Temporal trends and spatial clusters of high risk for maternal death due to COVID-19 pre and during COVID-19 vaccination in Brazil: a national population-based ecological study.

OBJECTIVE: This study comprehensively analyzed the temporal and spatial dynamics of COVID-19 cases and deaths within the obstetric population in Brazil, comparing the periods before and during mass COVID-19 vaccination. We explored the trends and geographical patterns of COVID-19 cases and maternal deaths over time. We also examined their correlation with the SARS-CoV-2 variant circulating and the social determinants of health. STUDY DESIGN: This is a nationwide population-based ecological study. METHODS: We obtained data on COVID-19 cases, deaths, socioeconomic status, and vulnerability information for Brazil's 5570 municipalities for both the pre-COVID-19 vaccination and COVID-19 vaccination periods. A Bayesian model was used to mitigate indicator fluctuations. The spatial correlation of maternal cases and fatalities with socioeconomic and vulnerability indicators was assessed using bivariate Moran. RESULTS: From March 2020 to June 2023, a total of 23,823 cases and 1991 maternal fatalities were recorded among pregnant and postpartum women. The temporal trends in maternal incidence and mortality rates fluctuated over the study period, largely influenced by widespread COVID-19 vaccination and the dominant SARS-CoV-2 variant. There was a significant reduction in maternal mortality due to COVID-19 following the introduction of vaccination. The geographical distribution of COVID-19 cases and maternal deaths exhibited marked heterogeneity in both periods, with distinct spatial clusters predominantly observed in the North, Northeast, and Central West regions. Municipalities with the highest Human Development Index reported the highest incidence rates, while those with the highest levels of social vulnerability exhibited elevated mortality and fatality rates. CONCLUSION: Despite the circulation of highly transmissible variants of concern, maternal mortality due to COVID-19 was significantly reduced following the mass vaccination. There was a heterogeneous distribution of cases and fatalities in both periods (before and during mass vaccination). Smaller municipalities and those grappling with social vulnerability issues experienced the highest rates of maternal mortality and fatalities.

Ingestive behavior of lambs confined in individual and group stalls.

The experiment was conducted to evaluate the ingestive behavior of lambs confined in individual and group stalls. We used thirty-four lambs in their growing phase, aged an average of three months, with mean initial live weight of 17.8±5.2 kg. They were allotted in a completely randomized design with 24 animals kept in individual stalls and 10 animals confined as a group. The experiment lasted for a total of 74 days, and the first 14 days were dedicated to the animals' adaption to the management, facilities and diets. The data collection period lasted 60 days, divided into three 20-d periods for the behavior evaluation. The animals were subjected to five days of visual observation during the experiment period, by the quantification of 24 h a day, with evaluations on the 15th day of each period and an interim evaluation consisting of two consecutive days on the 30th and 31st day of the experiment. The animals confined as a group consumed less (p<0.05) fiber. However, the animals confined individually spent less (p<0.05) time on feeding, rumination and chewing activities and longer in idleness. Therefore, the lower capacity of lambs confined in groups to select their food negatively affects their feeding behavior.

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages.

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17ß-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions.

Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.

Penicillium piceum infection: diagnosis and successful treatment in chronic granulomatous disease.

Infections due to Penicillium species other than P.marneffei are rare. We identified a boy with X-linked chronic granulomatous disease (X-CGD) with a pulmonary nodule and adjacent rib osteomyelitis caused by Penicillium piceum. The only sign of infection was an elevated sedimentation rate. P. piceum was isolated by fine needle aspirate and from excised infected tissues. Surgical removal and one year of voriconazole treatment were very well tolerated and led to complete recovery. Microbiological, microscopic and molecular studies support the fungal diagnosis. P. piceum should be considered as a relevant pathogen in immunocompromised patients.

Effects of intracellular calcium elevation on action potential and L-type calcium current of normal and chronically infarcted rat ventricles.

The present work investigated the effects of raising [Ca+2]i levels on action potential (AP) and L-type calcium current (I(Ca.L)) of normal and chronically infarcted rat ventricles. Experiments were performed by conventional electrophysiology and whole-cell patch-clamp techniques. In the former, APs were recorded in ventricular strips subjected to different pacing rates or elevation of [Ca+2]o levels. In the latter, I(Ca.L) was studied in isolated myocytes in the absence of an intracellular Ca+2 chelator. The acceleration of heart rate (6 to 240 beats/min) reduced AP duration measured at 20%, 50%, and 90% repolarization (APD20, APD50, and APD90) in the infarcted group, and increased APD20 and APD50 in the control group. Rising [Ca+]o (1.25 to 5.0 mmol/L) induced a decrease of APD20 and APD50 in both groups. Voltage clamp revealed a smaller I(Ca.L) density at approximately -17 mV in myocytes from infarcted ventricles (-1.86 +/- 0.37 vs -3.98 +/- 0.65 pA/pF, P < .05), and the appearance of a non-K+ outward current coupled to I(Ca.L). The results suggest the participation of a Ca+2-activated outward current in the repolarization of normal and infarcted rat ventricles.

[Fungal infections in paediatric patients with chronic granulomatous disease]. / Infecciones fúngicas en pacientes pediátricos con enfermedad granulomatosa crónica.

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting from a disfunction of microbial capacity of phagocytes. Patients with this disease show great susceptibility to fungal and bacterial infections. Between 1988 and 1998, five paediatric patients with CGD who acquired mycotic infections were studied at the Paediatric Hospital Prof. Dr. J. P. Garrahan and their clinical and microbiological characteristics were described. The fungal infection appeared at the mean-age of 8.3 years (range: 1.1-17 years). All the patients had fever and lung involvement, three of them had suppurative abscesses of soft tissues. The mycological diagnosis was determined by microscopy, culture of clinical samples and serologic tests. There were three cases of disseminated aspergillosis, two cases of mixed infection: one due to Candida albicans and Nocardia asteroides and the other due to Scedosporium apiospermum and Cladosporium spp. Four out of the 5 patients died because of an infections process beyond control. Our conclusion is that new therapeutic measures must be considered along with the study of emerging pathogens in this group of patients.

Ventricular action potential and L-type calcium channel in infarct-induced hypertrophy in rats.

INTRODUCTION: The present investigation was aimed at characterization of: (1) action potential parameters; and (2) L-type calcium channels in the hypertrophied ventricular tissue surviving an extensive healed myocardial infarction in the rat. METHODS AND RESULTS: Myocardial infarction was produced in Wistar rats by ligation of the left coronary artery. One to 2 months later, their hearts were subjected to electrophysiologic study. The main difference in subendocardial transmembrane potentials recorded with intracellular microelectrodes was an increase in action potential duration (APD). In the left ventricle, the infarcted/sham-operated APD ratio ranged from 2.7 to 7.2, whereas in the right ventricle it ranged from 1.6 to 2.3 in different regions. When compared with control cells, ventricular myocytes from infarcted hearts were found to be larger (P < 0.01) and showed a reduction (P < 0.05) in L-type calcium current (LCa,L) density obtained by whole cell, patch clamp (at 0 mV: 4.44 +/- 0.41 in infarcted vs 8.03 +/- 1.22 pA/pF in normal). The time course of decay of the currents could be fitted by two exponential functions in both normal and infarcted hearts. There was a tendency toward an increase in the time constant of the slower component of inactivation, tau 2, significant only at +20 mV (215 +/- 25 vs 151 +/- 15 msec). CONCLUSIONS: Cardiac hypertrophy of healed infarction in rats is associated with lengthening of the action potential in both ventricles. The main alteration observed in ICa,L was a decrease in the current density. Thus, alteration of the calcium channel is not the determinant factor of APD increase.

Traumatismo de veia cava inferior: análise de 36 casos / Inferior vena cava trauma: analysis of 36 cases

Os autores analisaram 36 casos de traumatismos de veia cava inferior (VCI), a fim de avaliar as formas de tratamento empregadas, bem como os principais aspectos relacionados às altas taxas de morbidade e mortalidade freqüentemente encontradas nesse tipo de lesäo. Os projéteis de arma de fogo foram os agentes lesivos mais comuns, e 55// dos doentes tinham algum grau de instabilidade circulatória à admissäo. A porçäo retro-hepática foi a mais freqüentemente atingida e o fígado, o órgäo mais lesado em associaçäo à lesäo venosa. Dos vinte doentes admitidos com instabilidade hemodinâmica, 17 morreram e, desses, a lesäo era na porçäo retro-hepática em nove e na porçäo supradiafragmática em três, confirmando que a localizaçäo da lesäo e a instabilidade circulatória à admissäo säo os dois fatores mais importantes com relaçäo ao prognóstico pós-operatório

[Inferior vena cava trauma: analysis of 36 cases]. / Traumatismo de veia cava inferior: análise de 36 casos.

The authors analysed 36 trauma patients with inferior vena cava injuries to evaluate different surgical approaches, as well as, important aspects related to morbidity and mortality. Gunshot wounds were the most frequent cause of inferior vena cava injuries and 55% of the patients had circulatory instability on admission. Retrohepatic inferior vena cava was frequently injured in association with liver injury. From those 20 unstable patients on admission, there were 17 deaths, and injury was in the retrohepatic portion of the inferior vena cava in 9, and in the supradiaphragmatic portion in 3. These data support the concept that site of injury and hemodynamic status on admission are the principal factors related to morbidity and mortality in inferior vena cava injuries.

The electrocardiogram of rats with an old extensive myocardial infarction.

The electrocardiographic alterations of old murine myocardial infarction have not been well characterized. In the present study, adult Wistar rats of both sexes were infarcted by left coronary artery ligation and the electrocardiogram was recorded 1 to 11 months later. When compared to sham-operated rats, animals with large infarcts, identified on the basis of extensive transmural scars, showed (P less than 0.01) a marked rightward deviation of the QRS axis (+125.3 degrees +/- 34.3 degrees vs +59.9 degrees +/- 15.9 degrees), a high incidence of Q waves (88% vs 0% in classic lead 1), a decrease in QRS amplitude index (0.66 +/- 0.31 mV vs 1.00 +/- 0.23 mV), a discrete increase in PR interval (58 +/- 7 ms vs 53 +/- 5 ms) and greater P wave amplitude. The present results show that the electrocardiogram (EKG) is a reliable tool for diagnosis of old extensive infarctions in rats.

The electrocardiogram of rats with an old extensive myocardial infarction

The electrocardiographic alterations of old murine myocardial infarction have not been well characterized. In the present study, adult Wistar rats, of both sexes were infarcted by left coronary artery ligation and the electrocardiogram was recorded 1 to 11 months later. When compared to sham-operated rats, animals with large infarcts, identified on the basis of extensive transmural scars, showed (P<0.01) a marked rightward deviation of the QRS axis (+125.3- ñ 34.3- vs 59.99- ñ 15.9-), a high incidence of Q waves (88% vs 0% in classic lead 1), a decrease in QRS amplitude index (0.66 ñ 0.31 mV vs 1.00 ñ 0.23 mV), a discrete increse in PR interval (58 ñ 7 ms vs 53 ñ 5ms) and greater P wave amplitude. The present results show that the electrocardiogram (EKG) is a reliable tool for diagnosis of old extensive infarctions in rats

Effects of crotoxin on the isolated guinea pig heart.

The effects of crotoxin, isolated from the venom of the South American rattlesnake, Crotalus durissus terrificus, were investigated on isolated guinea pig hearts, perfused with Locke solution, by the Langendorff method. The cardiac beats and the electrocardiogram were simultaneously registered and the creatine kinase (CK) activity of the perfusate measured. Crotoxin was infused (4.5 x 10(-8) M and 2.3 x 10(-7) M) into the heart during 90 min, and induced a remarkable decrease in the contractile force, without a significant reduction of heart rate, increased the P-R interval and displaced the S-T segment. The activity of CK only increased in the late phases of the experiments, when the force of contraction was below 25% of the control value. Arrhythmias were uncommon and no alterations of QRS duration or Q-Tc interval were observed. The reduction of the contractile force and the increase in CK activity were completely prevented by bovine serum albumin, whereas lanatoside C did not interfere with the toxin action. A bolus injection of crotoxin (11 +/- 2 nmoles) also induced a decrease of contractile force without reduction of heart rate. This decrease of force was partially prevented by indomethacin, but not by atropine. It is suggested that the reduction of contractile force evoked by crotoxin is due probably to release of free fatty acids and lysophospholipids (initial effect) and to a cellular lesion (late effect).

Oscillations of cardiac rate induced by acetylcholine in the isolated guinea pig heart.

1. The effects of acetylcholine (ACh) on cardiac rate (electrocardiogram), contractile force and coronary flow recorded simultaneously were investigated in isolated guinea pig hearts perfused with Locke solution by the method of Langendorff. 2. Bolus injections of 0.5-550 nmol ACh induced oscillations of cardiac rate. These changes were not directly related to the doses of ACh injected (chi 2 test, P greater than 0.05). 3. The presence of 10 microM physostigmine in the Locke solution increased the number of heart rate oscillations elicited by ACh. 4. The electrocardiogram showed that the heart rate oscillations were due to wandering pacemakers, such as slow or fast junctional rhythm, and slow or fast idioventricular rhythm, which were intermingled with sinus rhythm, A-V block or sinus bradycardia. 5. In most experiments, the increase in ventricular rate was associated with an increase in ventricular contractile force ("Bowditch Effect") and a simultaneous reduction of coronary flow. 6. The heart rate oscillations were not prevented by reserpine or blockade of nicotinic receptors (hexamethonium plus gallamine) but were prevented by blockade of muscarinic receptors with atropine. 7. We conclude that the heart rate oscillations induced by ACh are due to several electrophysiological mechanisms (automatism and/or conduction disturbances) related to activation of muscarinic receptors.

Oscillations of cardiac rate induced by acetylcholine in the isolated guinea pig heart

1. The effects of acetylcholine (ACh) on cardiac rate (electrocardiogram), contractile force and coronary flow recorded simultaneously were investigated in isolated guinea pig hearts perfused with Locke solution by the method of Langendorff. 2. Bolus injections of 0.5-550 nmol ACh induced oscillations of cardiac rate. These changes were not directly related to the doses of ACh injected (X**2 test, P > 0.05). 3. The presence of 10 micronM physostigmine in the Locke solution increased the number of heart rate oscillations elicited by ACh. 4. The electrocardiogram showed that the heart rate oscillations were due to wandering pacemakers, such as slow or fast junctional rhythm, and slow or fast indioventricular rhythmy, which were intermingled with sinus rhythym, A - V block or sinus bradycardia. 5. In most experiments, the increase in ventricular rate was associated with an increase in ventricular contractile force ("Bowditch Effect") and a simultaneous reduction of coronary flow. 6. The heart rate oscillations were not prevented bu reserpine or blockade of nicotinic receptors (hexamethonium plus gallamine) but were prevented blockade of muscarinic receptors with atropine. 7. We conclude that the heart rate oscillations induced by ACh are due to several electrophysiological mechanisms (automatism and/or conduction disturbances_ related to activation of muscarinic receptors