subsequently required increased outpatient antibiotics [P= 0.006] but did not have increased pulmonary admissions or ED visits. Conclusion Frequent antibiotic usage and hospitalizations increase the risk of MDRO acquisition in children with tracheostomies and ventilator-dependence. Further antibiotic stewardship may help prevent resistant infections in technology-dependent children.

Aim: Pregnant women are hypothesized to have low adherence to prescribed medication, because of concerns about toxicity and harmful effects on the unborn child. However, very little is known about the actual adherence to prescribed medication during pregnancy. We determined to what extent women follow treatment recommendations regarding prescribed medication use in mid-pregnancy. Methods: Dutch women participating in the PRIDE Study completed a six-week diary on medication use. Additionally, pharmacy records were obtained. For each medication dispensed, we determined three measures of adherence: 1) whether use was reported in the diary (actual use), 2) difference between dispensing date and date of first reported use (initiation time), and 3) proportion of days with at least the correct number of doses taken (implementation adherence). Results: During the six-weeks study period, 235 of 816 women (29%) were prescribed medication. Actual use was highest for medications used for chronic conditions (88%; 95% confidence interval [95% CI] 81-93), followed by medication for pregnancy-related conditions (79%; 95% CI 71-86) and medication for occasional and short-time use (69%; 95% CI 60-77). We observed a ≥1 day delay in treatment initiation for 42% of medications dispensed for the first time in the study period. For medications that were actually used, mean implementation adherence was 74.2% (95% CI 69.3-79.2). Conclusion: Although actual use of medications dispensed was high, many pregnant women did not adhere to treatment recommendations. This non-adherence may impact maternal and child health and lead to exposure misclassification in studies in perinatal pharmacoepidemiology relying on administrative databases.

Objective: To study the association between mode of conception and risk of preterm birth (PTB), including, spontaneous and provide-initiated PTB. Design: Retrospective cohort study Setting and Population: Population-based cohort included all singleton livebirths and stillbirth in Ontario, Canada, 2006-2014. Methods: Mode of conception comprised (i) subfertility without infertility treatment (N = 68,822); (ii) non-invasive infertility treatment (ovulation induction +/- intrauterine insemination) (N = 9024); or (iii) Invasive infertility treatment (in vitro fertilization [N = 8038) – each compared to births by unassisted conception (N = 646,926). Modified Poisson regression generated risk ratios (RR). Confounding was handled by inverse probability of treatment weighting using a propensity that included maternal demographics and pre-existing conditions. Main Outcome Measure: PTB < 37 completed weeks’ gestation. PTB was further categorized as spontaneous PTB or provider-initiated PTB. Results: PTB occurred among 6.0% of births by unassisted conception, 7.7% with subfertility, 8.0% with non-invasive infertility treatment, and 10.8% following invasive infertility treatment. The RR of provider-initiated PTB was higher in women with subfertility (RR 1.23, 95% CI 1.16-1.31), non-invasive infertility treatment (RR 1.48, 1.29-1.69) and invasive infertility treatment (RR 2.35, 2.09-2.64) – each relative to births by unassisted conception. The corresponding RR for spontaneous PTB were 1.15 (95% CI 1.10-1.19), 1.19 (95% CI 1.09-1.31) and 1.40 (95% CI 1.27-1.53). Conclusions: Subfertility, and receipt of infertility treatment, are each associated with a higher risk of PTB, especially provider-initiated PTB. Strategies are needed to reduce the underlying indications to deliver these women before term.

This Supporting information includes supporting fugures and videos for our paper.  The information's Fig. 16 is the high-quality version of the article's Supplementary Movie 1.Corresponding author(s) Email:   nakashima@robot.t.u-tokyo.ac.jp  

Acute gastric volvulus is a rare yet life threatening condition with mortality ranging from 30% to 50% if not treated promptly. The stomach rotates on itself, causing strangulation precipitating necrosis, cameron lesions and perforation. Long-standing paraesophageal hernia is a common cause of organoaxial gastric volvulus.

Subacute combined degeneration (SACD) of the spinal cord is a common neurological manifestation of vitamin B12 deficiency. We report a rare finding of hyperintense T2 signal in the dorsal and lateral columns with restricted diffusion in MR study of the thoracic spine in 47 years old diagnosed with SACD.

Transverse myelitis can be a complication of SARS-CoV-2 infection. We report the case of transverse myelitis related to SARS-CoV-2 infection. Beyond the disease itself, neurological involvement affects functionality. In this situation, Physical and Rehabilitation Medicine plays a crucial role in managing patient rehabilitation.

Aim: This systematic review aims to assess the safety profile of oxcarbazepine during pregnancy. Methods: Observational studies that included women who took oxcarbazepine anytime during pregnancy were included in our systematic review. The review did not include non-English articles, reviews, meta-analyses, case reports, and animal studies. Different online sources such as MEDLINE, Cochrane library, Virtual Health library etc. were searched for published and unpublished literature. Assessment of risk of bias of observational studies was done using the Newcastle-Ottawa Scale. The meta-analyses were performed using a random-effect model. GRADE was used for the evaluation of the quality of evidence for the primary outcomes. Results: We included 19 cohort studies with a total number of 5,071,137 patients, of which 2,450 were exposed to oxcarbazepine either as monotherapy or polytherapy. The summary odds ratio (OR) was 1.69 (95% CI, 0.95-2.98) for congenital malformations following in-utero exposure to oxcarbazepine as compared to the control group of unexposed patients [seven studies (n=625)], and was 1.19 (95% CI, 0.67-2.12) when compared to those following lamotrigine (LTG) exposure during pregnancy [3 studies (n=591)]. In total, three studies (n=770) reported the association between in-utero oxcarbazepine exposure and fetal/perinatal deaths. The meta-analysis yielded a summary OR of 3.11 (95% CI, 0.57-16.97). Significance: Our systematic review will help healthcare providers and guideline developers regarding the treatment of epilepsy and other neurological disorders during pregnancy. More cohort studies with a higher sample size concerning oxcarbazepine use in pregnant patients are required to truly assess the in-utero safety profile of the drug.

Cor-Knot device is an automated suture fastening system which was introduced to minimize the operating time during cardiac surgery. It is currently being used for intracardiac suturing applications such as implanting valves or rings during aortic and mitral valve surgery primarily for shortening the procedure time. It also has higher holding pressures and more consistent holding pressures than manual knots. We describe here the use of Cor-Knot device in extracardiac suturing to secure aortic root vent as well as aortic cannulation during minimally invasive cardiac surgery. A 60-year-old male with mitral valve endocarditis underwent minimally invasive mitral valve replacement via right mini thoracotomy. Direct ascending aortic cannulation was performed through a separate port. Cor-Knots were successfully used to secure the purse-string sutures after decannulation at the end of the case.

Lipoma is a common benign soft tissue tumor. we report a 33-year-old patient with a giant lipoma in the left scapular region. We placed a self-made rubber drainage strip during the operation to control exudate, which is effective in improving incision effusion and worthy of clinical promotion.

A 71-year-old woman was admitted to the hospital due to cardiac tamponade. Computed tomography revealed that the diameter and wall thickness of the ascending aorta was 36 mm and 9 mm, respectively. An emergency surgery was performed uneventfully. The pathological findings indicated frank rupture of intramural hematoma.

The current study aims to find suitable fatigue assessment methods for welded structures (cover plates and T-joints) subjected to axial and bending loading. For this purpose, the Hot Spot Stress method (HSS), 1-mm stress (OM) method, Theory of Critical Distances (TCD) method, Stress Averaging (SA) method, and Effective Notch Stress (ENS) method are evaluated in terms of accuracy and reliability. The evaluation is based on fatigue test data extracted from the literature and fatigue testing carried out in the current study; cover plate joints subjected to axial loading and T-joints subjected to bending. The notch stress methods have higher estimation accuracy for the cover plate joints subjected to axial loading than the structural stress methods. It is found that the SA method can be used to assess the fatigue strength of cover plate joints with good accuracy and low scatter, followed by the ENS method. The fatigue strength assessment of T-joints subjected to bending using the HSS method, TCD method, SA method, and ENS method and corresponding FAT class is conservative, whilst the accuracy is low. Fatigue design curves applicable for T-joints under bending are introduced and described, which can be used in the TCD method, SA method, and ENS method.

Aim: Chirality of drugs might be associated with safety issues through pharmacokinetic or pharmacodynamic variations, interactions, or direct toxicological responses. This study aimed to examine chiral status of the drugs withdrawn from the market. Methods: We searched the literature regarding withdrawn drugs between 1950-2020 due to safety-related issues and identified 395 drugs. We examined their chirality and assigned into one of three categories: achiral compound, chiral mixture, and pure enantiomer. We compared their distribution at ATC-1 level, duration on the market, and adverse drug reactions leading to their withdrawal. Results: We identified that 52.4% (n=207) of withdrawn drugs were achiral, whereas 27.6% (n=109) were chiral mixtures and 20.0% (n=79) were pure enantiomers. The mean duration on the market was 24.6±27.5 years. The groups did not differ in terms of mean duration on the market. Chiral mixtures were significantly more withdrawn than were achirals in cardiovascular system drugs (17.4% vs. 7.7%, p=0.01). In musculoskeletal system drugs, pure enantiomers were significantly less withdrawn (2.5%) compared to achirals (12.6%, p=0.01) and chiral mixtures (11.9%, p=0.03). Hepatotoxicity was significantly less common in pure enantiomers (5.4%) compared to chiral mixtures (12.7%, p=0.04) and achirals (17.0%, p<0.01). Cardiovascular toxicity was significantly more common in chiral mixtures (14.5%) compared to that in achiral drugs (7.5%, p=0.02). Conclusion: Our study showed slightly higher representation of chiral mixtures among withdrawn drugs over pure enantiomers. The assessment of withdrawal reasons further indicates higher tendency of chiral mixtures towards hepatotoxicity and cardiovascular toxicity.