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Abstract BackgroundEffective cryopreservation allows for the long-term storage of living cells or tissues with the possibility of later clinical applications. Unfortunately, no successful investigations on the long-term preservation of adipose aspirates for prospective autologous fat grafting have been conducted. ObjectivesIn this study, we aimed to compare 3 different freezing methods to preserve adipose aspirates obtained from conventional lipoplasty to determine the optimal cryopreservation technique. MethodsTo determine the optimal cryopreservation technique, hematoxylin and eosin staining, MTS assay, and Annexin assay were performed on each of the 3 groups plus a fourth control group. Group 1 served as the control, and fat tissue was analyzed immediately after adipose harvesting with no cryopreservation. For experimental Group 2, 15 mL of adipose aspirates were directly frozen at −80°C for up to 2 weeks. For experimental Group 3, 15 mL of adipose aspirates were frozen inside the adi-frosty containing 100% isopropanol and stored at −80°C for up to 2 weeks. For experimental Group 4, 15 mL of adipose aspirates were frozen with freezing solution containing 90% fetal bovine serum (v/v) and 10% dimethyl sulfoxide (v/v). ResultsThe results demonstrated that the experimental Group 3 had significantly more live adipocytes and greater cellular function of adipose aspirates than the experimental Groups 2 and 4. ConclusionCryopreservation with adi-frosty containing 100% isopropanol appears to be the best means of cryopreservation of fat. Level of Evidence: 3

Abstract BackgroundWound healing is a process that involves multiple physiological steps, and despite the availability of various wound treatment methods, their effectiveness is still limited due to several factors, including cost, efficiency, patient-specific requirements, and side effects. In recent years, nanovesicles called exosomes have gained increasing attention as a potential wound care solution due to their unique cargo components which enable cell-to-cell communication and regulate various biological processes. Umbilical cord blood plasma (UCBP) exosomes have shown promise in triggering beneficial signaling pathways that aid in cell proliferation and wound healing. However, there is still very limited information about the wound-healing effect of UCBP exosomes in the literature. ObjectivesThe primary objective of this study was to investigate the “hybrosome” technology generated with calf UCBP-derived exosome–liposome combination. MethodsThe authors developed hybrosome technology by fusing cord blood exosome membranes with liposomes. Nanovesicle characterization, cell proliferation assay, wound-healing scratch assay, immunohistochemistry analysis, anti-inflammation assay, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and cellular uptake studies were performed using the novel hybrid exosomes. ResultsExperimental results showed that hybrosome increases cell proliferation and migration by 40% to 50%, depending on the dose, and induces an anti-inflammatory effect on different cell lines as well as increased wound healing–related gene expression levels in dermal cells in vitro. All in all, this research widens the scope of wound-healing therapeutics to the novel hybrosome technology. ConclusionsUCBP-based applications have the potential for wound treatments and are promising in the development of novel therapies. This study shows that hybrosomes have outstanding abilities in wound healing using in vitro approaches. Level of Evidence: 3

Ozone (O3) gas is the triatomic state of oxygen and it is used as a disinfection agent due to its strong oxidizing effect, since its discovery in the mid-nineteenth century. Ozone therapy is also an alternative therapeutic approach for some diseases like circulatory disorders, AIDS, asthma, cardiovascular diseases, and certain types of cancer by increasing the oxygen levels in the blood by external addition of ozone to the body. In this study, the therapeutic potential of ozone therapy was examined by inhibiting the growth of breast cancer cells in a dose-dependent procedure. Ozone concentrations varying from 5 to 20 ​μg/ml were applied to the MDA-MB-231, human breast adenocarcinoma and HUVEC, human umbilical vein endothelium, cell lines, and MDA cells demonstrated an increased rate of death while its migration potential decreases. RT-PCR analysis showed mRNA expression levels of pro-apoptotic genes demonstrated higher folds in MDA cells after 10 ​μg/ml treatment. In the same context, Annexin V/PI and cell cycle analysis also concluded that ozone therapy causes apoptotic cell death on breast tumor cells. The use of ozone therapy for cancer treatment requires further and extensive research. However, this research has shown that ozone therapy is a promising source for cancer treatment in a way by inhibiting the proliferation of breast tumor cells.

Background:. Enzymatic digestion of extracellular matrix (ECM) from lipoaspirate is the conventional form of harvesting stromal vascular fraction (SVF) called enzymatically digested SVF (E-SVF). Mechanical SVF (M-SVF) isolation has emerged as an alternative method, but it has also some limitations in terms of lower cell viability and diminished cell counts. To enhance the SVF qualitatively and quantitatively, we propose a novel concept called "hybrid-SVF,” in which we combine M-SVF with the concentrated parts of adipose tissue after centrifugation, which is called stromal vascular matrix (SVM). Methods:. Hybrid-SVF injection was applied as an adjunctive therapy to fat grafting in 88 patients and 11 samples were evaluated in the laboratory for cell count, viability and cell activity. Results:. Experimental results determined that SVM part showed higher cellular activity. SVM and M-SVF showed higher cellular potency than E-SVF. Clinically, none of the patients required an additional session for fat grafting since there was no significant graft resorption. However, seven patients asked for further volume augmentation due to their individual preferences. No major complication was encountered. Conclusions:. The usage of hybrid-SVF has a very high regenerative potential due to the ECM support and exceptionally high cell yield in addition to preserved cell potency. Although there are ongoing studies focusing on optimizing cell counts and further clinical applications, we believe that our preliminary results might create a paradigm shift in the area of regenerative fat grafting.

Abstract As a key component of the cell-to-cell communication, small extracellular vesicles (SEVs) released from various sources are known to be affecting the physiological conditions of the target cells. Although it has been suggested that edible plant-derived nanoparticles contributes to the cross kingdom communication with the mammalian cells, the effect of these particles on cancer cell progression still needs a further exploration. Here, we isolated and then characterized garlic derived SEVs by nanoparticle tracking analysis, electron microscopy and SEV surface antibodies. In order to investigate anti-cancer property of garlic SEVs A498 human kidney carcinoma, A549 human lung carcinoma were used as cell models along with the normal human dermal fibroblast cell lines. Annexin V/pI staining and analysis of apoptotic mRNA and protein expression levels suggested that garlic SEVs induced apoptosis through activation of intrinsic pathway. Furthermore, angiogenic VEGF protein expression levels significantly decreased in response to SEVs treatment in cancer cells. Our results support that garlic derived SEVs could cause apoptotic cell death among cancer cells while normal cells remain unaffected with the treatment. This study revealed for the first time that plant SEVs possess anti-cancer affects by inducing caspase mediated apoptosis and provided a new alternative for cancer treatment.

Smart engineered and naturally derived nanovesicles, capable of targeting specific tissues and cells and delivering bioactive molecules and drugs into them, are becoming important drug delivery systems. Liposomes stand out among different types of self-assembled nanovesicles, because of their amphiphilicity and non-toxic nature. By modifying their surfaces, liposomes can become stimulus-responsive, releasing their cargo on demand. Recently, the recognized role of exosomes in cell-cell communication and their ability to diffuse through tissues to find target cells have led to an increase in their usage as smart delivery systems. Moreover, engineering “smarter” delivery systems can be done by creating hybrid exosome-liposome nanocarriers via membrane fusion. These systems can be loaded in naturally derived hydrogels to achieve sustained and controlled drug delivery. Here, the focus is on evaluating the smart behavior of liposomes and exosomes, the fabrication of hybrid exosome-liposome nanovesicles, and the controlled delivery and routes of administration of a hydrogel matrix for drug delivery systems.

Background: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress., Methods: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture., Results: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture., Conclusions: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage., Competing Interests: Disclosures None.

As the worldwide COVID-19 pandemic unfolded, the clinical and public health community raced to understand SARS-CoV-2 infection and develop life-saving vaccines. Pregnant persons were disproportionately impacted, experiencing more severe illness and adverse pregnancy outcomes. And yet, when COVID-19 vaccines became available in late 2020, safety and efficacy data were not available to inform their use during pregnancy because pregnant persons were excluded from pre-authorization clinical trials. Concerns about vaccine safety during pregnancy and misinformation linking vaccination and infertility circulated widely, creating a lack of vaccine confidence. Many pregnant people initially chose not to get vaccinated, and while vaccination rates rose after safety and effectiveness data became available, COVID-19 vaccine acceptance was suboptimal and varied across racial and ethnic distribution of the pregnant population. The COVID-19 pandemic experience provided valuable insights that can inform current and future approaches to maternal vaccination against., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Pregnant and postpartum women are at increased risk for severe illness from COVID-19 compared with nonpregnant women of reproductive age. COVID-19 vaccination is recommended for all persons ≥6 months of age. Health care providers (HCPs) have a unique opportunity to counsel women of reproductive age, including pregnant and postpartum patients, about the importance of receiving COVID-19, influenza, and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Data from the Fall 2022 DocStyles survey were analyzed to examine the prevalence of COVID-19 vaccination attitudes and practices among HCPs caring for women of reproductive age, and to determine whether providers recommended and offered or administered COVID-19 vaccines to women of reproductive age, including their pregnant patients. Overall, 82.9% of providers reported recommending COVID-19 vaccination to women of reproductive age, and 54.7% offered or administered the vaccine in their practice. Among HCPs who cared for pregnant patients, obstetrician-gynecologists were more likely to recommend COVID-19 vaccination to pregnant patients (94.2%) than were family practitioners or internists (82.1%) (adjusted prevalence ratio [aPR] = 1.1). HCPs were more likely to offer or administer COVID-19 vaccination on-site to pregnant patients if they also offered or administered influenza (aPR = 5.5) and Tdap vaccines (aPR = 2.3). Encouraging HCPs to recommend, offer, and administer the COVID-19 vaccines along with influenza or Tdap vaccines might help reinforce vaccine confidence and increase coverage among women of reproductive age, including pregnant women., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Zika virus (ZIKV) infection during pregnancy can cause severe birth defects in the fetus and is associated with neurodevelopmental abnormalities in childhood. Our objective was to describe ZIKV knowledge and attitudes among pregnant women in Colombia while ZIKV was circulating and whether they predicted the adoption of behaviors to prevent ZIKV mosquito-borne and sexual transmission., Methods: We used self-reported data from Zika en Embarazadas y Niños (ZEN), a cohort study of women in early pregnancy across three regions of Colombia during 2017-2018. We used Poisson regression to estimate associations between knowledge, attitudes and previous experience with mosquito-borne infection and preventative behaviors., Results: Among 1519 women, knowledge of mosquito-borne transmission was high (1480; 97.8%) and 1275 (85.5%) participants were worried about ZIKV infection during pregnancy. The most common preventive behavior was wearing long pants (1355; 89.4%). Regular mosquito repellent use was uncommon (257; 17.0%). While ZIKV knowledge and attitudes were not associated with the adoption of ZIKV prevention behaviors, previous mosquito-borne infection was associated with increased condom use (prevalence ratio 1.4, 95% CI 1.1 to 1.7)., Conclusions: Participants were well informed about ZIKV transmission and its health consequences. However, whether this knowledge resulted in behavior change is less certain., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Pregnant people with COVID-19 are at increased risk for severe illness and adverse pregnancy outcomes. COVID-19 vaccinations are safe and effective, including for pregnant and recently pregnant people. The objective of this analysis was to describe the extent to which primary care physicians across the United States report confidence in talking with female patients of reproductive age about COVID-19 vaccination, recommending COVID-19 vaccinations to pregnant patients, and offering COVID-19 vaccinations at their practices in fall 2021. We analyzed cross-sectional data from the Fall 2021 DocStyles survey, a web-based panel survey of U.S. primary healthcare providers (64% response rate). Family practitioners/internists, obstetrician-gynecologists, and pediatricians were asked about confidence in talking with female patients of reproductive age about COVID-19 vaccination, vaccination practices regarding pregnant patients, and offering COVID-19 vaccinations. We describe results overall and by select physician characteristics. Among 1501 respondents, most were family practitioners/internists (67%), 17% were obstetrician-gynecologists, and 17% were pediatricians. Overall, 63% were very confident talking with female patients of reproductive age about COVID-19 vaccination, 80% recommended pregnant patients get vaccinated as soon as possible, and 50% offered COVID-19 vaccinations at their current practice. Obstetrician-gynecologists were most confident in talking with female patients, but only one-third offered the vaccine at their practices. This analysis found that most physicians felt confident talking about COVID-19 vaccinations and recommended pregnant patients get vaccinated as soon as possible. Provider recommendation for vaccination remains a key strategy for achieving high vaccination coverage, and consistent recommendations may improve vaccine acceptance among pregnant and postpartum people., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Pregnant and postpartum women are at increased risk for severe illness from COVID-19. We assessed COVID-19 vaccination coverage, intent, and attitudes among women of reproductive age overall and by pregnancy status in the United States., Methods: Data from the National Immunization Survey Adult COVID Module collected during April 22-November 27, 2021, were analyzed to assess COVID-19 vaccination (receipt of ≥1 dose), intent for vaccination, and attitudes towards vaccination among women aged 18-49 years overall and by pregnancy status (trying to get pregnant, currently pregnant, breastfeeding, and not trying to get pregnant or currently pregnant or breastfeeding). Logistic regression and predictive marginals were used to generate unadjusted and adjusted prevalence ratios (PRs and aPRs). Trend analyses were conducted to assess monthly changes in vaccination and intent., Results: Our analyses included 110,925 women aged 18-49 years. COVID-19 vaccination coverage (≥1 dose) was 63.2% overall (range from 53.3% in HHS Region 4 to 76.5% in HHS Region 1). Vaccination coverage was lowest among pregnant women (45.1%), followed by women who were trying to get pregnant (49.5%), women who were breastfeeding (51.5%), and all other women (64.9%). Non-Hispanic (NH) Black women who were pregnant or breastfeeding had significantly lower vaccination coverage (aPR: 0.74 and 0.66, respectively) than NH White women., Discussion: Our findings are consistent with other studies showing lower vaccination coverage among pregnant individuals, with substantially lower vaccination coverage among NH Black women who are pregnant or breastfeeding. Given the overlapping and disproportionate risks of COVID-19 and maternal mortality among Black women, it is critical that COVID-19 vaccination be strongly recommended for these populations and all women of reproductive age. Healthcare and public health providers may take advantage of every opportunity to encourage vaccination and enlist the assistance of community leaders, particularly in communities with low vaccination coverage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Amanda Elmore reports support from the Florida Birth Defects Registry, Surveillance, Intervention, and Referral to Services for Infants with Microcephaly or Other Adverse Outcomes linked with the Zika Virus in Florida. Jane Fornoff reports that she is vice-chair of the Illinois Department of Public Health’s Institutional Review Board. Nicole D. Longcore reports grant support from Epidemiology and Laboratory Capacity for Infectious Diseases. Amy E. Nance reports that the is co-chair for Communication and Health Promotion of the National Birth Defect Prevention Network. Brennan Martin reports being a member-at-large for the National Birth Defect Prevention Network (2019). No other potential conflicts of interest were disclosed.

Objectives: To understand the information needs and experiences with health care and social support among women with confirmed or possible Zika virus infection during pregnancy., Methods: We conducted in-depth interviews with 18 women whose pregnancies were part of surveillance efforts in two states, Pennsylvania and Virginia. Using a semi-structured guide available in English and Spanish, we asked women about their experiences. We conducted a thematic analysis using NVivo 11., Results: Only one participant reported that her infant had been diagnosed with health problems related to congenital Zika virus infection. Most participants said they received the information they needed about Zika virus and their infant's medical care. Most participants primarily spoke Spanish and described satisfactory experiences communicating with providers, either using a mix of Spanish and English or using an interpreter. Coordination of care and clear communication among different providers was a key factor in participants' satisfaction with health care received. Participants noted high levels of stress around the uncertainty associated with Zika virus exposure during pregnancy., Conclusions for Practice: Although participants reported satisfaction with care, they also reported high levels of anxiety and challenges coping with the uncertainties along their journeys. Study findings support the need for guidance for providers about how to talk with women about Zika virus infection during pregnancy and specifically how to discuss the uncertainties about diagnosis and outcomes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pregnant women are at increased risk for severe COVID-19-related illness, and COVID-19 is associated with an increased risk for adverse pregnancy outcomes and maternal and neonatal complications (1-3). To date, studies assessing whether COVID-19 during pregnancy is associated with increased risk for stillbirth have yielded mixed results (2-4). Since the B.1.617.2 (Delta) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant,* there have been anecdotal reports of increasing rates of stillbirths in women with COVID-19. † CDC used the Premier Healthcare Database Special COVID-19 Release (PHD-SR), a large hospital-based administrative database, § to assess whether a maternal COVID-19 diagnosis documented at delivery hospitalization was associated with stillbirth during March 2020-September 2021 as well as before and during the period of Delta variant predominance in the United States (March 2020-June 2021 and July-September 2021, respectively). Among 1,249,634 deliveries during March 2020-September 2021, stillbirths were rare (8,154; 0.65%): 273 (1.26%) occurred among 21,653 deliveries to women with COVID-19 documented at the delivery hospitalization, and 7,881 (0.64%) occurred among 1,227,981 deliveries without COVID-19. The adjusted risk for stillbirth was higher in deliveries with COVID-19 compared with deliveries without COVID-19 during March 2020-September 2021 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.69-2.15), including during the pre-Delta (aRR = 1.47; 95% CI = 1.27-1.71) and Delta periods (aRR = 4.04; 95% CI = 3.28-4.97). COVID-19 documented at delivery was associated with increased risk for stillbirth, with a stronger association during the period of Delta variant predominance. Implementing evidence-based COVID-19 prevention strategies, including vaccination before or during pregnancy, is critical to reducing the impact of COVID-19 on stillbirths., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territories † with local transmission of Zika virus reported 2,549 completed pregnancies § (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection ¶ (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).

The marked increase in infants born with microcephaly in Brazil after a 2015 outbreak of Zika virus (Zika virus) disease suggests an association between maternal Zika virus infection and congenital microcephaly. To project the timing of delivery of infants born to mothers infected during early pregnancy in 1 city in Bahia State, Brazil, we incorporated data on reported Zika virus disease cases and microcephaly cases into a graphical schematic of weekly birth cohorts. We projected that these births would occur through February 2016. Applying similar projections to a hypothetical location at which Zika virus transmission started in November, we projected that full-term infants at risk for Zika virus infection would be born during April-September 2016. We also developed a modifiable spreadsheet tool that public health officials and researchers can use for their countries to plan for deliveries of infants to women who were infected with Zika virus during different pregnancy trimesters.