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Wildlife damage to forests has become an increasingly serious problem in recent years, and its impact is exacerbated by ongoing climate change. Rising temperatures, prolonged droughts, uneven precipitation distribution, and other factors affect forest ecosystems, which, in turn, affect cloven-hoofed animal populations, their food preferences, and ultimately, the extent of damage they cause. Based on 133 references, this review article focuses on the relationships between wildlife damage and climate change and presents possible strategies to address this issue in the Czech Republic. Wildlife damage includes not just browsing and fraying in natural and artificial regeneration but also damage to trees from bark stripping and the lesser-known rooting of seedlings. Concerning tree species, browsing is most damaging to silver fir (Abies alba Mill.) and sycamore maple (Acer pseudoplatanus L.). The enticement to wildlife increases as the proportion of the tree species in the stand decreases. Browse damage is more severe at the edge of the stand. Bark stripping and secondary rot cause the most damage to the production quality of Norway spruce (Picea abies [L.] Karst.). Total wildlife damage increases with elevation. Combined with the progress of climate change, game-induced damage significantly restricts close-to-nature forest management practices and limits the use of adaptive measures in response to climate change. In addition, mixed forests with species that attract wildlife and the rapid increase in the number of clearings following bark beetle salvage logging significantly increase game pressure. This is primarily the result of the overpopulation of native and introduced game species and the considerable inconsistency between forest and hunting management practices, with the latter not respecting the principle of ecologically tolerable game damage.

On the one hand, the European beech (Fagus sylvatica L.) is the tree of the future due to ongoing climate changes, on the other hand, there are questions about its expansion and economic use as a replacement for the declining Norway spruce (Picea abies [L.] Karst.). This literature review examines 140 studies summarizing basic research on beech in the context of climate change. As a climax tree species, beech is becoming dominant again in parts of its original range at the middle and higher altitudes of Central Europe, following spruce. It is a shade-loving species that can thrive in various types of mixed forest stands. To cultivate beech, close-to-nature methods, shelterwood, or selection management are optimal. The occurrence of the beech seed year is influenced by factors such as precipitation, temperature, drought, and air pollution. Although beech is generally considered resistant to abiotic and biotic factors, it often needs protection against hoofed game browsing in the earliest stages of development. As climate change progresses, it is essential to cultivate beech in areas rich in precipitation and nutrients where it can thrive even under more extreme conditions. In optimal conditions, beech has shown intensive regeneration in recent years, aggressively displacing other tree species. However, with insufficient precipitation and prolonged periods of drought, beech loses its vigor, production, and ability to compete. For adaptation to climate change, it is recommended to select appropriate beech provenance, promote natural regeneration, and cultivate structurally differentiated stands through positive-selection thinning from above.

Only 1.82% of the Czech forests are covered by the introduced (exotic, non-native) tree species, they represent only a very minor part of the forest area in the Czech Republic. Despite this fact under certain circumstances and locally, they can play an important role in the forest restoration of declined forests. The main non-native tree species used in the Czech Republic are: black locust (Robinia pseudoacacia L.), Douglas-fir (Pseudotsuga menziesii [Mirbel] Franco), grand fir (Abies grandis [Douglas ex D. Don] Lindl.), black walnut (Juglans nigra L.), northern red oak (Quercus rubra L.), and blue spruce (Picea pungens Engelm.). Other tree species are cultivated on very small areas, despite their much larger potential. The aim of the presented review paper is to summarize information on the introduced tree species, available especially from national sources, and give comprehensive information concerning the potential and risk of their use in the conditions of the Czech Republic. The authors mention also other tree species eligible for silviculture under current as well as future climatic circumstances. The current area and silvicultural potential in the climate changing conditions are analysed and summarized.

Tree damage by game browsing is one of the biggest threats to forest ecosystems at the time of climate change and large-scale forest disturbances. The aim of the paper was to determine the effect of browsing by ungulates on the diversity, abundance and species composition of natural regeneration in forest stands dominated by European beech (Fagus sylvatica L.). The research was conducted on 10 permanent research plots in the Krušné hory Mts. in the Czech Republic and Germany. The density of natural regeneration was in the range of 23,300–114,100 recruits ha−1. A higher proportion of silver birch (Betula pendula Roth.) and rowan (Sorbus aucuparia L.) was found in the regeneration compared to the mature stands. A total of 78% of recruits was damaged by browsing. The most frequently damaged tree species were sycamore (Acer pseudoplatanus L.; 98%) and black alder (Alnus glutinosa [L.] Gaertn.; 97%), while Norway spruce (Picea abies [L.] Karst; 31%) and sessile oak (Quercus petraea [Matt.] Liebl.; 50%) were the least affected. Seventy-nine percent of European beech recruits were damaged. The game significantly reduced the height of regeneration by up to 40%, especially by terminal browsing. Browsing also negatively affected the quality and abundance of regeneration. For successful dynamics of species-rich natural forest ecosystems, it is necessary to minimize tree damage by game browsing. These main measures include the reduction of ungulate population levels and the optimization of their age structure and sex ratio, an increase in the number of overwintering enclosures and food fields for game and a change in the political approach to game management with sufficient consideration of forestry interests.

Author(s): H-J Ch'ang; J G Maj; F Paris; H R Xing; J Zhang; J-P Truman; C Cardon-Cardo; A Haimovitz-Friedman; R Kolesnick; Z Fuchs Nat. Med. 11, 484-490 (2005) In Figure [...]

Closure is a problem of defining the convective intensity in a given parameterization. In spite of many years of efforts and progress, it is still considered an overall unresolved problem. The present article reviews this problem from phenomenological perspectives. The variables that are expected to contribute in defining the convective intensity are listed, and their statistical significances identified by observational data analyses are reviewed. A possibility is discussed for identifying a correct closure hypothesis by performing a linear stability analysis of tropical convectively-coupled waves with various different closure hypotheses. Various individual theoretical issues are considered from various different perspectives. Finally, it is emphasized that the dominant physical factors controlling convection differ between the tropics and extra-tropics, as well as between oceanic and land areas. Both observational as well as theoretical analyses, often focused on the tropics, do not necessarily lead to conclusions consistent with our operational experiences focused on midlatitudes. Though we emphasize the importance of the interplays between these observational, theoretical and operational perspectives, we also face challenges for establishing a solid research framework that is universally applicable. [ABSTRACT FROM AUTHOR]

Background: The impact of chronic conditions on the development of disability has not yet been comprehensively studied among the elderly population living in Israel. This study evaluates the prevalence of disability and morbidity among the community-dwelling oldest-old population and examines the association between medical conditions, comorbidity, and disability in basic and instrumental activities of daily living (ADLs, IADLs).Method: The data are based on a national random stratified sample of 1,820 Israeli Jewish individuals 75-94 years old, of whom 1,487 lived in the community.Results: Nineteen percent of the population was disabled in ADLs and 36% in IADLs. Disability rose with age and was higher for women and among individuals of Middle Eastern and North African origin. Stepwise logistic regression indicates that the variables associated with disability in ADLs and IADLs were older age, Middle Eastern or North African origin, living with others, and the following conditions: stroke, hip fracture, diabetes, osteoporosis, anemia, and heart attack. In addition, lower education and suffering from urinary or kidney diseases, respiratory disease, and/or Parkinson's disease were related to disability in ADLs; being a woman and suffering from heart diseases other than heart attack were related to disability in IADLs. Comorbidity was related to increased disability only for individuals with three or more conditions.Conclusions: The identification of medical conditions and sociodemographic variables related to limitations in functioning may serve as a basis for health promotion and disease prevention in elders by attempting to reduce the incidence and disabling consequences of known disabling conditions. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a genetic disease leading to malformations, or tubers, in the cerebral cortex and growth of tumors, most frequently in the brain, heart, kidneys, skin, and lungs. Changes in the brain caused by TSC usually have the biggest negative impact on quality of life. Approximately 85% of individuals with TSC have epilepsy, and TSC-associated neuropsychiatric disorders (TAND) affect nearly all individuals with TSC in some way. TSC Alliance's research strategy is built upon both funding and catalyzing research. Through grants, the organization provides funding directly to researchers through a competitive application process. The organization has also built a set of resources available to researchers worldwide, including a Natural History Database, Biosample Repository, and Preclinical Consortium. These resources catalyze research because they are available to qualified academic or industry researchers around the world, enabling an almost unlimited number of scientists to access data and resources to enable and accelerate research on TSC. This research strategy continues to be shaped by the needs and priorities of the TSC community, working toward a future where everyone affected by TSC can live their fullest lives., Competing Interests: All authors are employees of the TSC Alliance., (© The Author(s), 2024.)

This paper presents the results of an eyetracking study that uses the Visual World Paradigm to determine whether heritage speakers of Polish can use grammatical gender cues to facilitate lexical retrieval of the subsequent noun during real time processing. Previous work has investigated this question for heritage speakers of Spanish with gender cues located on definite articles, which are highly frequent in Spanish; the results are therefore consistent both with a grammatical account, wherein heritage speakers access abstract syntactic gender features during processing, and a probabilistic account, wherein facilitation is due to transition probabilities between frequently co-occurring elements. In Polish, gender cues appear on adjectives, which are optional and infrequent. Results of the present study show that heritage speakers of Polish can use gender on inflected adjectives to fixate on the target noun faster in trials where that gender cue uniquely identifies the target noun. This finding supports a grammatical rather than probabilistic account of the facilitative use of grammatical gender in this population: heritage speakers are able to access abstract syntactic information in real time to aid word recognition in a target-like manner., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fuchs.)

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations., Methods: Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required., Results: Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals., Conclusions: Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Intraosseous (IO)-access plays an alternative route during resuscitation. Our study in preterm and term stillborns was performed to find alternative IO puncture sites beside the recommended proximal tibia., Methods: The cadavers used were legal donations. 20 stillborns (mean: 29.2weeks, IQR 27.1-39.6) were investigated. Spectral-CT were analysed to calculate the diameter and circumferences of: i) proximal humerus ii) distal femur iii) proximal tibia iv) diaphyseal tibial. Contrast medium was applied under video documentation to investigate the drainage into the vascular system., Results: In term newborns, diameter of the cortex of the proximal humeral head is 12.1 ± 1.8 mm, distal end of the femur 11.9 ± 3.4 mm and the proximal tibial bone 12.0 ± 2.4 mm with cross-sectional diameter of 113.5 ± 19.7 mm 2 , 120.6 ± 28.2 mm 2 and 111.6 ± 29.5 mm 2 , respectively. Regarding the preterm groups, there is a strong age-related growth in diameter and cross -sectional size. The diaphyseal area is the smallest in all measured bones with an age-dependent increase and is about half of that of metaphyseal diameters (proximal and distal) and about one third of that of metaphyseal cross sectional areas. The proximal femoral head region has the largest diameter of all measured bones with an egg-shaped formation with an extensive joint capsula. All investigated metaphyseal areas lack a clearly enclosed bone marrow cavity. Infusion of contrast medium into the distal femoral end and the proximal humerus head demonstrate the drainage of contrast medium into the central venous system within seconds., Conclusion: Proximal humeral head and distal femoral end might be alternative IO areas which may lead to further IO puncture sites in neonates., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Intraosseous (IO)-access plays an alternative route during resuscitation. Our study was performed to investigate the successful rate of IO-access in preterm and term stillborns using different devices and techniques., Methods: The cadavers used were legal donations. 16 stillborns, median: 29.2 weeks (IQR 27.2-38.4) were investigated. Two different needles (a: Butterfly needle, 21G, Venofix ® Fa.Braun; b: Arrow ® EZ-IO ® 15G, Teleflex, Dublin, Ireland) were used. Needles were inserted i: manually, using a Butterfly needle; ii: manually, using EZ-IO ® needle or iii: using a battery-powered semi-automatic drill (Arrow ® EZ-IO ® ). Spectral-CT's were performed. The diameter of the corticalis was determined from the CT-images. Successful hit rates with 95% confidence intervals (CI) and odds ratios between the three methods were estimated using a generalised linear mixed model (GLMM)., Results: Estimated success rate was 61.1% (95%CI:39.7%-78.9%) for the Butterfly needle, 43.0% (95%CI:23.4%-65.0%) for hand-twisted EZ-IO ® screwing and 39.7% (95%CI:24.1-57.7%) for the semi-automatic drill (Arrow ® EZ-IO ® ), all referring to an average diameter of the corticalis of 1.2 mm. The odds of a correct position were 2.4 times higher (95%CI:0.8-7.6) when using the Butterfly needle than with the drill. In contrast, the odds of correct positioning when inserting the needle by hand were not significantly different from using the drill (odds ratio 1.1, 95%CI: 0.4-3.3). Neither of these effects nor the diameter of the corticalis with an odds ratio near one were significant in the model. Median diameter of the bone marrow cavity was 4.0 mm [IQR 3.3-4.7]., Conclusion: Intraosseous access for premature and neonatal infants could be best achieved by using a manually twisted Butterfly needle., (Copyright © 2018 Elsevier B.V. All rights reserved.)

PEGylated liposomes have transformed chemotherapeutic use of doxorubicin by reducing its cardiotoxicity; however, it remains unclear whether liposomal doxorubicin is therapeutically superior to free doxorubicin. Here, we demonstrate a novel PEGylated liposome system, named DAFODIL (Doxorubicin And 5-Flurouracil Optimally Delivered In a Liposome) that inarguably offers superior therapeutic efficacies compared to free drug administrations. Delivery of synergistic ratios of this drug pair led to greater than 90% reduction in tumor growth of murine 4T1 mammary carcinoma in vivo. By exploiting synergistic ratios, the effect was achieved at remarkably low doses, far below the maximum tolerable drug doses. Our approach re-invents the use of liposomes for multi-drug delivery by providing a chemotherapy vehicle which can both reduce toxicity and improve therapeutic efficacy. This methodology is made feasible by the extension of the ammonium-sulfate gradient encapsulation method to nucleobase analogues, a liposomal entrapment method once conceived useful only for anthracyclines. Therefore, our strategy can be utilized to efficiently evaluate various chemotherapy combinations in an effort to translate more effective combinations into the clinic., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This paper discusses a common reality in many cases of multilingualism: heritage speakers, or unbalanced bilinguals, simultaneous or sequential, who shifted early in childhood from one language (their heritage language) to their dominant language (the language of their speech community). To demonstrate the relevance of heritage linguistics to the study of linguistic competence more broadly defined, we present a series of case studies on heritage linguistics, documenting some of the deficits and abilities typical of heritage speakers, together with the broader theoretical questions they inform. We consider the reorganization of morphosyntactic feature systems, the reanalysis of atypical argument structure, the attrition of the syntax of relativization, and the simplification of scope interpretations; these phenomena implicate diverging trajectories and outcomes in the development of heritage speakers. The case studies also have practical and methodological implications for the study of multilingualism. We conclude by discussing more general concepts central to linguistic inquiry, in particular, complexity and native speaker competence.

Objectives: This study compares depression levels among lifetime kibbutz members (n = 525) and old-age kibbutz residents (n = 366) with a comparable national sample (n = 412) and assesses the relationship between depression and individual differences related to lifetime in a kibbutz (e.g., health) and those related to current living conditions (e.g., social network)., Methods: The analysis is based on data from the Cross-Sectional and Longitudinal Aging Study conducted in Israel between 1989 and 1992 and the follow-up during 1993 and 1994., Results: The findings indicate significantly lower depressive symptomatology among women, but not among men, residing in kibbutz communities. The women's lower level of depressive symptoms appears to be a result of better physical and mental functioning among kibbutz members and of such favorable lifestyle characteristics as frequent contact with their children among old-age kibbutz residents., Discussion: Both lifetime and current living conditions contribute to better mental health of women in the kibbutz at older ages.

Background: Due to multiple chronic illness and disability, the elderly consume a disproportionately large share of medications., Objectives: To assess the patterns and determinants of drug use among the community dwelling old-old population., Methods: The study population included 1,369 old-old persons from the baseline data of the Cross-Sectional and Longitudinal Aging Study (CALAS), which is based on a national random stratified sample of the Israeli Jewish population aged 75-94 years., Results: The mean number of drugs used by the study population was 3.3, and only 12.5% did not consume any drugs, Multivariate linear regression analysis showed that women used significantly more drugs than men, and that those born in Europe took significantly more drugs than those born in Israel and Asia-Africa. The number of medical conditions was the strongest predictor of drug use. Hospitalizations during the last year and frequent visits to family physician were also significant factors related to drug use. All variables combined explained 40% of the variance in drug use by the old-old. The most commonly used therapeutic groups were cardiovascular drugs (53%), psychotropic drugs (31%), analgesics (30%), and gastrointestinal drugs (28%)., Conclusions: Our data indicate that in addition to the association of drug use with health status and healthcare utilization, the number and type of drugs taken vary with gender and place of birth.

In this study, a method of taking one blood pressure reading using a sphygmomanometer was compared with a method of taking multiple successive readings using an automatic device. With multiple readings the blood pressure tended to be lower and fewer patients were classified as hypertensive. Using an automatic blood pressure recording device seems to be a practical way of achieving multiple readings in a busy clinic setting.

The authors examined the rate and correlates of depressive symptoms among community-dwelling oldest-old citizens in Israel with a sample of about 1,200 Jewish Israelis age 75-94. The estimated national rate of depressive symptoms was 43.5%. Significantly higher rates of depressive symptoms were found in women (52%, vs. 29.5% for men) and those of low educational level, low income, and Middle Eastern or North African origin. Having more depressive symptoms was associated with 1) all measures of impaired health status; 2) the psychosocial factors of living alone or with a nonspouse, having no available caretaker, and social and physical inactivity; 3) the following health behavior and habits: poor sleep, skipping meals, sexual inactivity, and drinking no alcohol; and 4) traumatic life events and immigration after age 20. The rate of depressive symptoms is relatively high among oldest-old citizens in Israel, possibly because of the immigrant nature of this population., (Copyright © 1996 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Advances in molecular biology techniques suggest that many haematological neoplasms originate from a transformation process at the level of the haemopoietic pluripotential stem cell. While familial aggregation has been reported for many haematological neoplasms, most studies were uncontrolled and examined the presence of the same haematological neoplasm as the index case. We assessed the familial aggregation of all haematological neoplasms in 4061 family members of 189 patients with various haematological neoplasms and two control groups: 955 relatives of 36 patients with non-malignant haematological disorders and 508 relatives of 33 patients with type II diabetes mellitus. Data collection included self-administered questionnaires. The odds ratio for haematological neoplasms among relatives of the index cases adjusted for age, sex, ethnicity, number of relatives in the family, and degree of familial linkage in the study group versus the two control groups was 3.62 (95% confidence interval, 1.44-9.07; P < 0.01). The vast majority of the haematological neoplasms among family members did not belong to the same histopathological category as the index cases. The data support the hypothesis of a genetic predisposition to haematological neoplasms. The fact that the aggregation is not disease specific is consistent with a defect in the pluripotent haemopoietic stem cell.

In the Dan and Ashkelon areas of Israel, 28 male and 24 female mild to moderate hypertensives without target organ damage aged 35-65 years were randomly assigned to treatment programmes (based on nutritional management, exercise and stress management techniques) either on an individual basis administered by physician-nurse teams (PN) or on a group basis from a team of paramedical professionals (PP) consisting of a psychologist, nutritionist and physical activity instructor. At 11 and 24 months follow-up, there were similar significant improvements in both treatment modes for such risk factors as body mass index, caloric intake and physical activity levels. There was a significant decrease in drug use from $36.28 a month at baseline to $18.94 a month at 11 month follow-up (P = 0.01) and to an estimated $20.48 at 24 months. Mean BP remained unchanged, despite the reduction in drug use, indicating a reduction in the underlying BP. The net present value (NPV) of the reduction in drug utilisation totalled $740 per person over a five year time horizon and a 7.5% discount rate. The total extra costs of treatment, training, case-note writing, travelling and follow-up booster sessions, amounted to $95 per patient for the PN mode and $234 per patient for the PP mode, yielding benefit to cost ratios of 7.79/1 and 3.16/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A comprehensive programme of nonpharmacological control of hypertension (balanced nutrition, satisfactory weight, enhanced physical activity, relaxation technique, smoking cessation) by primary care physician-nurse (PN) teams who were instructed and routinely advised by a paramedical professional (PP) team (psychologist, nutritionist and physical activity instructor) was developed with the aim of increasing long-term compliance. To evaluate effectiveness, 52 mild and moderate hypertensives without target organ damage were randomly allocated to six weekly meetings of individual intensive instruction by PN teams alone, or direct group instructions by PP teams (24 and 28 patients, respectively). The respective results at 11 months and 24 months follow-up compared with baseline were: (1) 56.9% and 58.8% showed minimal satisfactory reduction of weight, (2) 49% and 58.8% showed minimal satisfactory increase in physical activity, (3) the reported increase in physical activity at 11 months follow-up was validated by significantly correlated improved performance in ergometry, (4) 75% and 40% of the patients performed relaxation vs. 2% at baseline and (5) 71% and 59% needed no medication or reduced dose to control BP, and these changes were significantly (P < 0.02) correlated with weight reduction and increased physical activity. As no differences were found between the two modes of treatment, we conclude that our programme can be successfully applied by the PN primary care teams to increase adherence to nonpharmacological measures in the control of hypertension.

We examined the pattern of hospital stay in a pediatric division of a major teaching medical center in terms of justification of the hospital stay. Hospital stay days of all children admitted during 3 consecutive weeks were assessed prospectively according to predetermined criteria. Of the 2,048 hospital stay days 26% were unjustified, primarily due to unnecessary in-hospital follow-up and diagnostic evaluation that should have been carried out on an ambulatory basis. Logistic regression analysis revealed that neurological disorders and trauma, age younger than 3 years, specific ward, and the attending physician were significant predictors for unjustified hospital stay days. This method is proposed as a means for optimal reduction of redundant hospital stay and concomitant unnecessary economic burden.

Background: The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies., Methods and Results: In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids., Conclusions: Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.

Hypertension and glucose intolerance, determined in a random population sample (n = 2,475), showed a highly significant (P less than 0.001) association from the mildest levels of both conditions, independent of the confounding effects of age, sex, obesity, and antihypertensive medications. Summary rate ratios for hypertension were 1.48 (1.18-1.87) in abnormal tolerance and 2.26 (1.69-2.84) in diabetes compared with normal tolerance. Altogether, 83.4% of the hypertensives were either glucose-intolerant or obese--both established insulin-resistant conditions. Fasting and post-load insulin levels in a representative subgroup (n = 1,241) were significantly elevated in hypertension independent of obesity, glucose intolerance, age, and antihypertensive medications. The mean increment in summed 1- and 2-h insulin levels (milliunits per liter) compared with nonobese normotensives with normal tolerance was 12 for hypertension alone, 47 for obesity alone, 52 for abnormal tolerance alone, and 124 when all three conditions were present. The prevalence of concentrations (milliequivalents per liter) of erythrocyte Na+ greater than or equal to 7.0, K+ less than 92.5, and plasma K+ greater than or equal to 4.5 in a subsample of 59 individuals with all combinations of abnormal tolerance obesity and hypertension was compared with those in 30 individuals free of these conditions. Altogether, 88.1% of the former vs. 40.0% of the latter group presented at least one of these three markers of internal cation imbalance (P less than 0.001). We conclude that insulin resistance and/or hyperinsulinemia (a) are present in the majority of hypertensives, (b) constitute a common pathophysiologic feature of obesity, glucose intolerance, and hypertension, possibly explaining their ubiquitous association, and (c) may be linked to the increased peripheral vascular resistance of hypertension, which is putatively related to elevated intracellular sodium concentration.

A representative sample (n = 1211) of the Jewish population in Israel age 40-70 (excluding known diabetics), underwent a glucose tolerance test. Insulin response was found to be independently and positively associated with the GOH conditions--glucose intolerance (p less than 0.001), obesity (p less than 0.001), and hypertension (p less than 0.01) and with elevated serum uric acid (p less than 0.001) after accounting for the effects of sex, age, serum creatinine and use of antihypertensive medications. In a representative subgroup of 542 individuals, total VLDL and LDL fractions were estimated by standardized values (based on the reference group--individuals free of the GOH conditions), of their cholesterol and triglyceride components. Hyperinsulinemia was characterized by jointly elevated VLDL and LDL with reduced HDL. The risk ratio for this pattern (adjusted for the effects of age, sex, smoking and presence of any of the GOH conditions) was 3.4 (p less than 0.001). There was no further association of this disturbed lipoprotein profile with the GOH conditions. Cation concentrations were determined in a stratified subsample (n = 89) of the study group. The subsample comprised 30 individuals in the reference group, and 59 representing each of the seven possible combinations of abnormal glucose tolerance, obesity and hypertension (GOH group). Rate of cation imbalance defined as presence of at least one of three cation concentration--red blood cell sodium greater than or equal to 7.0 mEq/l, red blood cell potassium less than 92.5 mEd/l or plasma potassium greater than or equal to 4.5 mEq/l was 88.1% in the GOH, compared to 40.0% in the reference group (p greater than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma very low density lipoprotein (VLDL) cholesterol and triglyceride, low density lipoprotein (LDL) cholesterol and triglyceridea, high density lipoprotein (HDL) cholesterol, glucose and insulin response (sums of 1- and 2-hour postload oral glucose levels), body mass index (BMI), and blood pressure were determined in a representative sample (n = 542) of the adult Israeli Jewish population. Persons with diabetes or on antihypertensive medications were excluded. Total VLDL and LDL fractions were estimated from their cholesterol and triglyceride subfraction levels that were standardized relative to the mean of the reference group (participants free of glucose intolerance, obesity, and hypertension--the GOH conditions). Hyperinsulinemia and disturbed levels of VLDL and LDL were defined as levels equal to or greater than the 75th percentile and those of HDL, equal to or less than the 25th percentile of their respective reference group distributions. When VLDL was disturbed jointly with LDL and HDL, the mean insulin response adjusted for age, gender, glucose response, BMI, blood pressure, and smoking was high compared to the reference group (166.0 vs. 122.5, p less than 0.001). With isolated disturbed VLDL, or disturbed LDL and HDL but normal VLDL, the mean insulin response resembled the reference group. The adjusted risk ratio for this jointly disturbed lipoprotein profile among hyperinsulinemic individuals was 3.4 (95% confidence limits 2.6 to 4.4, p less than 0.001) with no further association with the GOH conditions. We conclude that hyperinsulinemia is characterized by an atherogenic lipoprotein profile.