Role of fetal head-circumference-to-maternal-height ratio in predicting Cesarean section for labor dystocia: prospective multicenter study.

OBJECTIVE: To evaluate the relationship between the fetal head-circumference-to-maternal-height (HC/MH) ratio measured shortly before delivery and the occurrence of Cesarean section (CS) for labor dystocia. METHODS: This was a multicenter prospective cohort study involving four tertiary maternity hospitals. An unselected cohort of women with a singleton fetus in cephalic presentation, at a gestational age beyond 36 + 0 weeks and without any contraindication for vaginal delivery, was enrolled between September 2020 and November 2021. The MH and fetal HC were measured on admission of the patient to the labor ward. The primary outcome of the study was the performance of the HC/MH ratio in the prediction of CS for labor dystocia. Women who underwent CS for any indication other than failed labor progression, including fetal distress, were excluded from the final analysis. RESULTS: A total of 783 women were included in the study. Vaginal delivery occurred in 744 (95.0%) women and CS for labor dystocia in 39 (5.0%). CS for labor dystocia was associated with shorter MH (mean ± SD, 160.4 ± 6.6 vs 164.5 ± 6.3 cm; P < 0.001), larger fetal HC (339.6 ± 9.5 vs 330.7 ± 13.0 mm; P < 0.001) and a higher HC/MH ratio (2.12 ± 0.11 vs 2.01 ± 0.10; P < 0.001) compared with vaginal delivery. Multivariate logistic regression analysis showed that the HC/MH ratio was associated independently with CS for labor dystocia (adjusted odds ratio, 2.65 (95% CI, 1.85-3.79); P < 0.001). The HC/MH ratio had an area under the receiver-operating-characteristics curve of 0.77 and an optimal cut-off value for discriminating between vaginal delivery and CS for labor dystocia of 2.09, which was associated with a sensitivity of 0.62 (95% CI, 0.45-0.77), specificity of 0.79 (95% CI, 0.76-0.82), positive predictive value of 0.13 (95% CI, 0.09-0.19) and negative predictive value of 0.98 (95% CI, 0.96-0.99). CONCLUSIONS: In a large cohort of unselected pregnancies, the HC/MH ratio performed better than did fetal HC and MH alone in identifying those cases that will undergo CS for labor dystocia, albeit with moderate predictive value. The HC/MH ratio could assist in the evaluation of women at risk for CS for labor dystocia. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Daratumumab plus bortezomib or daratumumab plus lenalidomide as salvage therapy for patients with myeloma: initial follow-up of an Italian multicentre retrospective clinical experience by 'Rete Ematologica Pugliese'.

We report herein a multicentre retrospective analysis of 192 consecutive patients with symptomatic refractory/relapsed multiple myeloma (RRMM) treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centres in Puglia. Choice of both regimens was based on previous treatment and/or physicians' preference. Considering the under-representation of older patients (very old patient ≥ 80 years) in clinical trials and the prognostic and predictive importance and value of frailty status, here, we further characterised the patient cohort by age. The overall response rate (ORR) was generally lower than what was previously reported in the CASTOR (ORR 72.6% vs 85%) and POLLUX (ORR 86.5% vs 93%) trials. The lower ORR in our analysis compared to the CASTOR and POLLUX trials could be related to a less selected population. Similarly, amongst very old patients, the ORR was encouraging: ORR to treatment with DVd (daratumumab + bortezomib + dexamethasone) was 66.7%, and ORR to treatment with DRd (daratumumab + lenalidomide + dexamethasone) was 92.3%. Median TTP (time to progression) was 10.8 months (1-year TTP: 44.7%; 2-year TTP: 25.3%) in the DVd group; median TTP was not reached in the DRd group (1-year TTP: 82.7%; 2-year TTP: 71.4%). Median OS (overall survival) was not reached either in the DRd group (1-year OS: 85.9%; 2-year OS: 73.7%) or the DVd group (1-year OS: 70.2%; 2-year OS: 58.9%).

External validation of a simple risk score based on the ASPRE trial algorithm for preterm pre-eclampsia considering maternal characteristics in nulliparous pregnant women: a multicentre retrospective cohort study.

OBJECTIVE: To validate the performance of a first-trimester simple risk score based on the ASPRE trial algorithm for pre-eclampsia. DESIGN: Multicentre retrospective cohort analysis. SETTING: Four Italian hospitals. POPULATION: Unselected nulliparous women at 11-13 weeks of gestation from January 2014 through to January 2018. METHODS: Model performance was evaluated based on discrimination and calibration. MAIN OUTCOME MEASURES: Delivery before 37 weeks of gestation with a diagnosis of pre-eclampsia. RESULTS: Based on 73 preterm pre-eclampsia cases and 7546 controls (including 101 cases of late pre-eclampsia), the area under the receiver operating characteristics curve was 0.659 (95% CI 0.579-0.726). The sensitivity was 32.9% (95% CI 22.1-43.7) at a false-positive rate of 8.8%. The positive likelihood ratio was 3.74 (95% CI 2.67-5.23), the positive predictive value was 3.49% (95% CI 2.12-4.86%) and the negative predictive value was 99.3% (95% CI 99.1-99.5%). The sensitivity and positive likelihood ratio were approximately 40% lower than in the original study. The calibration analysis showed a good agreement between observed and expected risks (P = 0.037). Comparison with the Fetal Medicine Foundation (FMF) algorithm yielded a difference in the area under the curve of 0.084 (P = 0.007). CONCLUSIONS: In our Italian population, the simple risk score had a lower performance than expected for the prediction of preterm pre-eclampsia in nulliparous women. The FMF algorithm applied to the same data set resulted in a better prediction. TWEETABLE ABSTRACT: Simple risk score predicts preterm pre-eclampsia in Italy.

Interleukin-1 gene polymorphisms and toxoplasmic retinochoroiditis.

PURPOSE: It has been proposed that cytokine gene polymorphisms can predispose individuals to disease by enhancing inflammatory processes. Considering the relevance of interleukin-1 (IL-1) in the pathogenesis of toxoplasmic retinochoroiditis (TR), we investigated whether IL1A -889 C/T and IL1B +3954C/T promoter polymorphisms are associated with TR in humans. METHODS: We performed a cross-sectional study that involved 100 Brazilian TR patients and 100 age- and gender-matched control subjects. Genomic DNA was obtained from oral swabs of all participants and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -889 of IL1A and +3954 of IL1B. PCR products were submitted to digestion and analyzed by PAGE to distinguish C and T alleles. RESULTS: There was no significant difference in the genotype or allele distributions of the IL1A -889 C/T and IL1B +3954C/T polymorphisms in patients with TR when compared with controls. However, in a subgroup analysis, the frequency of genotype and allele distributions of IL1A -889 C/T differed significantly between TR patients with and without recurrent episodes. CONCLUSION: This study suggests that the genotypes related with a high production of IL-1a may be associated with the recurrence of TR.

Adrenalectomy enhances endotoxemia-induced hypophagia: higher activation of corticotrophin-releasing-factor and proopiomelanocortin hypothalamic neurons.

Inflammatory and infectious processes evoke neuroendocrine and behavioral changes known as acute-phase response that includes activation of the hypothalamo-pituitary-adrenal (HPA) axis and reduction of food intake. Besides its action as the most important ACTH secretagogue, corticotrophin-releasing factor (CRF), synthesized in the paraventricular nucleus (PVN), is also involved in the control of food intake. Alpha-melanocyte stimulating hormone (alpha-MSH) in the arcuate nucleus also plays a role in the energy homeostasis, possessing anorexigenic effects. To investigate the participation of neuropeptides involved in the regulation of food intake during endotoxemia, we administrated lipopolysaccharide (LPS) in sham-operated and adrenalectomized (ADX) male Wistar rats to evaluate food intake, hormone responses and Fos-CRF and Fos-alpha-MSH immunoreactivity in the PVN and arcuate nucleus, as well as CRF and POMC mRNA expression in these hypothalamic nuclei. In sham-operated rats, treatment with LPS (100 microg/kg) showed lower food intake, higher plasma ACTH and corticosterone levels, as well as an increase in Fos-CRF double labeled neurons and CRF mRNA expression in the PVN, with no changes in Fos-alpha-MSH immunoreactivity and POMC mRNA expression in the arcuate nucleus, compared to saline treated rats. After LPS treatment, ADX rats showed further increase in plasma ACTH levels, marked decrease of food intake, higher Fos-CRF immunoreactive neurons in the PVN and CRF mRNA expression, as well as an increase in Fos-alpha-MSH immunoreactivity and POMC mRNA expression in the arcuate nucleus, compared to sham-operated rats treated with LPS. In conclusion, the present data indicate that the marked hypophagia during endotoxemia following ADX is associated with an increased activation of CRF and POMC neurons in the hypothalamus and an increased mRNA expression of these neuropeptides.

A perturbative approach for enhancing the performance of time series forecasting.

This paper proposes a method to perform time series prediction based on perturbation theory. The approach is based on continuously adjusting an initial forecasting model to asymptotically approximate a desired time series model. First, a predictive model generates an initial forecasting for a time series. Second, a residual time series is calculated as the difference between the original time series and the initial forecasting. If that residual series is not white noise, then it can be used to improve the accuracy of the initial model and a new predictive model is adjusted using residual series. The whole process is repeated until convergence or the residual series becomes white noise. The output of the method is then given by summing up the outputs of all trained predictive models in a perturbative sense. To test the method, an experimental investigation was conducted on six real world time series. A comparison was made with six other methods experimented and ten other results found in the literature. Results show that not only the performance of the initial model is significantly improved but also the proposed method outperforms the other results previously published.

Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia.

Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH.

A joint TEM-HLEM geophysical approach to borehole sitting in deeply weathered granitic terrains.

The accurate location of aquiferous fracture zones in granite beneath a > 50 m thick weathered mantle in semi-arid regions is a major hydrogeological problem. It is expected that the zone of intensive fracturing will be more susceptible to weathering and thus be characterized by the thickest development of saprolite, a good electrically conductive target for deep-probing electromagnetic systems. The single-loop transient electromagnetic (TEM) technique is well known to have the capability for detecting concealed steep mineralized targets in mining environments and can be adapted to this hydrogeological problem. We propose that combining the conventional frequency-domain horizontal-loop electromagnetic (HLEM) and single-loop TEM is an effective practical approach to locating concealed aquiferous fracture zones. In the supporting case studies presented here, we deployed multifrequency HLEM profiling (with 50 m transmitter-receiver separation) and TEM soundings with contiguous 10 or 20 m sided loops along the survey lines in a granitic terrain affected by deep (> 50 m) weathering in northeast Brazil. A somewhat layered structure consisting of resistive hardpan/leached zone, conductive saprolite, and resistive basement is identifiable in the typical TEM depth sounding data. We obtained coincident HLEM and TEM anomalies at all the sites, enabling a relatively straightforward selection of potential drilling positions. Simple resistivity-depth transformation of the TEM data was done for each site, yielding an approximate section from which drilling depths were estimated. All of the boreholes located were successful. Although our results appear to indicate that the single-loop TEM method could be used independently for borehole sitting in deeply weathered granitic terrains and that the weathering profile over granite can be mapped using TEM depth soundings of appropriate observational bandwidth, we recommend a joint electromagnetic approach for optimal well sitting.

Surgical staff resource management of the operating room.

Physician involvement in the resource decision-making process has become an increasingly important objective for administrations and boards. The clinical program budget approach was initiated in the operating room as a test case, combining elements of education, peer review and economic incentives. This trial was successful, resulting in greater awareness of costs as well as budget changes. The Victoria Hospital Corporation experience supports the future viability of clinical program budgeting.

Interleukin-6 gene polymorphism (-174 G/C) is associated with toxoplasmic retinochoroiditis.

PURPOSE: Experimental data have demonstrated a relevant role for IL-6 in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate the possible association between the IL-6 gene polymorphism at position -174 and toxoplasmic retinochoroiditis (TR) in humans. METHODS: Ninety-seven patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, 83 healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -174 of IL-6 (-174G/C). PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish allele G and C of the IL-6 gene, allowing the detection of the polymorphism and determination of genotypes. RESULTS: There was a significant difference in the genotype (χ(2) = 12.9, p = 0.001) and allele (χ(2) = 6.62, p = 0.01) distribution between TR patients and control subjects. In a subgroup analysis, there was no significant difference in genotypes and allele frequencies regarding TR recurrence. CONCLUSIONS: This study suggests that the genotypes related with a lower production of IL-6 may be associated with the occurrence of TR.

Functional IL-10 gene polymorphism is associated with Chagas disease cardiomyopathy.

This study was designed to determine whether the functional IL-10 gene polymorphism -1082G/A is associated with the development of cardiomyopathy in individuals infected with Trypanosoma cruzi and whether interleukin (IL)-10 expression can be correlated with patients' cardiac function. Our results demonstrated that the polymorphic allele, which correlates with lower expression of IL-10, was associated with the development of Chagas disease cardiomyopathy. Accordingly, correlative analysis showed that low IL-10 expression was associated with worse cardiac function, as determined by left-ventricular ejection fraction values. Therefore, the IL-10 gene polymorphism and IL-10 expression are important in determining susceptibility to chagasic cardiomyopathy.

Downregulation of melanocortin-4 receptor during refeeding and its modulation by adrenalectomy in rats.

Melanocortin system and corticotropin releasing hormone (CRH) are implicated in the control of feeding behavior. Besides its anorexigenic effect on food intake, CRH is one of the most important regulators of hypothalamic-pituitary-adrenal (HPA) axis activity. Therefore, there could be an interplay between HPA axis activity and melanocortin system. We investigated the expression of melanocortin-4 receptor (MC4-R) mRNA in the hypothalamus of rats after 14 days of food restriction or after a fasting-refeeding regimen, in sham or adrenalectomized rats. Male Wistar rats were subjected to free access to food or food ingestion restricted for 2 h a day (8-10 AM) during 14 d, when plasma corticosterone, ACTH, insulin, leptin concentrations, and MC4-R mRNA expression were determined before and after refeeding. Another set of rats was fasted for 48 h, followed by refeeding during 2 or 4 h on the seventh day after adrenalectomy (ADX) or sham surgery. On the day of the experiment, rats were anesthetized and perfused and the brain processed for MC4-R mRNA by in situ hybridization. Long-term reduction of food intake, either secondary to food restriction or adrenalectomy, reduced body weight gain and also leptin and insulin plasma concentrations. Food ingestion reduced MC4-R expression in the paraventricular nucleus in naive rats subjected to food restriction and also in sham rats fasted for 48 h. However, after ADX, MC4-R expression was not changed by refeeding. In conclusion, the present data indicate that MC4-R expression is downregulated by food ingestion and this response could be modulated by glucocorticoid withdrawal.

The effect of adrenalectomy on Fos expression in vasopressinergic and oxytocinergic neurons in response to stress in the rat.

This study evaluated the responses of vasopressin (AVP) and oxytocin (OT) neurons to alterations in hypothalamo-pituitary axis activity by adrenalectomy (ADX) or after restraint stress compared with basal conditions. Wistar male rats were perfuse-fixed by cardiac perfusion under anesthesia 3 h, 1, 3 and 14 days after ADX or Sham surgery. Coronal hypothalamic sections were used for evaluation of Fos, AVP and OT expression by immunohistochemistry. Under basal conditions and after stress, Fos-AVP double labeling showed no difference in the magnocellular subdivisions of the paraventricular nuclei (PVN) or in the supraoptic nuclei (SON), suggesting that the magnocellular AVP system is unlikely to contribute to ACTH secretion after restraint in both Sham and ADX rats. Fos-AVP double labeling in the parvocellular medial paraventricular nucleus (PaMP) in ADX groups was increased after 3 h in basal conditions, and in all periods after restraint stress. There were no differences between Sham and ADX groups in Fos-OT double labeling in any subdivision of the PVN; however, in the SON, the number of Fos-OT double labeled cells was increased at all time-points after stress in the ADX group. Fos expression was increased in the PaMP after 3 h and after restraint stress in the Sham and ADX groups, especially in the ADX group. In conclusion, Fos expression in different cell populations of the PVN can be differentially regulated by short- and long-term absence of glucocorticoid negative feedback and also by stress-related excitatory and/or inhibitory neural inputs. The Fos-AVP double labeling findings in the PaMP also indicate a minor participation of these vasopressinergic neurons in the regulation of the HPA axis after ADX.

The interaction of plasma renin activity and plasma atrial natriuretic peptide in 21-hydroxylase deficiency patients.

Plasma renin activity (PRA) determination is the main index used to evaluate the mineralocorticoid control in 21-hydroxylase deficiency (21-OHD). PRA values within or at the upper limit of the age-appropriate range, or values <5 or 10 ng/ml/h have been regarded as adequate control. Atrial natriuretic peptide (ANP) has opposite actions to those of angiotensin II/aldosterone, and could help to understand the hydrosaline homeostasis in 21-OHD. We studied the interaction between PRA and ANP levels in 10 controls and 26 patients with 21-OHD under corticoid treatment. Patients were divided into two groups according to PRA levels, < or > or = 5 ng/ml/h, irrespective of the clinical form of 21-OHD. Blood samples for determination of PRA and ANP levels were taken after 30 min in the sitting position (basal), after 30 min in the recumbent position and after 15 min of 20 degrees head-down tilting. ANP levels (pg/ml) in the basal, supine and after head-down tilting position were 25.9 +/- 1.6, 42.7 +/- 7.4 and 54.3 +/- 5.5 in controls; 28.5 +/- 2.1, 38.3 +/- 2.1 and 48.8 +/- 4.1 in the group with PRA levels <5 ng/ml/h, and 20.9 +/- 1.9, 26.6 +/- 2.5 and 34.6 +/- 3.1 in the group with PRA levels > or = 5 ng/ml/h, respectively. Basal and after head-down tilting ANP plasma levels were similar between the controls and the group with PRA levels <5 ng/ml/h. However, the group of patients with PRA levels > or = 5 ng/ml/h showed lower basal and stimulated ANP levels compared to the control group (p<0.05). The decreased plasma ANP levels in the basal condition and after head-down tilting indicate a chronic contraction of the extracellular volume in 21-OHD patients with increased PRA levels. Therefore, mineralocorticoid deficiency is counteracted by decreased ANP secretion in order to preserve fluid and electrolyte homeostasis.

Potential of the Executive Order Increasing the Participation of Asian Americans and Pacific Islanders in Federal Programs.

OBJECTIVES. This study evaluated the effectiveness of a program designed to reduce primary care treatment barriers for Asian Americans and Pacific Islanders (AAPIs). Interpreters, home health visits, prevention education, cultural sensitivity trainings, and an AAPI phone line were provided to increase the utilization of primary care services at a rural community health center. METHODS. The number of primary care patients and infant immunization rates were measured from 1993& shy;1996. Emergency room visits were measured to assess the impact of primary care increases upon reducing inappropriate emergency room visits. Baseline frequencies and data from other ethnic populations were used as control measures. RESULTS. AAPI primary care patients increased by 87 percent, compared to a total population increases of less than 8 percent. Timely immunization rates for infants rose from 36 percent to 93 percent. Emergency room visits declined by 20 percent. CONCLUSIONS. Treatment barriers for primary care may be reduced for AAPIs if appropriate cultural considerations are addressed. Support for a link between primary care interventions and reduced emergency room utilization is suggested.

Dietetic supplementation with branched chain amino acids attenuates the severity of streptozotocin-induced diabetes in rats.

Previous studies showed that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet, that have markedly elevated plasma concentrations of valine, leucine and isoleucine. In order to test the role of these branched chain amino acids (BCAA) in the beneficial effects of the high-protein diets, rats adapted (15 days) either to a balanced synthetic diet, or to the same diet supplemented with BCAA were injected with streptozotocin (STZ) (40 mg/kg body weight) and maintained on the same diets after drug injection. Rats previously fed the BCAA enriched diet showed a partial but significant reduction in the severity of diabetes, as indicated by higher rates of body weight gain, lower food and water intake, lower excretion of glucose and higher serum insulin levels. Rats previously fed the control diet for 14 days, but transferred to the BCAA diet 3 days after STZ injection, also showed reduced severity of diabetes, as indicated by rates of body weight gain, water and food ingestion, glucose and insulin levels. The data suggest that the increased supply of BCAA is responsible, at least in part, for the previously reported beneficial effects of high-protein diets in rats with STZ-induced diabetes.

Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia

Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76 percent of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19 percent), V281L (18 percent), and IVS2,A/C>G,-12 (15 percent). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38 percent), in the SV form it was I172N (53 percent), and in the NC form it was V281L (57.7 percent). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH