Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats.

INTRODUCTION: The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. OBJECTIVES: This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. METHODS: Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 µg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. RESULTS: Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). CONCLUSIONS: The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

Highlighting early detection of thyroid pathology and gestational diabetes effects on oxidative stress that provokes preterm delivery in thyroidology: Does that ring a bell?

OBJECTIVES: Ad fontes, the status of the thyroid gland, and metabolic disturbance lead to the alteration of oxygenation. In pregnancy, it is particularly crucial to possess all predictive parameters. METHODS: This cross-sectional study was conducted at the Clinic of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Serbia, between 2017 and 2021 which study included a total of 99 women who had been admitted for preterm delivery and had undergone thyroid analysis, detected Hashimoto thyroiditis, and Oral Glucose Tolerance Test (OGTT) 40 days after delivery and had pathological Homeostatic Model Assessment for Insulin Response (HOMA IR) indices. In the group of urgent patients with preterm delivery, we looked after not only routine Doppler of the umbilical artery, but we measured specific ratios such as the Cerebroplacental ratio (CP). RESULTS: The mean maternal age was 32.23 ± 5.96 years and the mean gestational age was detected as 35.40 ± 2.39 weeks. The delivery was completed vaginally in 77 women (78%) and surgically in 22 (22%). The Mean APGAR score was 8.44 ± 1.18, the mean birth weight was 2666.87 ± 622.17g and the cases undergoing cesarean section had significantly higher values of pulsatility index (1.85 ± 0.27 vs. 1.34 ± 0.31) and CP (1.22 ± 0.26 vs. 0.47 ± 0.17). CONCLUSIONS: The introduction of Doppler sonography for blood flow assessment helps to form a complete clinical description of the patient, particularly in conditions where oxidative stress became provocative by the thyroid gland antibodies and gestational diabetes in Thyroidology.

Sociodemographic and economic characteristics of families and health and education conditions of children in the BRISA cohort during the COVID-19 pandemic.

OBJECTIVE: To describe changes in sociodemographic, economic and variables related to the characterization of family, health and education during the COVID-19 pandemic in a birth cohort evaluated at 10-11 years of age. METHODS: Cross-sectional study involving 1,033 children from a cohort of children born in 2010/2011, in the city of Ribeirão Preto, SP, Brazil. Data were collected from July to October 2021 by telephone or video interview held with the person responsible for the child. The questionnaires discussed family organization, child behavior and health, school attendance, socioeconomic assessment and occurrence of COVID-19 during the period of social isolation due to the pandemic. Descriptive statistics were used to describe the data. The chi-square test was used to verify group differences by minimum wages (MW). RESULTS: Of the respondents, 47.6% reported worsening of their financial situation during the pandemic, which was more frequent in the group with a household income <3 MW compared to the group with >6 MW (59.1 vs. 15.7%; p<0.001). According to the respondents, 62% of the children exhibited behavioral changes during the period and anxiety was the most frequently reported condition. In addition, 61.4% of the children had learning difficulties and these problems were more prevalent among children from households with lower incomes compared to those with higher incomes (74.7 vs. 45.1%; p<0.001). CONCLUSION: The COVID-19 pandemic has changed different economic aspects of families, as well as educational, health and behavioral indicators of children. Lower-income families were the most affected both economically and in terms of other indicators.

A needful, unique, and in-place evaluation of the injuries in earthquake victims with computed tomography, in catastrophic disasters! The 2023 Turkey-Syria earthquakes: part II.

OBJECTIVE: This study aimed to determine the computed tomography findings associated with very recent catastrophic 2023 Turkey-Syria earthquake-related injuries and their anatomotopographic distribution in the adult population. METHODS: The incorporated computed tomography scans of 768 adult cases who had been admitted to the hospital and had undergone computed tomography imaging after these tragic disasters had been examined on the Teleradiology Reporting System of the Turkish Ministry of Health. To this end, the injuries were classified into six categories: head, thoracic, spinal, pelvic, extremity, and abdominal injury, with three age groups (18-34, 35-64, and ³65 years) and four different imaging intervals (<24, 24-48, 49-72, and >72 h). RESULTS: This study incorporated 316 (41.1%) cases on the first day, 57 (7.5%) on the second day, 219 (28.5%) on the third day, and 176 (22.9%) on the fourth day after the earthquake or later. Of the 768 cases, 109 (14.2%) had a head injury, 100 (13.0%) had a thoracic injury, 99 (12.9%) had a spinal injury, 51 (6.6%) had a pelvic injury, 41 (5.4%) had an extremity injury, and 11 (1.4%) had an abdominal injury. CONCLUSION: In these regrettable earthquake disasters, we determined a high ratio of head injuries, which was closely followed by thoracic and spinal injuries, in our preliminary outcomes for the pediatric population, Part I. The frequency of abdominal injuries was low among individuals who experienced the earthquake. Last but not least, we have noticed a higher likelihood of spinal injury in individuals older than 65 years in the studied population.

Serum cytokines in second trimester pregnancy and their relationship with spontaneous preterm births in the Ribeirão Preto and São Luiz cohorts.

OBJECTIVE: To evaluate the association between second trimester plasma cytokine levels in asymptomatic pregnant women and preterm births (PTB) in an attempt to identify a possible predictor of preterm birth. METHODS: The study design was a nested case-control study including women with singleton a gestational age between 20-25(+ 6) weeks from two Brazilian cities. The patients were interviewed, Venous blood samples were collected. The participants were again evaluated at birth. A total of 197 women with PTB comprised the case group. The control group was selected among term births (426 patients). Forty-one cytokines were compared between groups. RESULTS: When only spontaneous PTB were analyzed, GRO, sCD40L and MCP-1 levels were lower in the case group (p < 0.05). Logarithmic transformation was performed for cytokines with discrepant results, which showed increased levels of IL-2 in the group of spontaneous PTB (p < 0.05). In both analyses, the incidence of maternal smoking and of a history of preterm delivery differed significantly between the case and control groups. In multivariate analysis, only serum GRO levels differed between the case and control groups. CONCLUSION: Lower second trimester serum levels of GRO in asymptomatic women are associated with a larger number of PTB. This finding may reflect a deficient maternal inflammatory response.

Revisiting type II diabetes mellitus in pregnancy and pregnancy outcomes such as in thyroidology: do you mind?

OBJECTIVE: There is an increase in the prevalence of pre-gestational diabetes in the past decades, mainly due to the increase in the prevalence of obesity in the general population and consequently type 2 diabetes among women of reproductive age. METHODS: This study purposed to describe the delivery characteristics, pregnancy complications, and outcomes among women in Serbia with the pre-gestational type 2 diabetes in the past decade, as well as their pregnancy complications, deliveries, and neonatal outcomes. The study included data from all the pregnant women with pre-gestational type 2 diabetes in Belgrade, Serbia during the period between 2010 and 2020. The final sample consisted of 138 patients. RESULTS: More than half, i.e., 70 (50.7%) had a vaginal delivery, while 48 (34.8%) had elective and 20 (14.5%) had emergency caesarean sections. Throughout the period, there was 1 patient with preeclampsia (0.7%), 5 with pregnancy-induced hypertension (3.6%), 7 had newborns with small for gestational age (5.1%), 28 with macrosomia (20.3%), 12 (8.7%) had preterm births, and one-fifth, i.e., 28 (20.3%) of the newborns had Apgar score under 8. CONCLUSION: The present study revealed that women with type 2 diabetes in pregnancy have a significant burden of pregnancy complications, related to pregnancy, delivery, and newborns.

Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity.

OBJECTIVE: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia. METHODS: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade. RESULTS: Gestational age at delivery (ß=-0.081, p=0.014), resistance index of the umbilical artery (ß=0.601, p=0.039), and D-dimer (ß=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966. CONCLUSION: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

Revisiting type II diabetes mellitus in pregnancy and pregnancy outcomes such as in thyroidology: do you mind?

SUMMARY OBJECTIVE: There is an increase in the prevalence of pre-gestational diabetes in the past decades, mainly due to the increase in the prevalence of obesity in the general population and consequently type 2 diabetes among women of reproductive age. METHODS: This study purposed to describe the delivery characteristics, pregnancy complications, and outcomes among women in Serbia with the pre-gestational type 2 diabetes in the past decade, as well as their pregnancy complications, deliveries, and neonatal outcomes. The study included data from all the pregnant women with pre-gestational type 2 diabetes in Belgrade, Serbia during the period between 2010 and 2020. The final sample consisted of 138 patients. RESULTS: More than half, i.e., 70 (50.7%) had a vaginal delivery, while 48 (34.8%) had elective and 20 (14.5%) had emergency caesarean sections. Throughout the period, there was 1 patient with preeclampsia (0.7%), 5 with pregnancy-induced hypertension (3.6%), 7 had newborns with small for gestational age (5.1%), 28 with macrosomia (20.3%), 12 (8.7%) had preterm births, and one-fifth, i.e., 28 (20.3%) of the newborns had Apgar score under 8. CONCLUSION: The present study revealed that women with type 2 diabetes in pregnancy have a significant burden of pregnancy complications, related to pregnancy, delivery, and newborns.

Is the length of time between endometrial scratching and embryo transfer important for pregnancy success? An observational study.

OBJECTIVE: This study sought to evaluate the influence of time (early <90 days and late >90 days) and endometrial injury on pregnancy success. METHODS: This is a retrospective study in which all infertile women who underwent at least one in vitro fertilization cycle at Clinica Gera between 2010 and 2015 were considered for inclusion. We included patients with a normal ovarian reserve and regular menses at intervals of up to 30 days. A total of 315 patient files were reviewed, and the study group was composed of patients who faced fertility issues and had male-caused infertility or idiopathic infertility. Also, women with male or unknown cause of infertility who have performed endometrial biopsy and have undergone embryo transfer up to 180 days after this procedure between 2010 and 2015 were included. The patients were divided into two groups according to the interval between biopsy and embryo transfer: group 1 (early-an interval of <90 days) and group 2 (late-an interval of >90 days and up to 180 days). RESULTS: The results were superior for the group with an interval of less than 90 days relative to the group with an interval of more than 90 days (p<0.04). The pregnancy rates for group 1 and group 2 were 58.5% and 43.4%, respectively. The odds ratio for pregnancy success was 1.63 (95% confidence interval: 1.04 to 2.55). CONCLUSION: The early transfer of embryos (<90 days) may produce better results with a high rate of pregnancy. Further studies are necessary to identify the mechanism involved in this phenomenon.

Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity

SUMMARY OBJECTIVE: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia. METHODS: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade. RESULTS: Gestational age at delivery (β=-0.081, p=0.014), resistance index of the umbilical artery (β=0.601, p=0.039), and D-dimer (β=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966. CONCLUSION: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

Is the length of time between endometrial scratching and embryo transfer important for pregnancy success? An observational study

SUMMARY OBJECTIVE: This study sought to evaluate the influence of time (early <90 days and late >90 days) and endometrial injury on pregnancy success. METHODS: This is a retrospective study in which all infertile women who underwent at least one in vitro fertilization cycle at Clinica Gera between 2010 and 2015 were considered for inclusion. We included patients with a normal ovarian reserve and regular menses at intervals of up to 30 days. A total of 315 patient files were reviewed, and the study group was composed of patients who faced fertility issues and had male-caused infertility or idiopathic infertility. Also, women with male or unknown cause of infertility who have performed endometrial biopsy and have undergone embryo transfer up to 180 days after this procedure between 2010 and 2015 were included. The patients were divided into two groups according to the interval between biopsy and embryo transfer: group 1 (early—an interval of <90 days) and group 2 (late—an interval of >90 days and up to 180 days). RESULTS: The results were superior for the group with an interval of less than 90 days relative to the group with an interval of more than 90 days (p<0.04). The pregnancy rates for group 1 and group 2 were 58.5% and 43.4%, respectively. The odds ratio for pregnancy success was 1.63 (95% confidence interval: 1.04 to 2.55). CONCLUSION: The early transfer of embryos (<90 days) may produce better results with a high rate of pregnancy. Further studies are necessary to identify the mechanism involved in this phenomenon.

Highlighting early detection of thyroid pathology and gestational diabetes effects on oxidative stress that provokes preterm delivery in thyroidology: Does that ring a bell?

Abstract Objectives: Ad fontes, the status of the thyroid gland, and metabolic disturbance lead to the alteration of oxygenation. In pregnancy, it is particularly crucial to possess all predictive parameters. Methods: This cross-sectional study was conducted at the Clinic of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Serbia, between 2017 and 2021 which study included a total of 99 women who had been admitted for preterm delivery and had undergone thyroid analysis, detected Hashimoto thyroiditis, and Oral Glucose Tolerance Test (OGTT) 40 days after delivery and had pathological Homeostatic Model Assessment for Insulin Response (HOMA IR) indices. In the group of urgent patients with preterm delivery, we looked after not only routine Doppler of the umbilical artery, but we measured specific ratios such as the Cerebroplacental ratio (CP). Results: The mean maternal age was 32.23 ± 5.96 years and the mean gestational age was detected as 35.40 ± 2.39 weeks. The delivery was completed vaginally in 77 women (78%) and surgically in 22 (22%). The Mean APGAR score was 8.44 ± 1.18, the mean birth weight was 2666.87 ± 622.17g and the cases undergoing cesarean section had significantly higher values of pulsatility index (1.85 ± 0.27 vs. 1.34 ± 0.31) and CP (1.22 ± 0.26 vs. 0.47 ± 0.17). Conclusions: The introduction of Doppler sonography for blood flow assessment helps to form a complete clinical description of the patient, particularly in conditions where oxidative stress became provocative by the thyroid gland antibodies and gestational diabetes in Thyroidology.

Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats

Abstract Introduction The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. Objectives This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. Methods Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). Conclusions The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

Sociodemographic and economic characteristics of families and health and education conditions of children in the BRISA cohort during the COVID-19 pandemic / Características sociodemográficas e econômicas das famílias e condições de saúde e educação das crianças da coorte BRISA durante a pandemia de COVID-19

ABSTRACT Objective: To describe changes in sociodemographic, economic and variables related to the characterization of family, health and education during the COVID-19 pandemic in a birth cohort evaluated at 10-11 years of age. Methods: Cross-sectional study involving 1,033 children from a cohort of children born in 2010/2011, in the city of Ribeirão Preto, SP, Brazil. Data were collected from July to October 2021 by telephone or video interview held with the person responsible for the child. The questionnaires discussed family organization, child behavior and health, school attendance, socioeconomic assessment and occurrence of COVID-19 during the period of social isolation due to the pandemic. Descriptive statistics were used to describe the data. The chi-square test was used to verify group differences by minimum wages (MW). Results: Of the respondents, 47.6% reported worsening of their financial situation during the pandemic, which was more frequent in the group with a household income <3 MW compared to the group with >6 MW (59.1 vs. 15.7%; p<0.001). According to the respondents, 62% of the children exhibited behavioral changes during the period and anxiety was the most frequently reported condition. In addition, 61.4% of the children had learning difficulties and these problems were more prevalent among children from households with lower incomes compared to those with higher incomes (74.7 vs. 45.1%; p<0.001). Conclusion: The COVID-19 pandemic has changed different economic aspects of families, as well as educational, health and behavioral indicators of children. Lower-income families were the most affected both economically and in terms of other indicators.

RESUMO Objetivo: Descrever as alterações nas características sociodemográficas, econômicas e variáveis relacionadas à caracterização da família, saúde e educação durante a pandemia da COVID-19, em uma coorte de nascimento avaliada aos 10-11 anos de idade. Métodos: Estudo transversal envolvendo 1.033 crianças de uma coorte de nascidos em 2010/2011, na cidade de Ribeirão Preto, SP, Brasil. Os dados foram obtidos por meio de entrevistas por telefone ou videochamada com o responsável pela criança, no período de julho a outubro de 2021. Os questionários abordaram informações sobre a organização familiar, comportamento e saúde da criança, acompanhamento escolar, avaliação socioeconômica e ocorrência da COVID-19 durante o período de isolamento social. Foi realizada estatística descritiva. O teste qui-quadrado foi utilizado para verificar diferenças de grupos por salários-mínimos (SM). Resultados: Dos entrevistados, 47,6% relataram piora na condição financeira durante a pandemia, sendo a piora econômica mais frequente no grupo de renda familiar <3 SM em comparação ao grupo de >6 SM (59,1 vs. 15,7%; p<0,001). Segundo os responsáveis, 62% das crianças apresentaram mudança de comportamento durante o período, sendo a ansiedade relatada com mais frequência. Ainda, 61,4% das crianças apresentaram dificuldades de aprendizagem, e o prejuízo foi mais acentuado naquelas de menor renda familiar em comparação às de maior renda (74,7 vs. 45,1%; p<0,001). Conclusão: A pandemia da COVID-19 alterou diferentes aspectos econômicos das famílias, assim como indicadores educacionais, de saúde e de comportamento das crianças. As famílias de menor renda foram as mais prejudicadas tanto do ponto de vista econômico como nos demais indicadores.

Assessment by ABPM verified the presence of hypertension in patients with self-reported hypertension, pregnant women, as well as differences between ethnicities in women aged 38-39 years in the Ribeirão Preto cohort.

Introduction: Arterial hypertension is a global health problem and one of the main risk factors for cardiovascular diseases (CVD), and therefore for morbidity and mortality among adult men and women. Factors related to obstetric history, family history, sociodemographic characteristics, and lifestyle habits are known determinants of arterial hypertension. Methods: Case-control study of women belonging to the 1978/79 birth cohort conducted in the city of Ribeirão Preto/SP. Sociodemographic data, presence of comorbidities, maternal comorbidities, paternal comorbidities, comorbidities during pregnancy, and biometric and biophysical markers associated with blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) were assessed in women aged 38-39 years. We want to study which variables of the previous sentence are related to the presence of hypertension measured by ABPM. Results: Data from 281 women were analyzed. Our results showed that ethnicity, a history of hypertension, and gestational hypertension reported by the women were significantly associated with the presence of hypertension measured by ABPM. Other factors such as marital status, educational level, comorbidities of the woman, paternal or maternal comorbidities, anthropometric measurements or serum levels of cardiovascular markers were not associated with the presence of hypertension measured by ABPM. Conclusion: We conclude that ethnicity, self-reported hypertension, and gestational hypertension are associated with arterial hypertension measured by ABPM.

Prediction and prevention of preeclampsia by physicians in Brazil: An original study.

Background: Considering the worldwide importance of preeclampsia, especially in Brazil, the screening of pregnant women at greater risk of developing the disease and the application of preventive measures are essential. This study aimed to assess the medical performance in this context in Brazil. Methods: A survey was developed to quantify the number of physicians who prescribe acetylsalicylic acid (ASA) and/or calcium for preeclampsia prevention. The survey was sent to all Brazilian obstetricians affiliated to the Brazilian Federation of OBGYN by email and WhatsApp. The survey remained opened for 6 months and included questions about the use of ASA and calcium, as well as about the use of a complementary test to predict preeclampsia. Results: The sample consisted of 360 responding physicians and 100% coverage of responses from physicians from the five different regions of Brazil was obtained. The vast majority of respondents (94.72%) prescribe ASA to prevent preeclampsia, with 80.3% prescribing a dose of 100 mg/day. Calcium is prescribed by 83.9% of the respondents. The majority of the interviewed sample (58.6%) requests uterine artery Doppler imaging to predict preeclampsia and 31.7% do not request any additional test. When the analysis was performed by region, only the northern region differed from the other Brazilian regions regarding the use of ASA and calcium for preeclampsia prevention. While more than 90% of physicians in the other regions prescribe ASA, 40% in the northern region do not use it (p < 0.0001). Regarding calcium, 30% of physicians in northern Brazil do not use the drug for preeclampsia prevention, a percentage that also differs from the other regions where the medication is prescribed by 80 to 90% of physicians (p = 0.021). Conclusions: The vast majority of Brazilian physicians prescribe low-dose aspirin and calcium carbonate to prevent preeclampsia in high-risk pregnant women. In addition to the identification of clinical risk factors, most doctors use Doppler of the uterine arteries as a predictive method. In the northern region of Brazil, physicians use aspirin and calcium less frequently for preventing preeclampsia compared to the rest of the country.