Role of Amyloid Beta in Neurodegeneration and Therapeutic Strategies for Neuroprotection.

The gradual loss of neurons' structure and function in the central nervous system is known as neurodegeneration. It is a defining feature of several incapacitating illnesses, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The buildup of amyloid beta (Aß) protein in the brain is one of the several variables linked to neurodegeneration. We shall delve into the fascinating realm of Aß in this chapter and examine its role in the etiology of neurodegenerative illnesses. Insights into the processes through which Aß exerts its toxicity are crucial for the creation of therapeutic approaches to treat these life-threatening diseases. Despite the presence of multiple obstacles, recent research shows promise for the development of some new anti-Aß therapies that will help millions of people suffering from neurodegeneration. In this chapter, we discuss the role of Aß in contributing to neurotoxicity and several anti-Aß therapies for neuroprotection.

Novel approach to prenatal predictors of outcomes for fetuses with severe Ebstein anomaly.

OBJECTIVE: Ebstein anomaly (EA) is a cardiac malformation with highly variable presentation and severity with limited perinatal management options. We present incorporation of fetal lung measurements into a multidisciplinary evaluation for counseling and predicting postnatal outcomes in patients with severe EA. METHODS: Five fetuses with severe fetal EA were reviewed. Third trimester sonographic observed/expected total lung area (O/E TLA) and lung to head ratio (O/E LHR), fetal MRI total fetal lung volume ratio (O/E-TFLV), echocardiographic cardio-thoracic ratio (CT ratio), sonographic estimated fetal weight (EFW) by Hadlock formula and presence of hydrops, were used to guide perinatal management. RESULTS: Three of five had appropriate fetal growth, were delivered at term in a cardiac operative suite, and underwent immediate intervention with good neonatal outcomes. Two had severe fetal growth restriction (FGR), CT ratios > 0.8 and O/E LHR and TLA < 25%. One of which delivered prematurely with neonatal demise and one suffered in utero demise at 34 weeks. CONCLUSIONS: FGR, hydrops, increased CT ratio and reduced O/E LHR and TFLV are potential prognosticators of poor outcomes in severe EA, and should be validated in larger cohorts that would allow for a statistical analysis of the predictive utility of these measurements.

Pulmonary hypoplasia is associated with severe morbidityThere are limited prognosticating tools to risk stratify and guide management in cases of severe prenatal Ebstein anomaliesFetal MRI may improve prognostication for fetuses with EA.

Preeclampsia and the Kidney: Pathophysiology and Clinical Implications.

Preeclampsia and other hypertensive disorders of pregnancy are major contributors to maternal morbidity and mortality worldwide. This group of disorders includes chronic hypertension, gestational hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia. The body undergoes important physiological changes during pregnancy to allow for normal placental and fetal development. Several mechanisms have been proposed that may lead to preeclampsia, including abnormal placentation and placental hypoxia, impaired angiogenesis, excessive pro-inflammatory response, immune system imbalance, abnormalities of cellular senescence, alterations in regulation and activity of angiotensin II, and oxidative stress, ultimately resulting in upregulation of multiple mediators of endothelial cell dysfunction leading to maternal disease. The clinical implications of preeclampsia are significant as there are important short-term and long-term health consequences for those affected. Preeclampsia leads to increased risk of preterm delivery and increased morbidity and mortality of both the developing fetus and mother. Preeclampsia also commonly leads to acute kidney injury, and women who experience preeclampsia or another hypertensive disorder of pregnancy are at increased lifetime risk of chronic kidney disease and cardiovascular disease. An understanding of normal pregnancy physiology and the pathophysiology of preeclampsia is essential to develop novel treatment approaches and manage patients with preeclampsia and hypertensive disorders of pregnancy. © 2023 American Physiological Society. Compr Physiol 13:4231-4267, 2023.

Impact of asymptomatic and mild COVID-19 infection on fetal growth during pregnancy.

BACKGROUND: During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR). STUDY DESIGN: This is a single institution, retrospective cohort study of patients ages 16-55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. RESULTS: Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). CONCLUSION: Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.

Obstetric outcomes after fetal intervention - a single-center descriptive review.

BACKGROUND: Advancements in fetal interventions have enabled in utero management of several fetal congenital anomalies and conditions; these are accomplished via ultrasound-guided, fetoscopic or open techniques. Understanding the risk of preterm labor associated with each technique is critical for patient counseling and choice of intervention; however, data on obstetrical outcomes associated with each type of intervention remains limited. OBJECTIVE: To provide descriptive information on the risk of preterm birth following fetal intervention, based on underlying disease and procedure performed. STUDY DESIGN: This is a retrospective cohort study of patients who underwent fetal intervention at our institution between 1 October 2016 and 31 December 2019. Interventions were stratified into three groups- ultrasound-guided, fetoscopic and open procedures. Procedures included fetoscopic laser ablation (FLA) for twin-to-twin transfusion syndrome (TTTS), fetoscopic endotracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH), vesicoamniotic shunt (VAS) for lower urinary tract obstruction (LUTO), fetal cystoscopy for LUTO, and open and fetoscopic myelomeningocele repair. The primary outcomes were gestational age at delivery and frequency of premature rupture of the membranes. RESULTS: Sixty-eight patients were included; 20 (29.4%) underwent ultrasound- guided procedures, 37 (54.4%) underwent fetoscopy, and 11 (16.2%) open in utero intervention. The diagnoses and type of intervention within each group were different. The mean gestational age (GA) ± standard deviation (SD) at intervention for ultrasound- guided, fetoscopic, open procedures were 24.1 ± 4.4 weeks, 22.8 ± 3.7 weeks, and 25.0 ± 0.9 weeks, respectively. The mean GA ± SD at delivery were 31.9 ± 4.9 weeks, 31.6 ± 4.6 weeks, and 32.6 ± 5.5 weeks, respectively. The mean interval from time of intervention to delivery were 54 ± 39, 62 ± 37 and 55 ± 36 days, respectively (p = 0.82); and the risk of PPROM was 26.3%, 21.6% and 27.3%, respectively. The mean GA at delivery and the frequency of PPROM were different for each specific disease that was treated. CONCLUSION: The risk of preterm birth and PPROM following fetal intervention with different procedures, categorized under ultrasound- guided, fetoscopic and open fetal interventions at our institution were similar amongst the three groups, but they were different depending on the diagnosis of the treated anomaly.

Effect of Lockdown Due to COVID-19 on Health and Lifestyle of Psoriasis Patients: A Web-Based Survey.

Background: Chronic skin diseases like psoriasis affect a patient's physical, psychological, and social functioning as well as well-being, and the lockdown acted as a cofactor in further worsening the quality of life in psoriasis patients. Objective: The objective of the study is to assess the effect of lockdown on the health, lifestyle, and mental well-being of psoriasis patients. Methods: A cross-sectional study was done using an online questionnaire shared through messenger applications to the patients of chronic plaque psoriasis who registered in the psoriasis clinic between August 2020 and December 2020. Data regarding demographics, psoriasis, lifestyle changes, mental status, financial loss, and problems faced during lockdown were collected. Results: Our study included 181 completed questionnaires. The mean age was 37.7 (SD 13.9) years, and 124 (68.5%) were males. Sixty-five (35.9%) patients reported worsening of their psoriasis during the lockdown. Ordinal regression analysis revealed male sex had a higher proportion of worsening of psoriasis (OR 2.56, 95% CI 1.29-5.08, P < 0.007). Duration of illness <6 months (OR 0.14, 95% CI 0.02-0.98, P < 0.04) and feeling relaxed (OR 0.14, 95% CI 0.03-0.56, P < 0.005) were negatively associated with disease worsening. Conclusion: The findings of our study reveal the impact of coronavirus disease 2019 (COVID-19) lockdown on the life of people with psoriasis. A substantial number of patients had a flare of psoriasis during the lockdown. A shorter duration of illness and relaxed mental status was negatively associated with disease worsening. Individuals with financial loss felt anxious or depressed.

Intraabdominal pressure as a marker for physiologic and pathologic processes in pregnancy.

Increased intraabdominal pressure (IAP) can result in compression of the abdominal-pelvic venous system leading to signs and symptoms of end organ dysfunction. It has been hypothesized as a pathophysiologic process of preeclampsia. We aim to evaluate the role of IAP in normotensive vs preeclamptic, and singleton vs twin pregnancies. We hypothesized that IAP would be higher in preeclamptics and twins.Women undergoing scheduled cesarean delivery were enrolled in four groups: Singletons- Preeclamptic and Normotensive, Twins- Preeclamptic and Normotensive. Elevated IAP was seen in singleton pregnancies with preeclampsia, representing a pathologic process; and in all twin pregnancies, suggesting a physiologic process.

Sonographic pulmonary response after tracheal occlusion in fetuses with severe isolated congenital diaphragmatic hernia.

PURPOSE: To report the longitudinal lung growth and prognosis of fetuses with severe left sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO) in a single institution. METHODS: Fetal lung size (observed-to-expected lung area to head circumference [o/e-LHR]) was measured in seven consecutive fetuses with isolated severe left-sided CDH who underwent FETO. Fetal lung growth was used to prognosticate survival and need for ECMO. RESULTS: Seven consecutive fetuses had a FETO procedure in the timeframe of this study. A total of 44 longitudinal ultrasound were performed to evaluate lung development. FETO was performed at GA 28.5 ± 0.5 weeks. Five (71.4%) infants survived to one-year follow-up and ECMO was needed in three patients (42.8%). Fetal lung response was observed in all fetuses; mean o/e-LHR increased from 22.5% ± 1.4 before FETO to 44.4% ± 9.8 before delivery. Infants who survived had a higher percentage of fetal lung growth (21.8%) than those who died (8.25%). CONCLUSION: Our study supports the hypothesis that FETO promotes fetal lung growth in fetuses with severe left-sided CDH, and the fetal pulmonary response seems to be associated with improved outcomes after the procedure.

Interventional resealing of preterm premature rupture of the membranes: a systematic review and meta-analysis.

OBJECTIVE: To compare the effectiveness and outcomes of interventional resealing of membranes, "amniopatch" for spontaneous vs. iatrogenic preterm premature rupture of the membranes (sPPROM and iPPROM). METHODS: We performed a systematic review of literature involving an electronic search of the following databases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Scopus. An indirect meta-analysis was then performed to compare the obstetric, maternal, fetal, and neonatal outcomes of amniopatch between the sPPROM and iPPROM groups. RESULTS: The mean gestational age (GA) at the time rupture was 17.8 ± 1.8 and 25.2 ± 3.8 weeks for iPPROM and sPPROM, respectively, p = .005. Mean GA at the time of amniopatch procedure was 19.2 ± 2.07 weeks for iPPROM and 23 ± 3.1 weeks of gestation for sPPROM, p = .023. The rates of fluid re-accumulation (sPPROM 26% and iPPROM 53%, p = .09) were comparable between the sPPROM and iPPROM groups. Neonatal outcomes except for the rate of IUFD were also comparable between the groups. The incidence of IUFD was significantly higher in the iPPROM group (ES: 24%; 95% CI: 8.00-44.0%; p < .001), compared to sPPROM (ES: 0%; 95% CI: 0.00-4.00%). Obstetric and maternal outcomes were comparable between the two groups. CONCLUSIONS: Amniopatch appears to be a feasible and safe procedure for PPROM treatment. Further research is warranted to investigate the effectiveness of this procedure and establish a standardized criterion for the appropriate selection of patients that could benefit from this intervention.

What do we know about the diagnosis and management of mirror syndrome?

INTRODUCTION: Mirror syndrome is a rare disease associated with high fetal mortality of up to 67.2%. It is thought to be underdiagnosed and is often associated with preeclampsia. Mirror syndrome is characterized by "triple edema": generalized maternal, placental, and fetal edema. OBJECTIVE: This comprehensive review aims to thoroughly summarize the existing data and provide a broad update on the topic to help accurate diagnosis and encourage further research. METHODS: A comprehensive search of several databases (Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) was conducted. RESULTS: The last systematic review of mirror syndrome cases was conducted in 2016 and included 113 patients. Much is still unknown about the pathophysiology of the disease and it remains underdiagnosed. CONCLUSIONS AND RELEVANCE: Mirror syndrome is likely more prevalent than current data suggests for it is often misdiagnosed as pre-eclampsia. The differential of Mirror syndrome should be considered in anomalous presentations of pre-eclampsia as intervention may save the fetus and improve maternal symptoms. It is important to further the study on the pathophysiology of the disease to better understand, diagnose and potentially treat it, to avoid its high morbidity and mortality.

Aggregation induced bright organic luminogens: Design strategies, advanced bio-imaging and theranostic applications.

The concept of aggregation-induced emission (AIE) in purely organic luminescent molecules has drawn wide attention in the last two decades. Despite the many challenges, AIE-probes have opened versatile opportunities in many research fields. In particular, the emerging functional properties of room temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) have boosted the unique features of AIE luminogens (AIEgens). Thus, these luminescent materials extended the utility in sensing, imaging, optoelectronics and theranostic applications in biological field over the conventional fluorescent probe. Unlike the sensitivity of triplet state by oxygen and moisture, the long-lived phosphorescence and delayed fluorescence resulting from the enhanced intersystem crossing (ISC) and reverse intersystem crossing (RISC) from excited triplet state (T1) to excited singlet state (S1) in these luminophores gives rise to long lifetimes ranging from nanoseconds to milliseconds even up to seconds. As compared to traditional fluorescence molecules advanced AIE probes show high contrast imaging and deeper penetration depth, which have been demonstrated through near infrared I and II (NIR-I & NIR-II) fluorescence imaging, room temperature after-glow imaging and photoacoustic imaging. This chapter highlights the recent developments and principle of the efficient design of AIE probe with multi-functional properties evolved with new strategies for translational applications via fluorescence imaging, photoacoustic imaging and image-guided photodynamic/photothermal therapy (PDT/PTT) including future opportunities for AIEgens to advance the overall biomedical field.

Management of Complicated Monochorionic Twin Gestations: An Evidence-Based Protocol.

IMPORTANCE: Monochorionic (MC) twins are hemodynamically connected by vascular anastomoses within the single shared placenta. The transfer of fluid or blood from one fetus to the other may result in development of pathologic complications, such as twin-twin transfusion syndrome, twin anemia polycythemia sequence, selective intrauterine growth restriction, and twin reversed arterial perfusion sequence. Monoamniotic gestations, which comprise a small fraction of MC pregnancies, can also present with unique challenges, particularly antepartum umbilical cord entanglement. All these complications carry a high risk of fetal morbidity and mortality if not recognized and managed in a timely fashion. OBJECTIVE: The purpose of this article is to review evidence-based management of complicated MC twin gestations and propose a standardized approach to surveillance. EVIDENCE ACQUISITION: Monochorionic gestations account for the majority of complications that occur in twin pregnancies; however, there is unclear evidence on the appropriate surveillance for and management of specific complications associated with these pregnancies. RESULTS: This article summarizes management for each specific type of MC complication in a structured and clear manner. CONCLUSIONS: Early pregnancy ultrasound, ideally between 10 and 13 weeks' gestation, is critical for the diagnosis and characterization of twin pregnancies. To improve outcomes for MC twins, appropriate fetal surveillance should be initiated at 16 weeks' gestation and continued until delivery.

Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives.

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.

Timing of delivery with coronavirus disease 2019 pneumonia requiring intensive care unit admission.

Approximately 4% of pregnant patients with coronavirus disease 2019 require intensive care unit admission. Given the practical implications of advanced ventilatory and circulatory support techniques, urgent or emergent delivery for nonreassuring fetal status frequently presents a logistical impossibility. This article proposes a protocol for obstetrical management of patients in these situations, emphasizing coordinated preparation among obstetrical, anesthesiology, and intensivist teams for planned preterm delivery at gestational ages when neonatal outcomes are likely to be favorable.

Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia.

Background: Preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome share many clinical and biologic features with thrombotic microangiopathy syndromes caused by complement abnormalities. Our hypothesis was that similar functional and genetic alterations in the complement alternative pathway (CAP) are present in these disorders of pregnancy. Methods: We conducted quantitative analysis of proteins involved in CAP using ELISA and nephelometry on prospectively collected blood samples from patients with severe phenotype preeclampsia (defined as delivery ≤34 weeks due to preeclampsia), HELLP syndrome, or eclampsia, and matched normotensive controls (n=25 in each arm) between 2011 and 2016. Sequencing was performed to interrogate 14 genes encoding CAP components. Results: Both groups were similar in age, gravidity, parity, marital status, and race. The study group had a higher BMI (mean±SD, 32±8 versus 25±4 kg/m2; P=0.002) and earlier gestational age at delivery (32.5±3.6 versus 40.3±1 weeks; P<0.001). Serologic studies demonstrated elevated Bb subunit (median [range], 1.2 [0.5-4.3] versus 0.6 [0.5-1] µg/ml; P<0.001), complement C5 concentration (28 [18-33] versus 24 [15-34] mg/dl; P=0.03), and sMAC (371 [167-761] versus 184 [112-249] ng/ml; P<0.001) concentrations in patients with preeclampsia. Two thirds of patients with preeclampsia had at least one nonsynonymous sequence variant in CAP genes. Conclusion: Patients with severe phenotype preeclampsia manifest functional alterations in CAP activation. Genetic variants in the CAP genes were detected in several patients, but a larger population study is necessary to fully evaluate genetic risk. Genetic screening and complement-targeted treatment may be useful in risk stratification and novel therapeutic approaches.

Acute Pancreatitis in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Pregnant women with coronavirus disease 2019 (COVID-19) infection are at risk for a variety of COVID-19 complications. CASE: We report a case of acute pancreatitis in a pregnant patient hospitalized for COVID-19 pneumonia. Comprehensive evaluation ruled out other etiologies of acute pancreatitis. Preterm labor developed at 33 5/7 weeks of gestation, and the patient delivered a liveborn male neonate; neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening was negative. The patient improved significantly postpartum and was discharged home on postpartum day 3. CONCLUSION: Coronavirus disease 2019 may present in pregnancy with a myriad of clinical symptoms other than respiratory. Acute pancreatitis represents an infrequent complication of primary COVID-19 infection.

Rare Case of Fetal Permanent Junctional Reciprocating Tachycardia Refractory to Prenatal Antiarrhythmic Therapy.

Permanent junctional reciprocating tachycardia (PJRT) is a rare form of atrioventricular reentrant tachycardia that is commonly resistant to most antiarrhythmic medication therapy and over an extended duration can result in tachycardia-induced cardiomyopathy. The prenatal presentation of PJRT is typically similar to that of other types of fetal supraventricular tachycardia (SVT), making it difficult to distinguish from other forms of SVT in utero by fetal echocardiography. Surface electrocardiography after delivery is typically required to make a definitive diagnosis of PJRT. We report a case of fetal SVT at 19 weeks' gestation refractory to maternal transplacental treatment with digoxin, amiodarone, flecainide, sotalol, metoprolol, intraumbilical amiodarone, and fetal intramuscular digoxin over the course of 12 weeks. Repeat cesarean delivery was performed at 30 2/7 weeks' gestation for tachycardia-induced cardiomyopathy with hydrops fetalis. Postnatal electrocardiogram and continuous rhythm monitoring confirmed the diagnosis of PJRT. Combined neonatal treatment with amiodarone, digoxin, and propranolol was successful in reestablishment of sinus rhythm, with radiofrequency ablation planned if medical therapy eventually fails or once early childhood is reached. To our knowledge, this is the first described case of fetal PJRT refractory to multiple standard in utero antiarrhythmic modalities and highlights the importance of inclusion in the differential diagnosis.