Gender differences and multiple determinants of perceived physical and mental health in Italy.

Background: Perceived health is largely dependent on multiple socio-demographic and behavioral lifestyles and healthcare related factors. This could be accentuated when gender is taken into account. The aim of this study is to explore gender-related differences in multiple socio-demographic and behavioral lifestyles and healthcare related factors associated with individual health status and to identify those responsible for changes in perceived physical and mental health among men and women in Italy. Study design: We conducted a cross-sectional retrospective study to investigate the association between multiple socio-demographic and behavioral lifestyles and healthcare related factors and individual health status of 99,479 adults in Italy, using data and information obtained from a nationwide survey. Methods: To identify the factors that correlate with the perceived physical and mental health status between males and females, we employed a censored regression analysis, a Tobit model, stratifying the analysis by gender. Results: Socio-demographic and behavioral lifestyles factors differently impact on males and females and this impact is stronger on perceived physical than mental health. The perceived physical and mental health status resulted better for men than for women. The integrated analysis of gender differences in socio-demographic and behavioral lifestyles and determinants of health revealed important inequalities, mainly related to citizenship and educational level, among the socio-demographic factors, and smoking habit and obesity, among the behavioral lifestyle factors. Conclusions: Gender imbalances mainly fall into inequality in social inclusion, educational level, and healthy lifestyle. This demonstrates how gender differences are still abundantly present in the modern Italian society. Such information should be taken into consideration by policy makers when interventions to improve the health and quality of life of the population are planned or evaluated.

Axial and rotational alignment of lower limb in a Caucasian aged non-arthritic cohort.

BACKGROUND: The alignment of human lower limb has been an area of ongoing study for decades. The purpose of this study was to analyze the axial and rotational alignment from hip to ankle in a Caucasian aged non-arthritic cohort. METHODS: A non-arthritic cohort of aged patients was retrospectively analyzed by computer tomography. Anatomical-mechanical angle of femur (AMA), femur inclination (FI), femoral anteversion (FA), posterior condylar angle (PCA), proximal tibial torsion (TEAs-PTC and TEAs-PTT) and tibial fibular torsion (PTC-TFA) were measured. RESULTS: The median age of the patients was 76 years (range 67 to 91 years). Regarding axial alignment, the AMA was 5 (2.94; 6.80). No significance differences were reported by side and age. AMA was significantly lower in men. The FI was 125.3 (120.0; 134.8) with no differences in terms of side, age or gender. Regarding torsion alignment, the median values of FA, PTC-TFA and TEAs-PTT were, respectively, 16.8, 28.5 and - 1.4. No differences were reported by age. Right tibia was externally rotated by 1.5 degrees as compared to the left side (P 0.035). CONCLUSION: The broad variability of the parameters analyzed highlights the necessity for a more anatomical and individualized approach during surgery of lower limb. The present study offers the fundament to understand and treat lower limb deformities. Hence, these data can constitute the normal reference values useful to investigate lower limb malalignment. Moreover, it helps to assess the possible changes of axial and rotational alignment in idiopathic OA of lower limb. LEVEL OF EVIDENCE III: Retrospective cohort study.

Characterization of the physical, microbiological, and chemical properties of sonicated raw bovine milk.

Innovative processing technologies, such as ultrasonication, can change the properties of milk, allowing for the improvement or development of dairy foods. Yet taking bench-scale equipment to pilot plant scale has been challenging. Raw milk, standardized to 3% fat and warmed to inlet temperatures of 42 or 54°C, was exposed to continuous, high-intensity, low-frequency ultrasonication (16/20 kHz, 1.36 kW/pass) at flow rates of 0.15, 0.30, and 0.45 L/min that resulted in resident times within the reaction cell of 6, 3, and 2 min per pass, respectively. Multiple passes (3, 5, and 7, respectively) were required to obtain a total exposure time of 14 to 18 min. Evaluation of fat droplet sizes, enzyme coagulation properties, and microstructure of milk and milk gels, as well as determining compositional and lipid properties, were conducted to determine the potential of the ultrasound system to effectively modify milk. Laser scanning particle sizing and confocal microscopy showed that the largest droplets (2.26 ± 0.13 µm) found in raw milk were selectively reduced in size with a concomitant increase in the number of submicron droplets (0.37 ± 0.06 µm), which occurred sooner when exposed to shorter bursts of ultrasonication (0.45 L/min flow rates) and at an inlet temperature of 54°C. Ultrasound processing with milk entering at 42°C resulted in faster gelling times and firmer curds at 30 min; however, extended processing at inlet temperature of 54°C reduced curd firmness and lengthened coagulation time. This showed that ultrasonication altered protein-protein and protein-lipid interactions, thus the strength of the enzyme-set curds. Scanning electron microscopy revealed a denser curd matrix with less continuous and more irregular shaped and clustered strands, whereas transmission electron microscopy showed submicron lipid droplets embedded within the protein strands of the curd matrix. Processing at inlet temperature of 54°C with flow rates of 0.30 and 0.45 L/min also reduced the total aerobic bacterial count by more than 1 log cfu/mL, and the number of psychrophiles below the limit of detection (10 cfu/mL) for this study. Ultrasonication exposures of 14 to 18 min had minimal effect on the milk composition, fatty acid profiles, and lipid heat capacity and enthalpy. The findings show that this continuous ultrasound system, which is conducive to commercial scale-up, modifies the physical and functional properties of milk under the parameters used in this study and has potential use in dairy processing.

The effects of microfluidization on the physical, microbial, chemical, and coagulation properties of milk.

This work examines the use of mild heat treatments in conjunction with 2-pass microfluidization to generate cheese milk for potential use in soft cheeses, such as Queso Fresco. Raw, thermized, and high temperature, short time pasteurized milk samples, standardized to the 3% (wt/wt) fat content used in cheesemaking, were processed at 4 inlet temperature and pressure conditions: 42°C/75 MPa, 42°C/125 MPa, 54°C/125 MPa, and 54°C/170 MPa. Processing-induced changes in the physical, chemical, and microbial properties resulting from the intense pressure, shear, and cavitation that milk experiences as it is microfluidized were compared with nonmicrofluidized controls. A pressure-dependent increase in exit temperature was observed for all microfluidized samples, with inactivation of alkaline phosphatase in raw and thermized samples at 125 and 170 MPa. Microfluidization of all samples under the 4 inlet temperature and processing pressure conditions resulted in a stable emulsion of fat droplets ranging from 0.390 to 0.501 µm, compared with 7.921 (control) and 4.127 (homogenized control) µm. Confocal imaging showed coalescence of scattered fat agglomerates 1 to 3 µm in size during the first 24 h. We found no changes in fat, lactose, ash content or pH, indicating the major components of milk remained unaffected by microfluidization. However, the apparent protein content was reduced from 3.1 to 2.2%, likely a result of near infrared spectroscopy improperly identifying the micellar fragments embedded into the fat droplets. Microbiology results indicated a decrease in mesophilic aerobic and psychrophilic milk microflora with increasing temperature and pressure, suggesting that microfluidization may eliminate bacteria. The viscosities of milk samples were similar but tended to be higher after treatment at 54°C and 125 or 170 MPa. These samples exhibited the longest coagulation times and the weakest gel firmness, indicating that formation of the casein matrix, a critical step in the production of cheese, was affected. Low temperature and pressure (42°C/75 MPa) exhibited similar coagulation properties to controls. The results suggest that microfluidization at lower pressures may be used to manufacture high-moisture cheese with altered texture whereas higher pressures may result in novel dairy ingredients.

Reversal of MYB-dependent suppression of MAFB expression overrides leukaemia phenotype in MLL-rearranged AML.

The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Clustering spatio-temporal series of confirmed COVID-19 deaths in Europe.

The impact of the COVID-19 pandemic varied significantly across different countries, with important consequences in the definition of control and response strategies. In this work, to investigate the heterogeneity of this crisis, we analyse the spatial patterns of deaths attributed to COVID-19 in several European countries. To this end, we propose a Bayesian nonparametric approach, based on mixture of Gaussian processes coupled with Dirichlet process, to group the COVID-19 mortality curves. The model provides a flexible framework for the analysis of time series data, allowing the inclusion in the clustering procedure of different features of the series, such as spatial correlations, time varying parameters and measurement errors. We evaluate the proposed methodology on the death counts recorded at NUTS-2 regional level for several European countries in the period from March 2020 to February 2021.

MR-guided vacuum-assisted breast biopsy in the management of incidental enhancing lesions detected by breast MR imaging.

PURPOSE: The objective of this study was to determine the clinical value and accuracy of magnetic resonance (MR)-guided vacuum-assisted breast biopsy (VAB). MATERIALS AND METHODS: We retrospectively analysed 106 incidental breast lesions detected on MR imaging in 98 patients. Patients with nonpalpable suspicious lesions that were only MR visible were referred for MR-VAB performed with a 10-gauge needle. All patients with a VAB diagnosis of infiltrating carcinoma, carcinoma in situ or atypical epithelial hyperplasia were referred for surgery. Histopathology of the surgical specimen was considered the reference standard. RESULTS: MR-guided VAB was attempted in 29/106 lesions (27%); in 2/29 patients, the procedure could not be performed owing to failure to visualise the lesion. Lesions with clearly malignant features and borderline lesions (atypical ductal hyperplasias) were identified in 12 cases (44%) and benign entities in 15 (56%). Seven of 12 (58%) malignant lesions were <10 mm. Among the 27 successful MR-VAB procedures, VAB yielded one false-negative diagnosis (4%) and underestimation (4%). MR-guided VAB sensitivity and specificity were 92% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 93%. CONCLUSIONS: The results of this study indicate that MR-guided VAB offers good accuracy in characterising nonpalpable breast lesions visible on MR imaging alone. Small lesion size (<1 cm) did not prove to be a limitation for the success of the procedure.

Multifocal, multicentric and contralateral breast cancers: breast MR imaging in the preoperative evaluation of patients with newly diagnosed breast cancer.

PURPOSE: This study was done to verify the usefulness of preoperative breast magnetic resonance (MR) imaging in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: A retrospective analysis of 291 patients with invasive breast cancer newly diagnosed with conventional breast imaging (mammography and ultrasound) was performed. All patients underwent MR imaging prior to surgery. The MR imaging detection rate of additional malignant cancers occult to mammography and ultrasound was calculated. Data were analysed with Fisher's exact test (p<0.05) according to the following parameters: histopathological features of the index tumour (histological type and size) and mammographic density [according to the Breast Imaging Reporting and Data System (BI-RADS) classification from 1 fatty to 4 dense). The gold standard was the histological examination on the surgical specimen. RESULTS: MR imaging identified 40 mammographically and sonographically occult malignant lesions other than the index cancer in 27/291 patients (9%). These additional cancers were located in the same quadrant as the index cancer in 13 women (4%), in a different quadrant in 12 (4%) and in the contralateral breast in the remaining two (1%). The cancer detection rate in the subgroup of index cancers with lobular histological type was 25%, significantly higher (p=0.03) than the detection rate of 11% recorded in the subgroup of ductal cancers. The cancer detection rate in the subgroup of index cancers >2 cm was 27%, significantly higher (p=0.001) than the rate of 8% found in the subgroup of index cancers <2 cm. Mammographic density was not correlated (p=0.48) with MR detection of additional cancer, with 14% of additional malignancies being detected in both dense and fatty breasts. CONCLUSIONS: In patients with newly diagnosed invasive breast cancer, preoperative MR imaging is useful for detecting additional synchronous malignancies that are not detected on conventional breast imaging. The cancer detection rate is 9%. The use of preoperative MR imaging as an adjunct to conventional breast imaging in women with an infiltrating lobular index cancer and an index cancer >2 cm is especially beneficial.

Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man.

To compare glutamine and alanine as gluconeogenic precursors, we simultaneously measured their systemic turnovers, clearances, and incorporation into plasma glucose, their skeletal muscle uptake and release, and the proportion of their appearance in plasma directly due to their release from protein in postabsorptive normal volunteers. We infused the volunteers with [U-14C] glutamine, [3-13C] alanine, [2H5] phenylalanine, and [6-3H] glucose to isotopic steady state and used the forearm balance technique. We found that glutamine appearance in plasma exceeded that of alanine (5.76 +/- 0.26 vs. 4.40 +/- 0.33 mumol.kg-1.min-1, P < 0.001), while alanine clearance exceeded glutamine clearance (14.7 +/- 1.3 vs. 9.3 +/- 0.8 ml.kg-1.min-1, P < 0.001). Glutamine appearance in plasma directly due to its release from protein was more than double that of alanine (2.45 +/- 0.25 vs. 1.16 +/- 0.12 mumol.kg-1.min-1, P < 0.001). Although overall carbon transfer to glucose from glutamine and alanine was comparable (3.53 +/- 0.24 vs 3.47 +/- 0.32 atoms.kg-1.min-1), nearly twice as much glucose carbon came from protein derived glutamine than alanine (1.48 +/- 0.15 vs 0.88 +/- 0.09 atoms.kg-1.min-1, P < 0.01). Finally, forearm muscle released more glutamine than alanine (0.88 +/- 0.05 vs 0.48 +/- 0.05 mumol.100 ml-1.min-1, P < 0.01). We conclude that in postabsorptive humans glutamine is quantitatively more important than alanine for transporting protein-derived carbon through plasma and adding these carbons to the glucose pool.

Beneficial effects of carotenoid-producing cells of Bacillus indicus HU16 in a rat model of diet-induced metabolic syndrome.

A well-established rat model of diet-induced metabolic syndrome was used to evaluate the effects of the oral administration of spores or cells of HU16, a carotenoid-producing strain of Bacillus indicus. Symptoms of metabolic syndrome were induced in 90-days old, male Sprague-Dawley rats maintained for eight weeks on a high-fat diet, as previously reported. Parallel groups of animals under the same diet regimen also received a daily dose of 1×1010 cells or spores of B. indicus HU16. Cells of strain HU16 were able to reduce symptoms of metabolic syndrome, plasma markers of inflammation and oxidative markers in plasma and liver to levels similar to those observed in rats under a standard diet. HU16 cells did not affect obesity markers or the accumulation of triglycerides in the liver of treated animals. Denaturing gradient gel electrophoresis analysis showed that the oral administration of HU16 cells did not significantly affect the gut microbiota of high fat-fed rats, suggesting that the observed beneficial effects are not due to a reshaping of the gut microbiota but rather to metabolites produced by HU16 cells.

Glutamine and alanine metabolism in NIDDM.

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.

Circadian blood pressure changes and myocardial ischemia in hypertensive patients with coronary artery disease.

OBJECTIVES: We sought to evaluate whether different circadian blood pressure (BP) changes could influence the occurrence of ischemic episodes in untreated and treated hypertensive patients with stable coronary artery disease (CAD). BACKGROUND: In hypertensive patients with CAD the occurrence of myocardial ischemia could be influenced by either high or low BP values. Ambulatory monitoring has shown that circadian BP profile is not uniform in hypertensive patients. METHODS: Twenty-one patients with a nighttime BP fall < 10% ("nondippers"), 35 with a nighttime BP fall between > 10% and < 20% ("dippers") and 14 with a nighttime BP fall > 20% ("overdippers") with CAD underwent simultaneous ambulatory BP and electrocardiographic monitoring before and during drug therapy with nitrates and atenolol or verapamil in a prospective, randomized, open, blinded end point design. RESULTS: Daytime BP was not significantly different among the groups both before and during therapy. Nighttime BP was different by definition. Treatment significantly reduced BP values in each group (p < 0.05). Daytime ischemic episodes did not differ among the groups either before or during therapy. Drug therapy significantly reduced daytime ischemia (p < 0.05). In untreated patients, nighttime ischemia was more frequent in nondippers than in dippers and overdippers (p < 0.05). Drug therapy significantly reduced nocturnal ischemia in nondippers (p < 0.05), had no significant effect in dippers and significantly increased nighttime ischemia in overdippers (p < 0.05). During treatment, nighttime ischemia was more frequent in overdippers than in dippers and nondippers (p < 0.05). The same results were achieved when ischemic episodes were defined with more restrictive criteria (ST segment depression > or = 2 mm). CONCLUSIONS: Circadian BP changes can influence the occurrence of myocardial ischemia in untreated and treated hypertensive patients with CAD. Nocturnal ischemia was found to be more frequent in nondippers among untreated patients and in overdippers among treated patients, potentially suggesting different therapeutic approaches based on circadian BP profile.

Allogeneic hemopoietic stem cell transplantation in solid tumors.

The existence of a graft versus tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation is well established as a critical component for the success of the procedure in several hematologic malignancies. Although it has been suggested that a GVT effect might also be generated in patients affected by refractory solid tumors, the morbidity of conventional allogeneic hematopoietic stem cell transplantation has limited its investigation in these diseases. Recently introduced allogeneic nonmyeloablative regimens have greatly decreased morbidity and mortality related to transplants which retain a powerful GVT. On this basis, it has become possible to explore the existence of alloreactivity toward solid tumors. The present article reviews the early clinical results of this novel immunotherapeutic approach for solid tumors.

Low-density lipoprotein oxidation and vitamins E and C in sustained and white-coat hypertension.

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in white-coat hypertension in comparison with sustained hypertension and normotension. We selected 21 sustained hypertensive subjects, 21 white-coat hypertensive subjects, and 21 normotensive subjects matched for gender, age, and body mass index. White-coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <139/90 (subjects were also reclassified using 134/90 and 135/85 mm Hg as cutoff points for daytime blood pressure). Blood samples were drawn for lipid profile determination, assessment of fluorescent products of lipid peroxidation in native LDL, evaluation of susceptibility to LDL oxidation in vitro (lag phase and propagation rate), and determination of LDL vitamin E and plasma vitamins E and C contents. Compared with sustained hypertensive subjects, white-coat hypertensives had significantly lower fluorescent products of lipid peroxidation (15.4+/-3.4 versus 10.2+/-3 units of relative fluorescence/mg LDL protein, P<.05), longer lag phase (54+/-10 versus 88+/-10 minutes, P<.05), lower propagation rate (8.2+/-2.5 versus 5.95+/-2.1 nmol diene/min per mg LDL cholesterol, P<.05), higher LDL vitamin E content (8.3+/-1.1 versus 10.1+/-1.8 nmol/mg LDL cholesterol, P<.05), and plasma vitamin C content (40+/-13 versus 57+9 micromol/L, P<. 05). No significant difference was observed between white-coat hypertensive and normotensive subjects. The results did not change after reclassification of subjects. Our data show that white-coat hypertensive subjects do not show an enhanced propensity to LDL oxidation or reduction in antioxidant vitamins. Given the role of LDL oxidation in the development of atherosclerosis and that of vitamin E and C in protecting against it, these findings suggest that white-coat hypertension per se carries a low atherogenic risk.

Behavior of small thyroid cancers found by screening radiation-exposed individuals.

Thyroid cancers detected by screening irradiated individuals are often small and of uncertain clinical significance. We retrospectively analyzed the effect of screening in a cohort of 4296 individuals exposed to radiation as children in the 1940s and 1950s and followed by us from 1974 until the present. We compared the thyroid cancers diagnosed before 1974 (122 cases, routine care) with the cancers found in subjects screened by us after 1974 (172 cases, screened), using cancer recurrence as the end point. Screening included a thyroid scan or, more recently, thyroid ultrasound. As expected, many of the cancers found by screening were very small (52% were <10 mm), but the range of tumor sizes overlapped those found by routine care. The recurrence rate was significantly lower in the cases found by screening, but when the comparison was limited to cancers 10 mm or larger, no difference in the recurrence rates was seen. This would suggest that the lower recurrence rate observed for small thyroid cancers detected at screening was due to earlier diagnosis rather than more effective treatment. By univariate analysis, four factors were associated with an increased risk of recurrence of small (<10 mm) thyroid cancers: short latency (i.e. a shorter time interval between the radiation exposure and the first thyroid surgery), lymph node metastases present at diagnosis, multifocal cancers, and higher radiation dose. In a multivariate analysis combining the four risk factors, only short latency was significant. As thyroid cancers that escape detection by routine means should be diagnosed at screening, and both large and small thyroid cancers have the potential to recur, screening may be of value, but only if groups with a sufficiently high prevalence of thyroid cancer can be identified to offset the adverse effects of unnecessary treatment due to false positive results.

Twenty-four-hour autonomic nervous function in sustained and "white coat" hypertension.

BACKGROUND: It is unknown whether "white coat" hypertension, also known as isolated clinic hypertension, shares similarities in pathophysiologic background with sustained hypertension. Therefore we evaluated 24-hour autonomic nervous function in sustained and white coat hypertension. METHODS: We selected 12 patients with sustained hypertension (clinic blood pressure >/=140/90 mm Hg and daytime blood pressure >135/85 mm Hg) and 12 patients with white coat hypertension (clinic blood pressure >/=140/90 mm Hg and daytime blood pressure <135/85 mm Hg) from patients undergoing ambulatory blood pressure monitoring and 12 normotensives for study inclusion. Groups were matched for age, sex, and body mass index and had similar dietary pattern and occupational status (civil servants with sedentary jobs). Subjects underwent noninvasive 24-hour monitoring of blood pressure, R-R interval of the electrocardiogram, body position, activity rate, and ambient temperature. Power spectral analysis of R-R intervals was performed with an autoregressive model to obtain the low-frequency component, the high-frequency component, and their ratio. Subjects also collected 24-hour urine samples for examination of norepinephrine and epinephrine excretion by high-performance liquid chromatography. RESULTS: Work and sleep time, body position, ambient temperature, and activity were not different among the groups. Daytime, nighttime, and 24-hour low-frequency/high-frequency ratios were significantly higher in patients with sustained hypertension than in patients with white coat hypertension (3.4 +/- 0.45 vs 2.65 +/- 0.45, 2.35 +/- 0.60 vs 1. 82 +/- 0.45, and 3.04 +/- 0.45 vs 2.4 +/- 0.35, respectively, P <. 05). Urinary norepinephrine excretion (53 +/- 12 microg vs 29.5 +/- 6 microg; P <.05) and vanillylmandelic acid excretion (4.45 +/- 0.6 mg vs 3.1 +/- 0.55 mg; P <.05) during the 24 hours were significantly higher in patients with sustained hypertension than in those with white coat hypertension. There was no difference between those with white coat hypertension and normotensives concerning the aforementioned parameters. CONCLUSIONS: Our findings indicate whole-day sympathetic overactivity in sustained hypertension but not in white coat hypertension, suggesting that these conditions show some differences in pathophysiologic background.

Mosquito infectivity is directly related to the proportion of repetitive DNA in Plasmodium berghei.

A strain of Plasmodium berghei (NK 65) was followed during syringe transmission in mice for over 120 passages after the last complete cycle, while the following parameters were monitored: (a) capacity to infect mosquitoes, inducing oocyst formation; (b) presence in the peripheral blood of morphologically identifiable gametocytes; (c) presence of a repetitive component in the DNA extracted from intraerythrocytic population. The suggestion of a possible role of this component in gametogenesis came from an earlier work (Dore, E., Birago, C., Frontali, C. and Battaglia, P.A. (1980) Mol. Biochem. Parasitol. 1, 199-208). Present results confirm the correlation between proportion of repetitive DNA and infectivity towards mosquitoes with a correlation coefficient r = 0.92-0.07+0.04. A parallel decrease of the two quantities is observed in the course of syringe transmission. A limited number of cloned lines, derived from strain NK 65 at different times during syringe transmission, shared the infectivity properties of the parent strain at the moment of cloning, thus confirming that in the infective stage single asexual parasites from the schizogonic cycle are able to originate the whole cycle. The above arguments and results suggest that differentiation into active gametocytes involves amplification of a portion of the genome.

White-coat resistant hypertension.

The aim of this study was to evaluate whether sustained hypertensives with high clinic blood pressure, despite multiple drug treatment, show a true resistant hypertension or a "white-coat effect," and whether the pretreatment white-coat effect is maintained despite pharmacological therapy. The occurrence of resistant hypertension was determined in 250 consecutive essential hypertensives who had had an ambulatory blood pressure monitoring before treatment assignment. Twenty-seven of 250 hypertensives with persistently high clinic blood pressure despite 3 months of adequate pharmacological therapy underwent further ambulatory blood pressure monitoring. Using our internal standards, seven patients had a true resistant hypertension whereas 20 subjects showed a large white-coat effect (white-coat resistant hypertension), ie, high clinic blood pressure (> 140/90) but "normal" ambulatory daytime (< 139/90 mm Hg) and 24 h (135/85 mm Hg) blood pressure. Using other cutoff points for ambulatory blood pressure, 134/90 and 135/85 mm Hg for daytime blood pressure, 10 and 13 patients, respectively, were reclassified as true resistant hypertensives and 17 and 14, respectively, were white-coat resistant hypertensives. Interestingly, in white-coat resistant hypertensives the large differences between clinic and ambulatory daytime blood pressure (white-coat effect), recorded before treatment assignment, were not affected by drugs and remained constant over time. Left ventricular mass index in white-coat resistant hypertensives was significantly lower than in truly resistant hypertensives, suggesting that prognosis could differ between these groups. In this study, using either our internal standards or some other cutoffs reported in the literature, the white-coat phenomenon was an important cause of resistant hypertension. The use of ambulatory blood pressure monitoring in these patients may avoid misdiagnosis of resistant hypertension, unnecessary overtreatment, and expensive procedures to look for possible secondary hypertension.

Blunted nocturnal fall in blood pressure and oxidative stress in men and women with essential hypertension.

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in dipper (nocturnal blood pressure fall > 10%) and nondipper (nocturnal blood pressure fall < 10%) hypertensives. We studied 40 dippers and 28 nondippers balanced for gender, age, and body mass index. Blood samples were drawn for lipid profile determination, assessment of thiobarbituric acid-reactive substances, and fluorescent products of lipid peroxidation in native low-density lipoprotein, evaluation of susceptibility to low-density lipoprotein oxidation in vitro (lag phase and propagation rate), and determination of low-density lipoprotein vitamin E and plasma vitamins E and C contents. Compared with dippers, nondippers had significantly higher thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation (0.63 +/- 0.1 v 0.77 +/- 0.08 nmol malondialdehyde/mg low-density lipoprotein protein, and 14.5 +/- 6 v 17.9 +/- 4 units of relative fluorescence/mg low-density lipoprotein protein, respectively, both P < .05), shorter lag phase (56 +/- 13 v 49 +/- 9 min, P < .05), and lower plasma vitamin C content (42 +/- 9 v 35 +/- 10 micromol/L, P < .05). When gender was taken into account, differences were not significant between dipper and nondipper men, whereas, compared with dipper women, nondipper women showed significantly higher thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation (0.56 +/- 0.1 v 0.77 +/- 0.07 nmol malondialdehyde/mg low-density lipoprotein protein, and 12.5 +/- 4 v 17.5 +/- 4.6 units of relative fluorescence/mg low-density lipoprotein protein, respectively, both P < .05), shorter lag phase (62.5 +/- 11 v 49 +/- 9.5 min, P < .05), and lower plasma vitamin C content (44.9 +/- 10 v 34.7 +/- 10.8 micromol/L, P < .05). Given the role of low-density lipoprotein oxidation in the pathogenesis of atherosclerosis and that of vitamin C in protecting against it, our data suggest that nondippers, especially among women, show higher atherogenic risk than dippers.

Endogenous ouabain and hemodynamic and left ventricular geometric patterns in essential hypertension.

We sought to evaluate the relationships among circulating levels of an endogenous ouabain-like factor (EO) and systemic hemodynamics and left ventricular (LV) geometry in patients with recently diagnosed essential hypertension. We selected 92 never-treated patients with essential hypertension. Blood samples were drawn for estimation of plasma EO (radioimmunoassay) and subjects underwent echocardiographic examination to evaluate LV end-systolic and end-diastolic wall thickness and internal dimensions. LV volumes, stroke volume, cardiac output, total peripheral resistance, LV mass, and relative wall thickness were calculated, and all except the last parameter were indexed by body surface area. LV mass also was indexed by height. On the basis of the values of LV mass index (body surface area or height) and relative wall thickness, subjects were divided into groups with either normal geometry, concentric remodeling, concentric hypertrophy, or eccentric nondilated hypertrophy. In the study population as a whole, circulating EO levels were significantly and directly correlated with mean blood pressure (r = 0.21, P = .048), relative wall thickness (r = 0.34, P = .001), and total peripheral resistance index (r = 0.37, P = .0003). Plasma EO also was significantly and inversely correlated with LV end-diastolic volume index (r = -0.32, P = .002), stroke index (r = -0.34, P = .0009), and cardiac index (r = -0.35, P = .0007). In multiple regression analysis, plasma EO was an independent correlate of total peripheral resistance index, cardiac index, and relative wall thickness. Regardless of the indexation method used for LV mass, plasma EO was higher in patients with concentric remodeling than in those with either normal geometry or concentric hypertrophy. Plasma EO tended to be higher (indexation by body surface area) or was significantly higher (indexation by height) in subjects with concentric remodeling than in those with eccentric nondilated hypertrophy. Patients with concentric remodeling showed the highest total peripheral resistance index and the lowest cardiac index. Our data suggest that EO plays a role in regulating systemic hemodynamics and LV geometry in patients with essential hypertension.