Menstrual management using the etonogestrel implant in individuals with intellectual disabilities in Joinville, Brazil.

OBJECTIVE: This study aimed to describe the use of etonogestrel (ENG) implants for menstrual management (i.e., management of bleeding and symptoms associated with menstruation) in individuals with intellectual disabilities. METHODS: This study retrospectively analyzed a cohort of individuals with intellectual disabilities who began using ENG implants between 2003 and 2018, in Joinville, Brazil. We collected sociodemographic, clinical, and reproductive data from the medical records, along with information related to ENG implant use. RESULTS: In total, 369 implants were placed in 130 individuals with intellectual disabilities. The median age at the first implant was 20 (interquartile range [IQR], 17-26) years, and 43.8% of the patients were adolescents. By December 2018, 90 patients had received two or more subsequent implants. The median duration of current ENG implant use was 19 (IQR, 12.8-22) months. More than 40% of the patients had comorbidities, with epilepsy being the most common. During the use of the current implant, 80% of the patients had a favorable bleeding profile (no bleeding or ≤1 bleeding episode per month), and 53.8% (70/130) had no bleeding within 3 months before their last medical visit. Among patients experiencing dysmenorrhea and premenstrual syndrome (PMS), 79% (64/81) and 82% (54/66) reported complete improvement, respectively. The premature implant removal rate was 8.9% (33/369). Unfavorable bleeding was the main reason for premature implant removal (20 out 33 removals). CONCLUSIONS: ENG implants might be a suitable option for individuals with intellectual disabilities who require management of menstrual bleeding and symptoms associated with menstruation. Most patients had a favorable bleeding profile and experienced significant improvements in dysmenorrhea and PMS, contributing to the high continuation rates of ENG implants.

Women's experiences with the post-placental intrauterine device: a qualitative study.

Objective: To explore women's experiences with postpartum intrauterine device (PPIUD) insertion and the decision-making process in the postpartum period. Methods: A qualitative design was employed with face-to-face interviews using a semi-structured script of open questions. The sample was intentionally selected using the concept of theoretical information saturation. Results: Interviews were conducted (1) in the immediate postpartum period, and (2) in the postpartum appointment. 25 women (N = 25) over 18 years old who had a birth followed by PPIUD insertion were interviewed between October 2021 and June 2022. Three categories were constructed: (1) Choice process, (2) Relationship with the health team at the time of birth and the postpartum period, and (3) To know or not to know about contraception, that is the question. Conclusion: Professionals' communication management, popular knowledge, advantages of the PPIUD and the moment PPIUD is offered play a fundamental role in the construction of knowledge about the IUD. Choice process did not end in the insertion.

Immediate vs delayed postpartum insertion of long-acting reversible contraception methods: meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to conduct a meta-analysis of randomized trials comparing the immediate vs delayed provision of long-acting reversible contraceptives in postpartum subjects, focusing on short-interval pregnancies, utilization rates, and adverse events. DATA SOURCES: Cochrane Central, Embase, PubMed, and ClinicalTrials.gov were systematically searched from inception up to December 19, 2023, without filters or language limitation. STUDY ELIGIBILITY CRITERIA: We selected randomized controlled trials assessing the immediate insertion of long-acting reversible contraceptives in women during postpartum period in comparison with the delayed provision. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated relative risks with 95% confidence intervals to analyze the primary outcome of utilization rates and secondary endpoints, including initiation rates, pregnancy, any breastfeeding, exclusive breastfeeding, and serious adverse events. A random-effects model was employed in the R software. Moreover, we assessed the risk of bias of selected randomized controlled trials using version 2 of the Cochrane Risk of Bias Assessment Tool. RESULTS: We included 24 randomized trials comprising 2507 participants, of whom 1293 (51.6%) were randomized to the immediate insertion. Postpartum women in the immediate group had lower risk of pregnancy (relative risk 0.16; 95% confidence interval 0.04-0.71; P=.02) compared with delayed group, and higher rates of long-acting reversible contraceptives at 6 months of follow-up (relative risk 1.23; 95% confidence interval 1.09-1.37; P<.01). CONCLUSION: Inserting long-acting reversible contraceptives before hospital discharge was associated with a reduction in the risk of pregnancy, and increased rates of its utilization at 6 months of follow-up. This intervention may be an effective contraception strategy for postpartum women.

Posterior Reversible Encephalopathy Syndrome Associated with L-Asparaginase Treatment in Children: Literature Review and Six Case Reports.

L-asparaginase (L-ASNase) is an enzyme that shows targeted activity against Acute Lymphoblastic Leukemia (ALL) and similar lymphoid neoplasms by facilitating the breakdown of asparagine into L-aspartic acid, thereby reducing L-asparagine levels in leukemic cells. However, its therapeutic potential is hindered by its associated toxicity, leading to complications, such as thrombosis, hemorrhage, thrombocytopenia, fibrinolysis, hypersensitivity reactions, and the development of Posterior Reversible Encephalopathy Syndrome (PRES). This review compiles documented cases of PRES linked to treating B and T cell acute lymphoblastic leukemia in children using L-ASNase. Although this pathology is rare, understanding its management is crucial within ASNase-based chemotherapy protocols. As PRES lacks a specific treatment, focusing on symptomatic management becomes pivotal. Therefore, comprehending the underlying causes during L-ASNase treatment for acute lymphoblastic leukemia is essential. Understanding the etiology and clinical symptoms of this illness is critical for early diagnosis and treatment. The cases of PRES described in this review include instances in which this syndrome has appeared after the administration of L-ASNase in children. In some cases, PRES developed during induction therapy, while in others, it occurred during the reinduction phase. These cases resolved days after discontinuation of L-ASNase. The findings suggest a close relationship between drug administration and the appearance of brain lesions, as evidenced by the disappearance or decrease of these lesions when the drug was eliminated from the bloodstream.

The Structural Stability of Membrane Proteins Revisited: Combined Thermodynamic and Spectral Phasor Analysis of SDS-induced Denaturation of a Thermophilic Cu(I)-transport ATPase.

Assessing membrane protein stability is among the major challenges in protein science due to their inherent complexity, which complicates the application of conventional biophysical tools. In this work, sodium dodecyl sulfate-induced denaturation of AfCopA, a Cu(I)-transport ATPase from Archaeoglobus fulgidus, was explored using a combined model-free spectral phasor analysis and a model-dependent thermodynamic analysis. Decrease in tryptophan and 1-anilino-naphthalene-8-sulfonate fluorescence intensity, displacements in the spectral phasor space, and the loss of ATPase activity were reversibly induced by this detergent. Refolding from the SDS-induced denatured state yields an active enzyme that is functionally and spectroscopically indistinguishable from the native state of the protein. Phasor analysis of Trp spectra allowed us to identify two intermediate states in the SDS-induced denaturation of AfCopA, a result further supported by principal component analysis. In contrast, traditional thermodynamic analysis detected only one intermediate state, and including the second one led to overparameterization. Additionally, ANS fluorescence spectral analysis detected one more intermediate and a gradual change at the level of the hydrophobic transmembrane surface of the protein. Based on this evidence, a model for acquiring the native structure of AfCopA in a membrane-like environment is proposed.

Improved Operation of Chloralkaline Reversible Cells with Mixed Metal Oxide Electrodes Made Using Microwaves.

This study focuses on the synthesis of mixed metal oxide anodes (MMOs) with the composition Ti/RuO2Sb2O4Ptx (where x = 0, 5, 10 mol) using hybrid microwave irradiation heating. The synthesized electrodes were characterized using scanning electron microscopy, X-ray energy-dispersive analysis, X-ray diffraction, cyclic voltammetry, and electrochemical impedance spectroscopy. These electrodes were then evaluated in both bulk electrolytic and fuel cell tests within a reversible chloralkaline electrochemical cell. The configurations using the electrodes Ti/(RuO2)0.7-(Sb2O4)0.3 and Ti/(RuO2)66.5-(Sb2O4)28.5-Pt5 presented lower onset potential for oxygen and chlorine evolution reactions and reduced resistance to charge transfer compared to the Ti/(RuO2)63-(Sb2O4)27-Pt10 variant. These electrodes demonstrated notable performance in reversible electrochemical cells, achieving Coulombic efficiencies of up to 60% when operating in the electrolytic mode at current densities of 150 mA cm-2. They also reached maximum power densities of 1.2 mW cm-2 in the fuel cell. In both scenarios, the presence of platinum in the MMO coating positively influenced the process. Furthermore, a significant challenge encountered was crossover through the membranes, primarily associated with gaseous Cl2. This study advances our understanding of reversible electrochemical cells and presents possibilities for further exploration and refinement. It demonstrated that the synergy of innovative electrode synthesis strategies and electrochemical engineering can lead to promising and sustainable technologies for energy conversion.

Long-acting reversible contraception use and unmet desire among patients after the Zika Contraception Access Network Program in Puerto Rico.

OBJECTIVES: To describe unmet desire for long-acting reversible contraception (LARC) after the Zika Contraception Access Network (Z-CAN) in Puerto Rico during the 2016-2017 Zika outbreak. STUDY DESIGN: Z-CAN patients completed surveys about contraception experiences over a 3-year period. RESULTS: Of 1809 respondents, 3% never used LARC but reported wanting it since their initial visit. As reasons for not getting LARC, nearly 50% indicated a provider-related reason and 25% reported cost. CONCLUSIONS: Few Z-CAN patients who never used LARC had unmet desire. Provider training in contraception guidelines and strategies to address costs can expand access to the full range of reversible contraception. IMPLICATIONS: Three years after a short-term program provided reversible contraception in Puerto Rico, few respondents had never used but wanted a long-acting reversible contraception method. Nearly half reported provider-related reasons for not receiving long-acting reversible contraception, and 25% reported cost. Provider awareness of contraceptive guidance and method availability can support client-centered care.

Barriers to accessing post-pregnancy contraception in Brazil: The impact of COVID-19.

The aim of our article is to discuss barriers associated with post-pregnancy contraception in Brazil during the SARS-CoV-2 (COVID-19) pandemic. Socioeconomic differences in gaining access to long-acting reversible contraceptive (LARC) methods became greater during the COVID-19 pandemic. The inadequate distribution of existing resources and the reduced capacity for elective care meant that healthcare providers in family planning had to be reallocated to respond to COVID-19 emergencies. In Brazil, 74% of the population depends on the national health service (Sistema Unico de Saúde) including for the provision of free contraception. However, the only LARC method available at the public service is the copper-intrauterine device (IUD); implants and hormonal-IUDs are not available, except at some teaching hospitals. Contraceptive sales remained unmodified during the pandemic, which shows that the majority of the population used less effective or no contraceptive methods during this time. However, sales of implants and the hormonal-IUD increased significantly, indicating the inequity of the low-income portion of the society as only the wealthy can afford these. On the other hand, there was an increase in sales of emergency contraception. The uptake of postpartum IUDs and contraceptive implants at the selected teaching hospitals in which they were available was high during the COVID-19 pandemic as they were the only methods immediately available. In conclusion, the COVID-19 pandemic increased both inequality and social differences in gaining access to contraceptives. Postpartum and immediate post abortion methods were also good strategies during the pandemic and were well accepted by the population. However, they were not offered by most services.

Uptake, discontinuation, and continuation rate of long-acting contraceptive methods when offered at no cost in Campinas, Brazil.

OBJECTIVES: This study aimed to compare the uptake, reasons for discontinuation, continuation, and satisfaction of long-acting contraceptive methods (LARC) when offered at no cost in Campinas, Brazil. STUDY DESIGN: This was a prospective cohort study conducted at University of Campinas, Campinas, São Paulo, Brazil, including women aged 18 to 48 years, who adopted one of three methods. Participants underwent telephone follow-up every 3 months for up to 24 months after insertion. Satisfaction was assessed at the end of 2 years of use through the Likert scale. RESULTS: We invited 1222 women, and among the 971 women who volunteered to participate in follow-up, 414 (42.6%) chose the levonorgestrel 52-mg intrauterine device (IUD), 358 (36.9%) chose the etonogestrel (ENG) implant, and 199 (20.5%) chose the TCu380A IUD. Discontinuation due to bothersome bleeding was higher among users of the ENG implant (10/358; 2.4%) and the TCu380A IUD (32/199; 8.9%), and expulsion was higher for the TCu380A IUD (30/199; 15.1%). Women continued at 24 months were 340/414 (82.1%), 270/358 (75.4%), and 119/199 (59.8%) among users of the levonorgestrel 52-mg IUD, ENG implant, and TCu380A IUD, respectively. The users of the levonorgestrel 52-mg IUD (301/339, 88.8%), the ENG-implant (222/270, 82.2%), and the TCu380A IUD (105/119, 88.2%) were satisfied or very satisfied by 24 months of follow-up. CONCLUSIONS: The three LARC methods had great uptake, high continuation, and discontinuation due to bothersome bleeding was higher among users of the ENG implant and the TCu380A IUD, and expulsion was higher for the TCu380A IUD compared to the 52-mg levonorgestrel IUD. Most of the participants reported being very satisfied. IMPLICATIONS: When the LARC methods were offered at no cost in a Brazilian public clinic the uptake, satisfaction and continuation were high by 24 months after device placement, and high level of satisfaction was reported by most of the participants.

Evidence of intrauterine device insertion by nurses in Primary Health Care: an integrative review / Evidencias de inserción de dispositivos intrauterinos por parte de enfermeros en Atención Primaria de Salud: revisión integradora / Evidências da inserção de dispositivo intrauterino por enfermeiros na Atenção Primária à Saúde: revisão integrativa

ABSTRACT Objectives: to synthesize and analyze evidence on intrauterine device insertion by nurses in Primary Health Care. Methods: an integrative review, carried out in the BDENF, CINAHL, LILACS, SciELO, Scopus, PubMed and Web of Science databases in June 2022, delimiting the period from 1960 to 2022. Results: 141 articles were identified in the initial search, and 10 studies made up the final sample. Four (40%) were developed in the United States and one (10%) in Brazil, with publications from 1979 to 2021. The findings were grouped into three categories: Nurse training to insert an intrauterine device; Nurses' competency to insert an intrauterine device; and Women's access to intrauterine devices. Conclusions: nurse theoretical and practical training is a prominent element, consolidated in the favorable outcomes of insertions performed by nurses and satisfaction among women, a practice that has expanded access to the contraceptive method in Primary Health Care.

RESUMEN Objetivos: sintetizar y analizar la evidencia sobre la inserción de dispositivos intrauterinos por parte de enfermeras en la Atención Primaria de Salud. Métodos: revisión integrativa, realizada en las bases de datos BDENF, CINAHL, LILACS, SciELO, Scopus, PubMed y Web of Science en junio de 2022, delimitando el período de 1960 a 2022. Resultados: se identificaron 141 artículos en la búsqueda inicial y 10 publicaciones conformaron la muestra final. Cuatro (40%) fueron desarrollados en Estados Unidos y uno (10%) en Brasil, con publicaciones de 1979 a 2021. Los hallazgos se agruparon en tres categorías: Capacitación de enfermeras para insertar un dispositivo intrauterino; Competencia de las enfermeras para insertar un dispositivo intrauterino; y Acceso de las mujeres a los dispositivos intrauterinos. Conclusiones: la formación teórica y práctica de los enfermeros es un elemento destacado, consolidado en los resultados favorables de las inserciones realizadas por los enfermeros y la satisfacción de las mujeres, práctica que ha ampliado el acceso al método anticonceptivo en la Atención Primaria de Salud.

RESUMO Objetivos: sintetizar e analisar as evidências da inserção de dispositivo intrauterino por enfermeiros na Atenção Primária à Saúde. Métodos: revisão integrativa, realizada nas bases de dados BDENF, CINAHL, LILACS, SciELO, Scopus, PubMed e Web of Science em junho de 2022, delimitando-se o período de 1960 a 2022. Resultados: identificaram-se 141 artigos na busca inicial, e 10 publicações compuseram a amostra final. Quatro (40%) foram desenvolvidos nos Estados Unidos e um (10%) no Brasil, sendo publicações de 1979 a 2021. Os achados foram agrupados em três categorias: Treinamento dos enfermeiros para inserção de dispositivo intrauterino; Competência dos enfermeiros para inserção de dispositivo intrauterino; e Acesso das mulheres aos dispositivos intrauterinos. Conclusões: o treinamento teórico e prático dos enfermeiros é um elemento de destaque, consolidado nos desfechos favoráveis das inserções realizadas por enfermeiros e satisfação entre as mulheres, prática que tem ampliado o acesso ao método contraceptivo na Atenção Primária à Saúde.

Women's experiences with the post-placental intrauterine device: a qualitative study

Abstract Objective: To explore women's experiences with postpartum intrauterine device (PPIUD) insertion and the decision-making process in the postpartum period. Methods: A qualitative design was employed with face-to-face interviews using a semi-structured script of open questions. The sample was intentionally selected using the concept of theoretical information saturation. Results: Interviews were conducted (1) in the immediate postpartum period, and (2) in the postpartum appointment. 25 women (N = 25) over 18 years old who had a birth followed by PPIUD insertion were interviewed between October 2021 and June 2022. Three categories were constructed: (1) Choice process, (2) Relationship with the health team at the time of birth and the postpartum period, and (3) To know or not to know about contraception, that is the question. Conclusion: Professionals' communication management, popular knowledge, advantages of the PPIUD and the moment PPIUD is offered play a fundamental role in the construction of knowledge about the IUD. Choice process did not end in the insertion.

Use of long-acting contraceptive methods and main concerns among women in Brazil / Uso de métodos contraceptivos de longa ação e principais preocupações de suas usuárias

Abstract Objectives: to assess factors associated with the use of long-acting reversible methods (LARC) and women's concerns about them. Methods: this is a cross-sectional study conducted in a digital environment from April to June 2021, with the use of a structured instrument disseminated through social networks. The study included women of reproductive age (18 to 49 years old), who were not pregnant, not hysterectomized, not sterilized and whose partners were not vasectomized. Data were analyzed using logistic and multinomial regression. Results: the study population consisted of 1596 women aged 18 to 49 living in all regions of the country, 22% of whom were using LARC. Aspects associated with LARC use were younger age, having health insurance, being in a relationship and not wanting to get pregnant. Half of LARC users reported having some kind of concern about the method, the most frequent being the risk of becoming pregnant (36.2%). The aspects associated with having concerns about using LARC were the type of method, not being in a relationship and not wanting to get pregnant. Conclusions: LARC users are not a homogeneous group. Current experience of using LARC is lived with concerns, including some about its efficacy.

Resumo Objetivos: determinar os fatores associados ao uso de métodos reversíveis de longa ação (LARC) e às preocupações das usuárias. Métodos: estudo transversal conduzido em ambiente digital de abril a junho de 2021, por meio de instrumento estruturado disseminado por redes sociais. Foram incluídas mulheres em idade reprodutiva (18 a 49 anos de idade), não grávidas, não histerectomizadas, não esterilizadas e cujos parceiros não eram vasectomizados. Os dados foram analisados por meio de regressão logística e multinominal. Resultados: a população do estudo foi constituída por 1596 mulheres de 18 a 49 anos de idade residentes em todas as regiões do país, das quais 22% usavam LARC. Os aspectos associados ao uso de LARC foram a idade mais jovem, ter plano de saúde, estar em um relacionamento e não querer engravidar. Metade das usuárias de LARC relatou ter algum tipo de preocupação com o método, sendo a mais frequente o risco de engravidar (36,2%). Os aspectos associados a ter preocupação com o uso de LARC foram o tipo de método, não estar em um relacionamento e não querer engravidar. Conclusões: observou-se que as usuárias de LARC não são homogêneas entre si e que a experiência com o uso de LARC está permeada por preocupações, inclusive em relação a sua eficácia.

Protocol to Induce the Temporary Opening of the Blood-Brain Barrier with Short-Time Focused Ultrasound in Rats.

Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood-Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching the brain. There are indications that Focused Ultrasound (FUS), temporarily placed in the BBB, can achieve a controlled increase in temperature at its focus, allowing temporary, localized, and reversible opening of this barrier, which facilitates the temporary delivery of specific drugs. This work presents a FUS-based protocol for the local, temporary, and reversible opening of the BBB in Wistar rats. The proposed protocol specifies certain power, treatment times, and duty cycle to controllably increase the temperature at the region of interest, i.e., the substantia nigra. Numerical simulations using commercial software based on the finite element method were carried out to determine the optimal size of the craniotomies for nearly full-acoustic transmission. Experiments in rats were performed with the parameters used during computational simulations to determine the adequate opening of the BBB. For this, craniotomies of different sizes were made at coordinates of the substantia nigra, and FUS was applied from the exterior. The opening of the BBB was evaluated using Evans Blue (EB) as an indicator of the crossing of the dye from the blood vessels to brain tissue. Numerical simulations demonstrated a major distance reached by the ultrasound focus with a bigger diameter. Experimental results show the local, temporary, and reversible opening of the BBB through a 10 mm diameter craniotomy, which effectively allowed placing the ultrasound focus over the substantia nigra, unlike a 6 mm diameter craniotomy in which there is a deviation of the focus through that window. Moreover, from these results, it was also determined that the disruption of the BBB was reversible, with an opening duration of 6 h after FUS application. The experimental work developed in this study resulted in a minimally invasive method for the temporary opening of the BBB.

Knowledge, attitudes, and perceptions of health care providers regarding the recommendation and use of long-acting reversible contraceptive devices for adolescent patients.

OBJECTIVE: To describe the knowledge, attitudes, and perceptions of healthcare providers in a region in southwestern Colombia regarding the recommendation and use of long-acting reversible contraceptive (LARC) methods for adolescents. STUDY DESIGN: This was a cross-sectional study. An online exploratory survey was designed to assess healthcare providers' knowledge, attitudes, and perceptions of Valle del Cauca hospitals. For the development of this the questionnaire, a literature search and validation of the instrument's appearance were conducted. RESULTS: The survey was completed by 115 people. Knowledge: 62.6% and 33% of the participants did not consider themselves capable of correctly placing an intrauterine device (IUD) or a subdermal implant, respectively. However, 73.9% of the participants had adequate theoretical knowledge. Attitudes: 64.3% of the participants considered that adolescents can acquire contraceptive methods without limitations. Short-acting reversible methods were the least recommended. Perceptions: For IUDs, 40.8% and 16.5% of the participants imposed a minimum age and minimum parity requirement for their use, respectively. Side effects were the main reason for not recommending in health institutions with a lower level of complexity. CONCLUSION: Healthcare providers had positive attitudes and adequate theoretical knowledge concerning to the effectiveness of LARCs. The main areas for improvement were practical knowledge about the insertion and proper use of the devices, indications for referral to gynaecologists for the insertion procedure, and concerns about side effects.

Our research explores healthcare providers' knowledge, attitudes, and perceptions regarding long-acting reversible contraceptives for adolescents. While attitudes were positive, practical knowledge gaps on device, placement and referral indications emerged. Read the full findings to uncover more about LARCs in adolescent healthcare.

Epidemiological profile and effectiveness of immediate postpartum contraception in Brazilian women.

Purpose: To determine the epidemiological profile of women who inserted copper intrauterine device (Cu-IUD), subdermal etonogestrel implant (ENG), tubal ligation (TL), depot medroxyprogesterone acetate (DMPA) or did not choose a contraceptive method (NCM) in the immediate postpartum period and compare the contraceptive effectiveness of Cu-IUD and DPMA with non-MAC. Methods: We analyzed the epidemiological profile of women who inserted copper intrauterine device (Cu-IUD), subdermal etonogestrel implant (ENG), tubal ligation (TL), depot medroxyprogesterone acetate (DMPA) or did not choose a contraceptive method (NCM) in the immediate postpartum. The data was collected by electronic medical records of postpartum women assisted at the University Hospital of São Bernardo do Campo (HMU-SBC) from January 2016 to December 2020. Also, we compared the contraceptive effectiveness of Cu-IUD and DPMA with non-MAC by identifying women who returned for second delivery during the study period and analyzing the contraceptive method chosen in the first hospitalization. Then the pregnancies interval and the sociodemographic characteristics were analyzed according to contraceptive method type. Results: Data from 20,896 women were collected, of which 8,183 (39%) opted for Cu-IUD, 559 (2.5%) DPMA, and 10,989 (52.5%) chose not to use contraception at the time of hospital discharge. When comparing these groups, women in the DPMA were younger (26.5 ± 7.3, p < 0.05), and NCM showed women with a lower number of pregnancies (2.2 ± 1.3, p < 0.05). Subjects in the TL group (4.6%) had the higher number of pregnancies (3.8 ± 1.2, p < 0.05), and ENG group, the highest number of miscarriages (1.6 ± 1.3, p < 0.05). Of those women who returned pregnant, 5.5% belonged to the DPMA group, 6% to the NCM group, and 2.3% to the Cu-IUD. Conclusions: Women who opted for Cu-IUD insertion were younger, had more pregnancies and vaginal delivery when compared to those who did not choose a method. Of those women who returned, the minority opted for Cu-IUD compared to those that opted for DPMA or no method.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype.

OBJECTIVE: To report a series of atypical presentations of Aicardi-Goutières syndrome. METHODS: Clinical, neuroimaging, and genetic data. RESULTS: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). CONCLUSIONS: This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.

In Silico Screening of Inhibitors of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease.

The Venezuelan equine encephalitis virus (VEEV) nonstructural protein 2 (nsP2) cysteine protease (EC 3.4.22.B79) is essential for viral replication. High throughput in silico/in vitro screening using a focused set of known cysteine protease inhibitors identified two epoxysuccinyl prodrugs, E64d and CA074 methyl ester (CA074me) and a reversible oxindole inhibitor. Here, we determined the X-ray crystal structure of the CA074-inhibited nsP2 protease and compared it with our E64d-inhibited structure. We found that the two inhibitors occupy different locations in the protease. We designed hybrid inhibitors with improved potency. Virus yield reduction assays confirmed that the viral titer was reduced by >5 logs with CA074me. Cell-based assays showed reductions in viral replication for CHIKV, VEEV, and WEEV, and weaker inhibition of EEEV by the hybrid inhibitors. The most potent was NCGC00488909-01 which had an EC50 of 1.76 µM in VEEV-Trd-infected cells; the second most potent was NCGC00484087 with an EC50 = 7.90 µM. Other compounds from the NCATS libraries such as the H1 antihistamine oxatomide (>5-log reduction), emetine, amsacrine an intercalator (NCGC0015113), MLS003116111-01, NCGC00247785-13, and MLS00699295-01 were found to effectively reduce VEEV viral replication in plaque assays. Kinetic methods demonstrated time-dependent inhibition by the hybrid inhibitors of the protease with NCGC00488909-01 (Ki = 3 µM) and NCGC00484087 (Ki = 5 µM). Rates of inactivation by CA074 in the presence of 6 mM CaCl2, MnCl2, or MgCl2 were measured with varying concentrations of inhibitor, Mg2+ and Mn2+ slightly enhanced inhibitor binding (3 to 6-fold). CA074 inhibited not only the VEEV nsP2 protease but also that of CHIKV and WEEV.

Perfusion-Dependent Focal Neurologic Deficits in a Critically Ill Heart Transplant Recipient: A Case of Tacrolimus-Associated Reversible Cerebral Vasospasm Syndrome?

TACROLIMUS, a mainstay of immunosuppression after orthotopic heart transplantation (OHT), is associated with a broad range of side effects. Vasoconstriction caused by tacrolimus has been proposed as a mechanism underlying common side effects such as hypertension and renal injury. Neurologic side effects attributed to tacrolimus include headaches, posterior reversible encephalopathy syndrome (PRES), or reversible cerebral vasospasm syndrome (RCVS). Six case reports have been published describing RCVS in the setting of tacrolimus administration after OHT. The authors report a case of perfusion-dependent focal neurologic deficits attributed to tacrolimus-induced RCVS in an OHT recipient.

Visual Hallucinations as a Major Manifestation of Posterior Reversible Encephalopathy Syndrome: Case Report and Literature Review.

We evaluated a 48-year-old woman who had visual hallucinations (VHs) as a major presenting sign of posterior reversible encephalopathy syndrome (PRES). Despite her mild loss of vision, she described various hallucinations after awakening from a comatose state days after a motorcycle collision. VHs are usually accompanied by more severe loss of vision, yet our case and literature review indicate that sudden onset of formed VHs should suggest a possible diagnosis of PRES in patients who have large fluctuations in blood pressure, renal failure, or autoimmune dysfunction, as well as in patients taking cytotoxic agents.