Transformation of theranostic alginate-based microbubbles from raspberry-like to core-shell-like microbubbles and in vitro studies.

In this study alginate-based microbubbles with a raspberry-like or core-shell-like morphology and with an average particle size of 553.6 ± 69.6 µm were synthesized; this was done through a novel procedure of transforming the structure with a 40 kHz ultrasonication which also stimulated the release of the components inside. Through the use of the electrospray technique in conjunction with agitation processes, components such as shikonin (SHK) and indocyanine green (ICG) were simultaneously encapsulated in alginate microbubbles to produce SHK-ICG alginate microbubbles; these microbubbles had half-maximal inhibitory concentrations of approximately 2.08 and 4.43 µM toward CP70 and SKOV3 ovarian cancer-cell lines, respectively, in an in vitro cell model. Moreover, these SHK-ICG alginate microbubbles enhanced brightness by 2.5 fold in ultrasound imaging relative to CaCl2 medium only. In conclusion, SHK-ICG alginate microbubbles have promise for use in theranostics.

Investigating the Effects of Different Sizes of Silicone Rubber Vacuum Extractors during the Course of Delivery on the Fetal Head: A Finite Element Analysis Study.

During certain clinical situations, some parturients require instruments for operative vaginal delivery, and various designs of vacuum extractors may affect the fetal head. To investigate the biomechanical effects of divergent sizes of silicone rubber vacuum extractors, we employed finite element analysis in this study. First, we constructed computer models for different vacuum extractor sizes (diameters: 40 mm, 50 mm, 60 mm, and 70 mm), flat surface, hemispherical ball, and fetal head shape. A hemispherical ball was the main design for the vacuum extractor model, and the material used for the vacuum extractor was silicone rubber. Next, the settings of 1 mm vacuum extractor displacement and vacuum cap pressure of 60 cmHg were applied. The main observation markers of this study were the respective von Mises stresses on the vacuum extractor and skull by the reaction force on the fixed end. The concluded results revealed that vacuum extractors with larger diameters lead to greater reaction force, stress, and strain on fetal heads. Therefore, this study's biomechanical analytic consequences suggest that clinicians avoid selecting larger vacuum extractors during operative instrumental delivery so that fetal heads will experience less external force, deformation, and resultant complications. It could also provide a practical reference for obstetricians for instrumental vaginal delivery with the vacuum extractor made of silicone rubber.

The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Severe acute respiratory syndrome coronavirus-2 and the deduction effect of angiotensin-converting enzyme 2 in pregnancy.

The 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) is a pandemic disease worldwide. The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is continuing at a rapid speed. Till May 4, 2020, there have been 3,407,747 confirmed cases and 238,198 deaths globally. The common symptoms in pregnant women are fever, cough, and dyspnea. Angiotensin-converting enzyme 2 (ACE2) has transient overexpression and increased activity during pregnancy, which is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. There is no evidence that pregnant women are more susceptible to SARS-CoV-2. To date, there is no valid medication or vaccination. The immune suppression or modulation during pregnancy increases the risk of severe pneumonia. Remdesivir is an antiviral medication targeting ribonucleic acid (RNA) synthesis that has clinical improvement in the treatment of SARS-CoV-2. Chloroquine is controversial in its effectiveness and safety to treat SARS-CoV-2. Remdesivir is safe in pregnancy. Chloroquine has not been formally assigned to a pregnancy category by the Food and Drug Administration (FDA). The management strategy includes monitoring fetal heart rate and uterine contractions; early oxygenation if O2 saturation is less than 95%; empiric antibiotics for prevention of secondary infection; corticosteroid to treat maternal SARS-CoV-2 disease routinely is not suggested, only for fetal lung maturation in selected cases; and consideration of delivery is according to the obstetric indication, gestational age, and severity of the disease. During epidemics, delivery at 32-34 weeks is considered. The indication for the Cesarean section should be flexible to minimize the risk of infection during the delivery. The newborn should be in isolation ward immediately after birth; breastfeeding is not contraindicated but should avoid direct transmission infection.

Pyruvate Kinase M2 Expression: A Potential Metabolic Biomarker to Differentiate Endometrial Precancer and Cancer That Is Associated with Poor Outcomes in Endometrial Carcinoma.

BACKGROUND: Pyruvate kinase M2 (PKM2) is a regulator of the processes of glycolysis and oxidative phosphorylation, but the roles that it plays in endometrial cancer remain largely unknown. This study evaluated the PKM2 expression in normal endometrium, endometrial hyperplasia, and endometrial carcinoma, and its prognostic value was investigated in endometrial carcinoma patients. METHODS: A hospital-based retrospective review was conducted to examine the immunohistochemical PKM2 distribution in 206 endometrium samples from biopsies or hysterectomies. The immunoreactivity of PKM2 was divided into groups of low and high scores according to the extent and intensity of staining. RESULTS: Intense cytoplasmic staining was observed for the PKM2 protein in malignant endometrial lesions. A high PKM2 score was observed in many endometrial carcinoma samples (50.0%), but there was a low percentage in endometrial atypical hyperplasia (12.5%). High PKM2 expression was not found in the normal endometrium (0.0%) nor endometrial hyperplasia without atypia (0.0%). The PKM2 protein score was significantly higher in endometrial carcinoma samples than premalignant endometrial lesions (p < 0.001). Notably, higher PKM2 scores in cases of endometrial carcinoma correlated with poor overall survival (p = 0.006), and the hazard ratio for death was 3.40 (95% confidence interval, 1.35-8.56). CONCLUSIONS: Our results indicate that the prevalence of PKM2high tumor cells in endometrial carcinoma is significantly associated with worse prognostic factors and favors a poor prognosis. The expression of PKM2 is also a potential histopathological biomarker for use in the differential diagnosis of malignant and premalignant endometrial lesions.

Successful treatment with granulocyte-colony stimulating factor for ritodrine-induced neutropenia in a twin pregnancy.

OBJECTIVE: Neutropenia developed after continuous intravenous infusion of ritodrine hydrochloride (Yutopar) for preterm uterine contractions in a twin pregnancy. We successfully returned the low neutrophil count to the normal range after discontinuation of infusion of ritodrine and treatment with granulocyte colony stimulating factor (G-CSF). CASE REPORT: A 34-year-old woman with twin pregnancy was treated with ritodrine for preterm uterine contractions at 27 weeks and 6 days gestation. Neutropenia developed after continuous intravenous infusion of ritodrine for about 4 weeks. We ceased the ritodrine infusion immediately and treated the neutropenia with G-CSF. A cesarean delivery was performed the day after cessation of the ritodrine infusion because of uncontrolled preterm labor. There were no adverse side effects or infectious complications in the mother or the newborns. The maternal neutrophil count recovered to the normal range 4 days after administration of G-CSF. CONCLUSION: Based on prior case reports and the clinical presentation of our case, G-CSF may be a useful treatment for pregnant women with ritodrine-induced neutropenia. However, more clinical studies are required to confirm the safety and efficacy of this treatment.

Pregnancy in a noncommunicating rudimentary horn of a unicornuate uterus: Prerupture diagnosis and management.

OBJECTIVE: The estimated incidence of rudimentary horn pregnancy is one in 76,000. It is a life-threatening entity with a 50% risk of uterine rupture. With advances in prenatal ultrasound in recent decades, there may be an opportunity to detect rudimentary horn pregnancy earlier, resulting in a lower incidence of maternal morbidity and mortality. Management is typically resection of the rudimentary horn and the ipsilateral fallopian tube by either laparotomy or laparoscopy. CASE REPORT: Here, we present the case of a 22-year-old woman with a suspected ectopic pregnancy of 12 weeks' gestation. Ultrasound and magnetic resonance imaging were performed as preoperative evaluations. A definitive diagnosis was made during laparotomy, and resection of the rudimentary horn pregnancy was performed. CONCLUSION: Diagnosis and management of rudimentary horn pregnancy remain a challenge. We should be alert to prenatal ultrasound with the intention of making an earlier diagnosis, thereby resulting in decreased maternal morbidity and mortality.

Cardiac arrest during emergency cesarean section for severe pre-eclampsia and peripartum cardiomyopathy.

OBJECTIVE: To present the correlation between severe pre-eclampsia and peripartum cardiomyopathy in pregnancy. CASE REPORT: A 41-year-old parturient, gravida 3, para 1, at 34 4/7 weeks' gestation, was diagnosed with severe pre-eclampsia. At the time of admission, a plain chest film disclosed bilateral pleural effusions. An emergent cesarean section was planned because of decreased fetal movement, heavy daily protein loss, and bilateral pleural effusions. During the cesarean section, she developed shock with acute respiratory failure. She underwent advanced cardiac life support and intubation with mechanical ventilator support. Peripartum cardiomyopathy was subsequently diagnosed by echocardiography. CONCLUSION: The presented case demonstrates that routine echocardiography is highly recommended for suspected peripartum cardiomyopathy in gravidas with severe pre-eclampsia and symptoms or signs of heart failure.

Gestational choriocarcinoma with renal and pulmonary metastases lacking a primary uterine origin.

OBJECTIVE: We describe a case of gestational choriocarcinoma metastasized to the kidney and lung, which presented initially as refractory hematuria after a term pregnancy 5 years earlier. CASE REPORT: A 35-year-old woman, G2P1, with a previous history of full-term pregnancy in 2009, presented to the emergency department complaining of intermittent gross hematuria for 2 months. Abdominal computed tomography showed a suspicious arteriovenous malformation in the right kidney and a thrombus within the right renal vein. Transarterial embolization was performed twice to treat the refractory hematuria but was unsuccessful, and radical nephrectomy of the right kidney was performed. The diagnosis was gestational metastatic choriocarcinoma of the kidney based on morphological, immunohistochemical, and DNA studies. Lung metastases were found by computed tomography of the chest. Pelvic ultrasound was performed but showed no primary tumor in the uterine cavity. After surgical intervention, adjuvant chemotherapy involving first single-agent chemotherapy with methotrexate followed by multiagent chemotherapy (EMACO regimen) failed. CONCLUSION: In women of reproductive age, unexplained hematuria should raise concerns about possible choriocarcinoma, either metastatic gestational or primary nongestational choriocarcinoma of the kidney.

Prenatal diagnosis of a de novo 9p terminal chromosomal deletion in a fetus with major congenital anomalies.

OBJECTIVE: We describe a prenatal ultrasonography diagnosis of omphalocele and symbrachydactyly in a fetus and review the literature on prenatal diagnosis of 9p terminal chromosomal deletions. CASE REPORT: A 31-year-old woman (gravida 3, para 1) was referred for genetic counseling because a fetal omphalocele had been detected. Prenatal ultrasonography at 17+ weeks of gestational age revealed a singleton female fetus with biometry equivalent to 18 weeks with an omphalocele. In addition, symbrachydactyly was also noted in the right arm; the wrist bones as well as the metacarpals were missing. A chromosomal study was arranged for a congenital anomaly involving omphalocele. We obtained Giemsa-banded chromosomes from fetal tissue cells, and an abnormal male karyotype with a terminal deletion of the short arm of chromosome 9 at band 9p13 was noted. After delivery, the fetus showed omphalocele, symbrachydactyly, trigonocephaly, sex reversal, a long philtrum, low-set ears, telecanthus, and a frontal prominence. CONCLUSION: Prenatal diagnosis of abnormal ultrasound findings with omphalocele and symbrachydactyly should include the differential diagnosis of a chromosome 9p deletion.