Exploring the mechanism of the reductive amination of acetophenones via the Borch approach: the role of the acid catalyst.

The energetic viability of several mechanistic variations of the reductive amination of acetophenones via the Borch approach was re-examined through density functional theory calculations. The crucial involvement of the acid catalyst is evident not only in the elimination of water, but also in the initial nucleophilic step. This role increases with the electron-donating capability of the substituent positioned at the para-position of acetophenone.

Deciphering the Absolute Configuration of Murgantiol Isomers in the Pheromone Blend of the Rice Stink Bug, Mormidea v-luteum (Hemiptera, Pentatomidae).

The males-produced pheromone blend of the Mormidea v-luteum (Hemiptera, Pentatomidae) consists in two isomers of zingiberenol (1) and three of murgantiol (2). While the absolute configuration of the zingiberenol isomers has been described, the configurations of the murgantiol isomers remained unexplored. So, our objective was to identify the absolute configuration of the murgantiol isomers (2 a-c) in the pheromone blend. To achieve this, we initially performed dehydration of the natural extract followed by enantiomeric resolution and, as a result, the three isomers was identified as (4R,1'S)-murgantiol. By leveraging the fixed cis and trans relationships among all pheromone components, we established the configuration at C-1 for isomers 2 a and 2 b is S, while that of 2 c is R. Finally, employing microchemical Sharples asymmetric dihydroxylation and epoxide ring closure, we determined the absolute configuration of the epoxide ring. Consequently, the natural isomers 2 a, 2 b, and 2 c were identified as (1S,4R,1'S,4'R)-, (1S,4R,1'S,4'S)-, and (1R,4R,1'S,4'S)-murgantiol, respectively.

Can Pheromones Contribute to Phylogenetic Hypotheses? A Case Study of Chrysomelidae.

Pheromones mediate species-level communication in the search for mates, nesting, and feeding sites. Although the role of pheromones has long been discussed by various authors, their existence was not proven until the mid-twentieth century when the first sex pheromone was identified. From this finding, much has been speculated about whether this communication mechanism has acted as a regulatory agent in the process of speciation, competition, and sexual selection since it acts as an intraspecific barrier. Chrysomelidae is one of the major Phytophaga lineages, with approximately 40,000 species. Due to this immense diversity the internal relationships remain unstable when analyzed only with morphological data, consequently recent efforts have been directed to molecular analyses to establish clarity for the relationships and found their respective monophyly. Therefore, our goals are twofold 1) to synthesize the current literature on Chrysomelidae sex pheromones and 2) to test whether Chrysomelidae sex pheromones and their chemical structures could be used in phylogenetic analysis for the group. The results show that, although this is the first analysis in Chrysomelidae to use pheromones as a phylogenetic character, much can be observed in agreement with previous analyses, thus confirming that pheromones, when known in their entirety within lineages, can be used as characters in phylogenetic analyses, bringing elucidation to the relationships and evolution of organisms.

Xylooligosaccharides: A Bibliometric Analysis and Current Advances of This Bioactive Food Chemical as a Potential Product in Biorefineries' Portfolios.

Xylooligosaccharides (XOS) are nondigestible compounds of great interest for food and pharmaceutical industries due to their beneficial prebiotic, antibacterial, antioxidant, and antitumor properties. The market size of XOS is increasing significantly, which makes its production from lignocellulosic biomass an interesting approach to the valorization of the hemicellulose fraction of biomass, which is currently underused. This review comprehensively discusses XOS production from lignocellulosic biomass, aiming at its application in integrated biorefineries. A bibliometric analysis is carried out highlighting the main players in the field. XOS production yields after different biomass pretreatment methods are critically discussed using Microsoft PowerBI® (2.92.706.0) software, which involves screening important trends for decision-making. Enzymatic hydrolysis and the major XOS purification strategies are also explored. Finally, the integration of XOS production into biorefineries, with special attention to economic and environmental aspects, is assessed, providing important information for the implementation of biorefineries containing XOS in their portfolio.

Measuring resilience and stress during pregnancy and its relation to vulnerability and pregnancy outcomes in a nulliparous cohort study.

BACKGROUND: Resilience reflects coping with pregnancy-specific stress, including physiological adaptations of the maternal organism or factors arising from the socioeconomic context, such as low income, domestic violence, drug and alcohol use, lack of a support network and other vulnerability characteristics. Resilience is a dynamic characteristic that should be comparatively evaluated within a specific context; its association with perceived stress and social vulnerability during pregnancy is still not fully understood. This study aimed at exploring maternal resilience, perceived stress and social vulnerability during pregnancy and its associated factors and outcomes. METHODS: Prospective multicenter cohort study of nulliparous women in Brazil determining resilience (Resilience Scale; RS) and stress (Perceived Stress Scale; PSS) at 28 weeks of gestation (± 1 week). Resilience and stress scores were compared according to sociodemographic characteristics related to maternal/perinatal outcomes and social vulnerability, defined as having low level of education, being adolescent, without a partner or ethnicity other than white. RESULTS: We included 383 women who completed the RS and PSS instruments. Most women showed low resilience scores (median: 124.0; IQR 98-143). Women with a low resilience score (RS < 125) were more likely from the Northeast region, adolescents, other than whites, did not study or work, had a low level of education, low family income and received public antenatal care. Higher scores of perceived stress were shown in the Northeast, other than whites, at low levels of education, low annual family income and public antenatal care. Pregnant women with low resilience scores (n = 198) had higher perceived stress scores (median = 28) and at least one vulnerability criterion (n = 181; 91.4%). CONCLUSION: Our results reinforce the role of resilience in protecting women from vulnerability and perceived stress. It may prevent complications and build a positive experience during pregnancy.

Recent advances in the synthesis of insect pheromones: an overview from 2013 to 2022.

Covering: 2013 to June 2022Pheromones are usually produced by insects in sub-microgram amounts, which prevents the elucidation of their structures by nuclear magnetic resonance (NMR). Instead, a synthetic reference material is needed to confirm the structure of the natural compounds. In addition, the provision of synthetic pheromones enables large-scale field trials for the development of environmentally friendly pest management tools. Because of these potential applications in pest control, insect pheromones are attractive targets for the development of synthetic procedures and the synthesis of these intraspecific chemical messengers has been at the core of numerous research efforts in the field of pheromone chemistry. The present review is a quick reference guide for the syntheses of insect pheromones published from 2013 to mid-2022, listing the synthesized compounds and highlighting current methodologies in organic synthesis, such as carbon-carbon coupling reactions, organo-transition metal chemistry including ring-closing olefin metathesis, asymmetric epoxidations and dihydroxylations, and enzymatic reactions.

Determination of the Absolute Configuration of the Male-Produced Sex Pheromone of the Stink Bug Pellaea stictica, (2R,4R,8R)-2,4,8,13-Tetramethyltetradecan-1-ol by Stereoselective Synthesis Coupled with Enantiomeric Resolution.

In a previous study, we reported the identification and synthesis of a male-specific sex pheromone component of the stink bug, Pellaea stictica, as the alcohol 2,4,8,13-tetramethyltetradecan-1-ol (1). To establish the correlation between the stereochemistry of the pheromone and its bioactivity, it first was necessary to determine its absolute configuration. For this purpose, a series of syntheses were designed to: (a) furnish a mixture of all possible stereoisomers; (b) a narrowed down group of diastereomers, and (c) one specific enantiomer. A crucial step in the syntheses involved a coupling reaction between two key intermediates: a phosphonium salt and an aldehyde, through a Wittig olefination. Nuclear magnetic resonance data of a mixture of the synthetic pheromone diastereomers and further comparison of GC retention times with that of the natural product by gas chromatography suggested that the methyl branches at C2 and C4 were in a syn relationship, reducing the possibilities to only four of the eight possible stereoisomers. Employing GC analysis, chiral derivatization reagents and synthetic (8R)-2,4-syn-1 it was possible to confirm the configuration of the methyl branch at C8 as R, reducing the number of possible stereoisomers to two. After enantioselective synthesis of (2R,4R,8R)-1, the absolute configurations of all methyl branches of the natural compound were confirmed as R, fully identifying the male-produced sex pheromone of P. stictica as (2R,4R,8R)-2,4,8,13-tetramethyltetradecan-1-ol.

A three-range approach enhances the prognostic utility of CSF biomarkers in Alzheimer's disease.

Introduction: Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for cerebrospinal fluid (CSF) biomarkers . Methods: With two-graph receiver-operating characteristics based on different reference schemes, we derived three-range cut-points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid-beta (Aß) positron emission tomography (PET) accumulation in non-demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n = 1246). In all analyses, we compared herein-derived three-range CSF cut-points to previously described binary ones. Results: In our main longitudinal analyses, we highlight CSF p-tau181/Aß1-42 three-range cut-points derived based on the cognitively normal Aß-PET negative versus dementia Aß-PET positive reference scheme for best depicting a prognostically relevant biomarker abnormality range. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization and a clearly abnormal group at higher risk for cognitive decline, with power analyses suggesting the latter group as potential trial enrichment candidates. Furthermore, we demonstrate that individuals with intermediate-range CSF status have similar rates of Aß deposition to those in the clearly abnormal group. Discussion: The proposed approach can refine clinico-biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker-related cognitive decline in comparison to binary cut-points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.

Long-Term Symptoms among COVID-19 Survivors in Prospective Cohort Study, Brazil.

We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.

Agreement between the short and long versions of the Resilience Scale: A validation among the obstetric population according to vulnerability status.

OBJECTIVE: To compare the 14-item Resilience Scale (RS-14) and the original 25-item scale (RS-25) in the obstetric population, including vulnerable and non-vulnerable women. METHODS: A Brazilian prospective cohort study was conducted of nulliparous singleton pregnant women from March 2018 to March 2020. Women who completed the RS-25 at 27-29 weeks of pregnancy were included in the analysis. RS-25 and RS-14 scores were converted to comparable scales of 0-100. Medians, standard deviations, and centiles between versions were compared for the general, vulnerable, and non-vulnerable populations. Correlation, concordance, and internal consistency and reliability analyses were performed. P < 0.05 was considered statistically significant. RESULTS: In total, 381 women who completed the RS-25 were included. Medians of RS-14 and RS-25 scores were significantly different (73.4 and 70.8, respectively; P < 0.001), regardless of the vulnerability status. The RS-14 showed a high correlation (Pearson´s correlation coefficient of -0.379 (P-value < 0.001)), but no agreement (Pitman's test of difference in variance: r = 0.422; P < 0.001) with the RS-25 version. RS-14 showed high internal consistency and reliability with only one component (Variance of 59.82%, Cronbach's Alpha 0.947). CONCLUSION: The RS-14 may overestimate the RS-25 score and different domains may not be assessed by the short version. The psychometric properties of the RS-14 and the clinical relevance of the variation between versions require further evaluation.

Transsylvian amygdalohippocampectomy for mesial temporal lobe epilepsy: Comparison of three different approaches.

OBJECTIVE: This study's objective was to compare the transinsular (TI-AH), transuncus (TU-AH), and temporopolar (TP-AH) amygdalohippocampectomy approaches regarding seizure control, temporal stem (TS) damage, and neurocognitive decline. METHODS: We included 114 consecutive patients with unilateral hippocampal sclerosis (HS) who underwent TI-AH, TU-AH, or TP-AH between 2002 and 2017. We evaluated seizure control using Engel classification. We used diffusion tensor imaging and postoperative Humphrey perimetry to assess the damage of the TS. We also performed pre- and postoperative memory performance and intelligence quotient (IQ). RESULTS: There were no significant differences in the proportion of patients free of disabling seizures (Engel IA+IB) among the three surgical approaches in the survival analysis. However, more patients were free of disabling seizures (Engel IA+IB) at 2 years of postsurgical follow-up with TP-AH (69.5%) and TI-AH (76.7%) as compared to the TU-AH (43.5%) approach (p = .03). The number of fibers of the inferior fronto-occipital fasciculus postoperatively was reduced in the TI-AH group compared with the TU-AH and TP-AH groups (p = .001). The rate of visual field defects was significantly higher with TI-AH (14/19, 74%) in comparison to the TU-AH (5/15, 33%) and TP-AH (13/40, 32.5%) approaches (p = .008). Finally, there was a significant postoperative decline in verbal memory in left-sided surgeries (p = .019) and delayed recall for both sides (p < .001) regardless of the surgical approach. However, TP-AH was the only group that showed a significant improvement in visual memory (p < .001) and IQ (p < .001) for both right- and left-sided surgeries. SIGNIFICANCE: The TP-AH group had better short-term seizure control than TU-AH, a lower rate of visual field defects than TI-AH, and improved visual memory and IQ compared to the other groups. Our findings suggest that TP-AH is a better surgical approach for temporal lobe epilepsy with HS than TI-AH and TU-AH.

Analgesia for vaginal birth: Secondary analysis from the WHO Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To evaluate the use of analgesia during labor in women who had a vaginal birth and to determine the factors associated with its use. METHODS: A secondary analysis was performed of the WHO Multicountry Survey on Maternal and Newborn Health, a cross-sectional, facility-based survey including 359 healthcare facilities in 29 countries. The prevalence of analgesia use for vaginal birth in different countries was reported according to the Human Development Index (HDI). Sociodemographic and obstetric characteristics of the participants with and without analgesia were compared. The prevalence ratios were compared across countries, HDI groups, and regions using a design-based χ2 test. RESULTS: Among the 221 345 women who had a vaginal birth, only 4% received labor analgesia, mainly epidural. The prevalence of women receiving analgesia was significantly higher in countries with a higher HDI than in countries with a lower HDI. Education was significantly associated with increased use of analgesia; nulliparous women and women undergoing previous cesarean delivery had a significantly increased likelihood of receiving analgesia. CONCLUSION: Use of analgesia for women undergoing labor and vaginal delivery was low, specifically in low-HDI countries. Whether low use of analgesia reflects women's desire or an unmet need for pain relief requires further studies.

Maternal BMI at the time of birth and selected risk factors associated with severe neonatal outcomes: a secondary analysis of the WHO Better Outcomes in Labour Difficulty (BOLD) project.

The main objective of this secondary analysis was to describe the nutritional status of the Better Outcomes in Labour Difficulty (BOLD) project study population and determine possible associations between maternal nutritional status (as reflected by maternal BMI at the time of birth) and severe neonatal outcomes (SNO). We also analysed previous and index maternal pathologies to determine associations with neonatal outcomes. We used the classification designed by Atalah for maternal BMI and compared with the Hyperglycaemia and Adverse Pregnancy Outcome study one. To describe the nutritional status of this population, figures of distribution and test of normality related to weight and BMI were presented for the women and their babies. To explore the association between maternal BMI data and SNO, the χ2 test was performed. To identify a maternal characteristic or a group of characteristics that could predict SNO, we used Fisher's exact test using previous maternal pathology collected in the BOLD project as well as that in the index pregnancy. In this study, BMI at the time of birth was not associated with neonatal near miss or death. We found that previous maternal obesity, diabetes and chronic hypertension were associated with SNO. Maternal pathology in the index pregnancy such as other obstetric haemorrhage, pre-eclampsia, anaemia and gestational diabetes was associated with SNO.

Provision of intensive care to severely ill pregnant women is associated with reduced mortality: Results from the WHO Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To estimate the impact of the use of Intensive Care Units (ICU) in maternal mortality. METHODS: A secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health, a multicenter cross-sectional study conducted in maternity hospitals in 29 countries. Women who had severe maternal outcome (maternal death or maternal near-miss) and the availability and use of ICU beds were included. The women were categorized according to availability of ICU, and multivariate logistic regression analyses were performed to determine the risk of maternal death. To rate the severity of complications, the Maternal Severity Score (MSS) and the Maternal Severity Index (MSI) were used. RESULTS: Of 314 623 women observed, 24 396 had severe complications. Of those, 16 981 (69.6%) were in facilities with ICUs; 1573 women were admitted to ICUs (6.4% of women with maternal complications and 0.5% of total). There is a significant protective effect for maternal mortality for patients with more severe conditions using ICUs (odds ratio 0.16, 95% confidence interval 0.07-0.33). CONCLUSION: The use of ICU was associated with significantly reduced odds of maternal death in obstetric patients with severe clinical conditions. The availability and appropriate use of good-quality ICUs are therefore crucial to reduce maternal mortality.

Postpartum hemorrhage care bundles to improve adherence to guidelines: A WHO technical consultation.

OBJECTIVE: To systematically develop evidence-based bundles for care of postpartum hemorrhage (PPH). METHODS: An international technical consultation was conducted in 2017 to develop draft bundles of clinical interventions for PPH taken from the WHO's 2012 and 2017 PPH recommendations and based on the validated "GRADE Evidence-to-Decision" framework. Twenty-three global maternal-health experts participated in the development process, which was informed by a systematic literature search on bundle definitions, designs, and implementation experiences. Over a 6-month period, the expert panel met online and via teleconferences, culminating in a 2-day in-person meeting. RESULTS: The consultation led to the definition of two care bundles for facility implementation. The "first response to PPH bundle" comprises uterotonics, isotonic crystalloids, tranexamic acid, and uterine massage. The "response to refractory PPH bundle" comprises compressive measures (aortic or bimanual uterine compression), the non-pneumatic antishock garment, and intrauterine balloon tamponade (IBT). Advocacy, training, teamwork, communication, and use of best clinical practices were defined as PPH bundle supporting elements. CONCLUSION: For the first response bundle, further research should assess its feasibility, acceptability, and effectiveness; and identify optimal implementation strategies. For the response to refractory bundle, further research should address pending controversies, including the operational definition of refractory PPH and effectiveness of IBT devices.

Analgesia during Labor and Vaginal Birth among Women with Severe Maternal Morbidity: Secondary Analysis from the WHO Multicountry Survey on Maternal and Newborn Health.

AIM: To evaluate the use of analgesia for vaginal birth, in women with and without severe maternal morbidity (SMM) and to describe sociodemographic, clinical, and obstetric characteristics and maternal and perinatal outcomes associated with labor analgesia. METHODS: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHO-MCS), a global cross-sectional study performed between May 2010 and December 2011 in 29 countries. Women who delivered vaginally and had an SMM were included in this analysis and were then divided into two groups: those who received and those who did not receive analgesia for labor/delivery. We further compared maternal characteristics and maternal and perinatal outcomes between these two groups. RESULTS: From 314,623 women originally included in WHO-MCS, 9,788 developed SMM and delivered vaginally, 601 (6.1%) with analgesia and 9,187 (93.9%) without analgesia. Women with SMM were more likely to receive analgesia than those who did not experience SMM. Global distribution of SMM was similar; however, the use of analgesia was less prevalent in Africa. Higher maternal education, previous cesarean section, and nulliparity were factors associated with analgesia use. Analgesia was not an independent factor associated with an increase of severe maternal outcome (Maternal Near Miss + Maternal Death). CONCLUSIONS: The overall use of analgesia for vaginal delivery is low but women with SMM are more likely to receive analgesia during labor. Social conditions are closely linked with the likelihood of having analgesia during delivery and such a procedure is not associated with increased adverse maternal outcomes. Expanding the availability of analgesia in different levels of care should be a concern worldwide.

Perinatal outcomes in twin pregnancies complicated by maternal morbidity: evidence from the WHO Multicountry Survey on Maternal and Newborn Health.

BACKGROUND: Twin pregnancy was associated with significantly higher rates of adverse neonatal and perinatal outcomes, especially for the second twin. In addition, the maternal complications (potentially life-threatening conditions-PLTC, maternal near miss-MNM, and maternal mortality-MM) are directly related to twin pregnancy and independently associated with adverse perinatal outcome. The objective of the preset study is to evaluate perinatal outcomes associated with twin pregnancies, stratified by severe maternal morbidity and order of birth. METHODS: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), a cross-sectional study implemented in 29 countries. Data from 8568 twin deliveries were compared with 308,127 singleton deliveries. The occurrence of adverse perinatal outcomes and maternal complications were assessed. Factors independently associated with adverse perinatal outcomes were reported with adjusted PR (Prevalence Ratio) and 95%CI. RESULTS: The occurrence of severe maternal morbidity and maternal death was significantly higher among twin compared to singleton pregnancies in all regions. Twin deliveries were associated with higher rates of preterm delivery (37.1%), Apgar scores less than 7 at 5th minute (7.8 and 10.1% respectively for first and second twins), low birth weight (53.2% for the first and 61.1% for the second twin), stillbirth (3.6% for the first and 5.7% for the second twin), early neonatal death (3.5% for the first and 5.2% for the second twin), admission to NICU (23.6% for the first and 29.3% for the second twin) and any adverse perinatal outcomes (67% for the first twin and 72.3% for the second). Outcomes were consistently worse for the second twin across all outcomes. Poisson multiple regression analysis identified several factors independently associated with an adverse perinatal outcome, including both maternal complications and twin pregnancy. CONCLUSION: Twin pregnancy is significantly associated with severe maternal morbidity and with worse perinatal outcomes, especially for the second twin.

Acclimation responses of macaw palm seedlings to contrasting light environments.

The photosynthetic adjustments of macaw palm (Acrocomia aculeata) were evaluated in 30-day-old seedlings exposed to high and low light environments, and sudden transference from low to high light and comparisons were made with the hardening protocol used in nurseries. Furthermore, we evaluated the responses to long-term exposure (265 days) to high and low light environments. Macaw palm seedlings exhibited an efficient mechanism that maximized light capture under scarce conditions, and dissipated excess energy to avoid damaging to the photosystem II under high light. The seedlings showed low saturation irradiance but no photoinhibition when exposed to excess light. When grown under low light intensities, seedlings presented higher photochemical efficiency and minimized the respiratory costs with positive carbon balance at lower irradiance than hardened seedlings did. The hardening procedure did not appear to be an advantageous method during seedling production. Long-term exposure to either low or high light did not cause significant leaf anatomical adjustments. However, the low light seedlings showed higher leaf area and chlorophyll content than those exposed to higher light intensity did, which enabled shaded seedlings to maximize the captured light. Furthermore, the high non-photochemical dissipation allowed rapid acclimation to excessive light exposure. These responses allow macaw palm cultivation and establishment in very different light environments.

Increases in Caesarean Delivery Rates and Change of Perinatal Outcomes in Low- and Middle-Income Countries: A Hospital-Level Analysis of Two WHO Surveys.

BACKGROUND: Maternal and neonatal outcomes have improved substantially. During the same period, the caesarean delivery rate soared. The aim of this analysis was to determine whether an increase in caesarean rate was associated with an improvement in perinatal outcome at an institutional level in low- and middle-income countries. METHODS: The WHO Global Survey on Maternal and Perinatal Health (WHOGS) and the WHO Multi-Country Survey on Maternal and Newborn Health (WHOMCS) were two multi-country, facility-based, cross-sectional surveys conducted in 2004-08 and 2010-11, respectively. The increase in caesarean rate and the change of prevalence of adverse perinatal outcomes were calculated using a two-point estimator of percent change annualized (PCA) method. Maternal, perinatal, and neonatal composite indexes were used as the outcomes. A linear mixed model was used to assess the association between the change of caesarean rate and the change of perinatal outcome. RESULTS: A total of 259 facilities in 20 countries participated in both surveys, with 217 844 women in WHOGS and 227 734 women in WHOMCS. The caesarean rate in these facilities increased, on average, by 4.0% annually, while the prevalence of adverse perinatal outcomes decreased by 4.6% annually. However, after adjustments for potential confounders, no association was found between the increase in caesarean rate and the change of adverse outcome indexes, regardless of whether starting caesarean rates were already high (above 10%) or not. CONCLUSIONS: In low- and middle-income countries, the increases in caesarean rates were not associated with improved perinatal outcomes regardless of whether the starting caesarean rate was already high or not.