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Study Design: This was an observational study., Objective: This study aims to explore sociodemographic and regional geographic variations in lower back pain (LBP) incidence, prevalence, and burden in the United States (US from 2000 to 2019)., Summary of Background Data: LBP is a major contributor to lost wages and disability in the United States. As LBP is associated with increasing age and sedentary lifestyle, the incidence of LBP is expected to rise. Due to LBP's multifactorial causes, US epidemiological trends lack sufficient data., Materials and Methods: Descriptive epidemiological data including disability-adjusted life years (DALYs), incidence, and prevalence per 100,000 population from 2000 to 2019 were collected from the Global Burden of Disease database. State-level data regarding poverty, insurance and employment status were obtained from the US Government Census Bureau and US Department of Labor. Statistical significance was indicated by P <0.05., Results: From 2000 to 2019, the US demonstrated reductions in LBP incidence, prevalence, and DALYs. Regional analysis demonstrated the Midwest to have the greatest mean incidence, prevalence, and DALYs; with Midwestern females significantly more affected than females in other regions. Those aged 25 to 49 in the Midwest were impacted significantly more across all measures compared with age-matched populations in other regions. Nationally, there were no significant associations between unemployment and LBP. Poverty was inversely correlated with LBP incidence. Uninsured status was positively correlated with prevalence and DALYs., Conclusion: Although there has been progress in reducing the impact of LBP in the United States, the Midwest region has greater rates for all measures compared with other US regions. Further, females and those aged 25 to 49 in the Midwest were more likely to be affected by LBP compared with counterparts in other regions. Future studies should identify specific factors contributing to elevated LBP rates in the Midwest in order to guide targeted interventions to reduce the incidence and burden of LBP there., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Carotid free-floating thrombus (FFT) is very rarely diagnosed in patients with acute ischemic stroke. It is a real clinical emergency due to the significant risk of death associated with thromboembolic complications. Herein, we present three patients with ischemic stroke caused by carotid FFT after less than 20 days from administration of mRNA vaccine BNT162b1 (Pfizer/BioNTech) for Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV-2). To our knowledge, these are the first cases reporting carotid FTT following SARS-CoV-2 vaccination., (© 2022. Fondazione Società Italiana di Neurologia.)

Introduction: The study aimed to identify the main prognostic factors in diabetic patients with ischemic stroke undergoing reperfusion therapies (RT)., Methods: This retrospective study included 170 diabetic patients: 62 treated with intravenous thrombolysis (IVT) alone and 108 with mechanical thrombectomy (MT). Among MT patients, 29 underwent IVT. We collected clinical, laboratory, and radiological data. The outcomes were 3-month functional impairment (measured by modified Rankin scale, mRs), discharge neurological severity (measured by National Institutes of Health Stroke Scale score, NIHSS), 3-month mortality, intracranial hemorrhage (ICH), and symptomatic intracranial hemorrhage (SICH). We performed a general analysis for all RT and sub-group analyses for IVT and MT., Results: A lower mRs was associated with lower glycemia and admission NIHSS (aNIHSS) in all RT and MT; lower aNIHSS and younger age in IVT. Mortality increased with hyperglycemia, aNIHSS, and age in all RT; age and aNIHSS in IVT; hyperglycemia and systolic pressure in MT. A lower discharge NIHSS was related with lower aNIHSS, thrombolysis, and no thrombectomy in all RT; lower aNIHSS in IVT; lower aNIHSS and thrombolysis in MT. ICH was associated with elevated aNIHSS, older age, and lower platelets in all RT; lower platelets and older age in IVT; higher aNIHSS in MT. SICH depended on longer thrombectomy duration in all RT; no metformin use in IVT; higher weight in MT., Conclusion: The study shed light on diabetic patients and stroke RT highlighting the protective effect of metformin in IVT and the role of glycemia, weight, and combined treatment in MT., (© 2022. Fondazione Società Italiana di Neurologia.)

Data regarding repeated reperfusion therapy (rRT) in acute ischemic stroke (AIS), including intravenous thrombolysis and endovascular treatment (EVT), are quite poor. To date, there are only few case reports and five larger studies on repeated EVT. We aimed to report our single-center experience and describe different clinical scenarios of recurrent AIS with emergent large vessel occlusion (LVO), for which the decision-making process could be challenging in the emergency setting. We retrospectively reviewed 765 consecutive AIS patients with LVO, who underwent reperfusion procedures at our comprehensive stroke center, from 2014 to 2020, and identified rRT patients. We identified and reviewed the medical records of eight patients (1.05%), who repeated reperfusive treatment for recurrent stroke within 30 days (early arterial reocclusion, EAR) and after 30 days (late arterial reocclusion, LAR). We assigned collected data to three clinical scenarios, each divided into EAR and LAR cases. All patients had recurrent emergent LVO in the same vessel territory previously affected, both in EAR and LAR patients. A good clinical outcome has been achieved in EAR patients (modified Rankin Score ≤ 2). Artery-to-artery embolic mechanism was more common in the EAR group, while LAR was more frequently associated with cardioembolic source. RRT appears to be an effective treatment option for recurrent LVO, and it should not be withheld in carefully selected patients. EVT should be considered, including aspiration-only and stenting procedures in patients with AIS and recurrent LVO after previous reperfusive treatments, even after a very short time., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Pulmonary opacities are described in many chest radiograph reports in stroke patients and are often asymptomatic. The aim of this study is to investigate the clinical features associated with asymptomatic pulmonary opacities (APO) and evaluate APO prognostic value in ischemic stroke., Methods: We prospectively analyzed patients with acute ischemic stroke without pneumonia symptoms referred to our stroke center. All patients underwent a chest x-ray within 48 hours after admission. We divided patients with APO (defined as asymptomatic area of increased pulmonary attenuation) and patients without APO. Firstly, we compared clinical, laboratory, and echocardiographic parameters between groups; secondly, APO were evaluated as a possible predictor of the neurological severity at discharge and functional outcome at 90 days., Results: We included 162 patients, 78 of whom had APO. On univariate analysis, we observed a significant difference between patients with APO and patients without APO in terms of neutrophils (73,56±10,10 vs 69,72±12,29; p=0,031), atrial fibrillation (AF, paroxysmal 27,4% vs 25,6%; permanent 19% vs 2,6%; p<0,002), cardioembolic etiology (37,2% vs 22,7%, p <0,033), thrombectomy (58,3% vs 42,9%, p <0,05), dysphagia/vomit (34,5% vs 14,10%, p<0,005), admission NIHSS (14,20±5,98 vs 10,29±5,82, p=0,001), discharge NIHSS (8,68±6,73 vs 5,64±6,20; p=0,003), and 90 days mRS (3,47±2,12 vs 2,31±1,93; p=0,001). On multivariate analysis, APO were significantly associated with admission NIHSS and AF. APO were a predictor of outcome on univariate analysis, but not on multivariate., Conclusion: APO in acute ischemic stroke are associated with AF. APO were not a predictor of neurological and functional outcome., Competing Interests: Disclosure of interest The authors report no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The symptoms related to insular ischemia have been the object of several studies in patients affected by stroke, although they are often accompanied by other ischemic alteration of adjacent brain structures supplied by the middle cerebral artery (MCA). The insula is vulnerable because of an ischemia due to thromboembolic vascular occlusion of the M1 MCA segment and the 2 main MCA branches (M2), mainly when they abruptly arise from the principal stem at a right angle. This topographical and anatomical peculiarity could enable an embolic formation, especially due to atrial fibrillation (AF), to occlude the transition pathway between M1 and M2, while the proximal origin of vascular supply protects the insula from ischemia due to hemodynamic factors. The aim of the study is to characterize the clinical aspects of acute ischemic strokes as a first event in the insular territory with specific attention to atypical manifestation. We have considered 233 patients with a first event stroke involving the insular territory and 13 cases of isolated insular stroke (IIS), from the stroke registry of the Policlinico "G.Martino", University of Messina, between the February 10, 2014 and the February 7, 2018. IIS patients showed CT/MRI lesions restricted to the insular region. Exclusion criteria were coexisting neurological diseases, structural brain lesions, extension to the subinsular area >50% of the total infarct volume. We identified 13 IIS patients (mean age 74 years), with an isolated symptom or a combination of typical and atypical aspects. Furthermore, we observed high frequency detection of cardiac disturbances. To our knowledge, just a few previous studies have described IIS; their incidence is still not well defined. IIS manifested with a combination of deficits including motor, somatosensory, speaking, coordination, autonomic and cognitive disturbances. After an ischemic stroke, AF manifestation could follow briefly the major event and its duration could be very short, as an autonomic dysfunction due to an insular infarction. This clinical condition requires a continuous cardiac monitoring for this dangerous occurrence., (© 2020 S. Karger AG, Basel.)

The term hemiballism-hemichorea refers to a movement disorder characterized by involuntary movements, often violent, described as uncontrollable jerking, flinging, flailing or kicking, involving proximal muscles of a limb and it is often associated with lesions in the subthalamic nucleus. In this report, we described three cases of hemiballism-hemichorea as the first manifestation of acute ischemic stroke with lesion in the frontoparietal region on brain MRI and no involvement of the subthalamic nucleus. One patient was treated with thrombolysis and recovered within one hour. The other patients recovered within 48 h from symptoms onset. The impairment of the recently described "hyperdirect way", in which the cortical signal reach directly the subthalamic nucleus, may underlie the symptoms. We support, with a clinical point of view, the role of the frontoparietal region in the genesis of the hemiballism-hemichorea. An acute onset of this symptom should lead to think to an acute stroke., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: We conducted a study to describe food profile, health status and stroke risk factors in the population of the Aeolian Islands., Design: Self-administrated questionnaires regarding eating habits, health status and stroke risk factors were obtained from a sample of the general Aeolian population. We analysed the difference from common healthy eating habits indicated by the Italian Institute of Nutrition., Setting: Current evidence finds the Mediterranean diet is a protective factor for cardio- and cerebrovascular diseases. The Aeolian Islands are an interesting study setting because of their peculiarity in the epidemiology of cerebrovascular and neurodegenerative diseases., Participants: Individuals (n 586; age range 15-93 years; mean 52 (sd 18) years) living in the Aeolian Islands., Results: We found low fish consumption in 13·3% and vitamin intake deficiency in 5·8% of participants. A marked excess of saturated fats was observed in 71·0% of participants. Sodium excess was reported almost in half of participants (49·0%). Eating habits were characterized by high consumption of fruits and vegetables, consistent use of olive oil and scanty use of cured meat. Health status as evaluated by the General Health Questionnaire was characterized by 'normal distress' level in the majority of participants., Conclusions: Study findings show the eating habits and health status of the Aeolian people in an interesting setting of low incidence of cerebrovascular disease. This nutrition regimen has been proved to be protective against cerebrovascular disease. Nutrition is likely to contribute to the low incidence of stroke in this population.

Background: Acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) represents 1-4% of all ischemic strokes. BAO results in strokes associated with a high risk of a poor functional outcome and, in 86-95% of the untreated cases, it results in death because of the vital cerebral structures involved. Diagnosis can be delayed because of the variability in presenting symptoms, and acute treatment is often attempted even beyond 6 h from symptoms onset because of the high risk of a fatal prognosis., Objective: In this observational study, we retrospectively analyzed patients with AIS due to BAO referred to the stroke center of the University Hospital of Messina. We aimed to assess prognostic factors and to evaluate the association between clinical outcome and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) and collateral status., Method: BAO was confirmed by cerebral computed tomography (CT) angiography or cerebral angiography. All patients underwent CT scan and magnetic resonance imaging (MRI). We assessed the pc-ASPECTS on diffusion-weighted imaging (DWI) MR images and the Posterior Circulation Collateral Score (PC-CS) for every patient. Functional outcome was assessed at 3 months using the modified Rankin Scale (mRS)., Results: The study population consisted of 27 patients; 16 males and 11 females. The mean age was 66 (±14) years. We observed a favorable outcome (mRS 0-3) in 40.7% of cases, 25.9% reached mRS 0-2, and 29.6% had a poor clinical outcome (mRS 4-5). Patient survival was 70.4%, whereas 8 patients died (29.6%). In 7 patients, pc-ASPECTS was ≥7. According to the PC-CS, 33.3% had moderate collaterals and 63.0% had good collateral status prior to receiving the treatment. Favorable outcome was significantly associated with age, NIHSS score at admission, pc-ASPECTS, hypercholesterolemia, and female sex but not with the other risk factors., Conclusions: In our study, we found that younger age, low NIHSS score at admission, and high pc-ASPECTS, but not onset to treatment time, are associated with a favorable clinical outcome. Transferred patients did not have a significantly poorer outcome. These findings confirm that acute stroke treatment improves clinical outcome in BAO patients, in spite of a delayed diagnosis and an extended therapeutic window, considering lesion volume and localization in DWI MRI., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Metapopulations persist when local populations are rapidly recolonized following local extinctions. Such persistence requires asynchrony; simultaneous crashes of all populations would leave no source of recolonization. We show theoretically and experimentally that catastrophic population extinctions themselves can promote metapopulation persistence, by preventing spatial synchrony and thus enhancing recolonization. We refer to this behaviour as the 'spatial hydra effect': as with the mythical hydra that grows two new heads when one is removed, extinctions can increase recolonization. The effect is robust, occurring in a wide range of theoretical models exhibiting cyclic or quasi-cyclic population dynamics. In a laboratory microcosm experiment using cyclic protist predator-prey metapopulations, catastrophic perturbations wiping out populations but leaving the patch otherwise unchanged increased metapopulation persistence when high dispersal rates would otherwise have led to spatially synchronous extinctions of all populations. We discuss several candidate examples of the spatial hydra effect in nature.

Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS)., Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD., Design, Setting, and Participants: A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine., Main Outcomes and Measures: Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS., Results: Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P < .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainous patients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P > .99)., Conclusions and Relevance: In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.

Objective: To estimate whether there is a correlation between family history of venous thromboembolism and factor V Leiden mutation carriage in gravid women without a personal history of venous thromboembolism., Methods: This is a secondary analysis of a prospective observational study of the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden mutation. Family history of venous thromboembolism in either first- or second-degree relatives was self-reported. Sensitivity, specificity, and positive and negative predictive values of family history to predict factor V Leiden mutation carrier status were calculated., Results: Women without a personal venous thromboembolism history and with available DNA were included (n=5,168). One hundred forty women (2.7% [95% confidence interval (CI) 2.3-3.2%]) were factor V Leiden mutation-positive. Four hundred twelve women (8.0% [95% CI 7.3-8.7%]) reported a family history of venous thromboembolism. Women with a positive family history were twofold more likely to be factor V Leiden mutation carriers than those with a negative family history (23 of 412 [5.6%] compared with 117 of 4,756 [2.5%], P<.001). The sensitivity, specificity, and positive predictive value of a family history of a first- or second-degree relative for identifying factor V Leiden carriers were 16.4% (95% CI 10.7-23.6%), 92.3% (95% CI 91.5-93.0%), and 5.6% (95% CI 3.6-8.3%), respectively., Conclusion: Although a family history of venous thromboembolism is associated with factor V Leiden mutation in thrombosis-free gravid women, the sensitivity and positive predictive values are too low to recommend screening women for the factor V Leiden mutation based solely on a family history.

We report a case of a 76-year-old woman admitted to our institution with sudden onset of dizziness and vertigo followed by vomiting and blurred vision. Her medical history was remarkable for hypertension, diabetes, and ischemic stroke in the territory of the left cerebral median artery. Her symptoms were suggestive of a cerebellar stroke. Computed tomography brain scan and neck vessel ultrasounds produced normal findings. A 24-hour blood pressure monitoring showed a reverse dipping pattern. Magnetic resonance imaging examination was performed, showing a hyperintense ischemic focus involving pons and left middle cerebellar peduncle, on T2-weighted images. On Time-of-flight (TOF)-3-dimensional magnetic resonance angiography, there was a marked reduction of basilar artery signal. The digital subtraction angiography showed a vertebrobasilar system anomaly. The right vertebral artery was hypoplastic with few thin terminal spinal branches. The left vertebral artery was vicarious to the right one in intracranial tract. V3 to V4 tract showed multiple atherosclerotic wall irregularities. The basilar common trunk was absent. An abnormal posterior inferior cerebellar artery replaced the anterior inferior cerebellar artery and superior cerebellar artery. Right posterior inferior cerebellar artery, anterior inferior cerebellar artery, and superior cerebellar artery arose from ipsilateral V4 tract. This case is the first description of pure basilar agenesia. The symptoms might be related to temporary decrement of the flow in the left vertebral artery. Furthermore, the reverse dipping pattern together with the aging, hypertension, and diabetes had probably contributed to a hemodynamic malfunction of the cerebral vascular system., ((c) 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up ( P = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI > or = 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI.

Objective: To assess whether there are evident adverse effects of 17 alpha-hydroxyprogesterone caproate after in utero exposure., Methods: This study evaluated surviving children of mothers who participated in a multicenter placebo-controlled trial of weekly intramuscular 17 alpha-hydroxyprogesterone caproate, with a 2:1 allocation to 17 alpha-hydroxyprogesterone caproate and placebo, respectively. The guardian was interviewed about the child's general health. Children underwent a physical examination and developmental screen with the Ages and Stages Questionnaire. Gender-specific roles were assessed with the Preschool Activities Inventory., Results: Of 348 eligible surviving children, 278 (80%) were available for evaluation (194 in the 17 alpha-hydroxyprogesterone caproate group and 84 in the placebo group). The mean age at follow-up was 48 months. No significant differences were seen in health status or physical examination, including genital anomalies, between 17 alpha-hydroxyprogesterone caproate and placebo children. Scores for gender-specific roles (Preschool Activities Inventory) were within the normal range and similar between 17 alpha-hydroxyprogesterone caproate and placebo groups., Conclusion: 17 alpha-hydroxyprogesterone caproate seems to be safe for the fetus when administered in the second and third trimesters.

Evidence exists that BRCA2 carriers may have an elevated risk of breast, ovarian, colon, prostate, and pancreatic cancer. In general, carriers are defined as individuals with protein truncating mutations within the BRCA2 gene. Many Brca2 knockout lines have been produced and characterized in the mouse. We previously produced a rat Brca2 knockout strain in which there is a nonsense mutation in exon 11 between BRC repeats 2 and 3, and a truncated protein is produced. Interestingly, while such a mutation in homozygous mice would lead to limited survival of approximately 3 months, the Brca2-/- rats are 100% viable and the vast majority live to over 1 year of age. Brca2-/- rats show a phenotype of growth inhibition and sterility in both sexes. Aspermatogenesis in the Brca2-/- rats is due to a failure of homologous chromosome synapsis. Long-term phenotypes include underdeveloped mammary glands, cataract formation and lifespan shortening due to the development of tumors and cancers in multiple organs. The establishment of the rat Brca2 knockout model provides a means to study the role of Brca2 in increasing cancer susceptibility and inducing a novel ocular phenotype not previously associated with this gene.

Objective: To evaluate whether women who agree to future use of their biologic specimens for genetic studies reflect the larger study population from which they are derived., Methods: Women were questioned as to the future disposition of their maternal and fetal DNA samples upon enrollment in a multicenter, observational study originally designed to identify factor V Leiden mutation carriers and prospectively ascertain the estimated rate of pregnancy-related venous thromboembolism and adverse pregnancy outcome. Univariate and multivariate analyses was carried out on the 5,003 of 5,188 enrolled women who indicated their desire regarding future disposition of their DNA samples., Results: Among these 5,003 women, 20.1% desired that their samples be discarded and not available for future genetic studies. Multivariate analysis demonstrated that women who agreed to subsequent use of samples were less likely African-American (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.7) or Hispanic (OR 0.4, 95% CI 0.3-0.5), and more likely to use tobacco (OR 1.2, 95% CI 1.0-1.6) than those who desired that their samples be discarded., Conclusion: Genetic samples from women agreeing to their use in a sample repository may not be representative of the index study cohort. This should be considered in their subsequent interpretation and generalizability., Level of Evidence: III.

Identification of high-penetrance breast cancer genes such as Brca1 has been accomplished by analysing familial cases. However, these genes occur at low frequency and do not account for the majority of genetic risk. Identification of low-penetrance alleles that occur commonly in populations may benefit from unbiased genome-wide screening. One such approach uses linkage studies in rodent models to identify homologous human candidates. The Wistar Kyoto (WKy) rat is resistant to mammary carcinomas induced with 7,12-dimethybenz[a]anthracene (DMBA), whereas the Wistar Furth (WF) strain is susceptible. Previous genome-wide linkage studies in crosses of these strains identified three WKy resistance quantitative trait loci, Mcs5, Mcs6 and Mcs8, and one predicted to increase susceptibility, Mcs7. The Mcs7 region on rat chromosome 10 (RNO10) is orthologous to human 17q, a common site of genetic aberrations in breast cancer. Here, we establish the independent phenotype conferred by Mcs7 using congenic rats carrying the WKy Mcs7 locus on a WF background. Tumor multiplicity was significantly higher ( approximately 50%) in DMBA-treated congenics homozygous and heterozygous for the WKy allele at the Mcs7 locus, compared to controls. We also investigated allelic imbalance (AI) in mammary carcinomas from (WKy x WF)F1 rats and Mcs7 heterozygous congenics. Of the four known WKy Mcs loci tested, only Mcs7 displayed AI. The pattern of AI in carcinomas from both F1 and Mcs7 congenic rats was similar, suggesting a WF allelic loss. Together, these data suggest that one or more breast cancer-related genes are located within the dominantly acting WKy allele at the Mcs7 locus.

Although previous national surveys have shown an increase in the use of complementary and alternative medicine (CAM) in the U.S. population, racial and ethnic minority populations were under-represented in these surveys. As a result, a profile of the CAM user as white, female, affluent, middle-aged and well educated has emerged. Representing the mainstream population, these previous studies did not take into account the racial and ethnic minority populations who may have their own healing traditions and who may hold different beliefs, use different terminology, and have unique patterns of CAM use. In partnership with community-based organizations and community residents, a culturally sensitive survey instrument and protocols were designed and tested to gather data on lower income, urban African-Americans' use of, attitudes toward, and understanding of CAM. The major findings of this pilot research are 1.) Community-partnered research can help researchers gain access to sensitive data and design culturally appropriate studies; 2.) CAM terminology varies by cultural group; 3.) Certain forms of CAM (folk or family practices) are commonly found in African-American populations; and 4.) Factors that affect CAM use--including age, lack of access to conventional medicine, cultural heritage, and dissatisfaction with conventional medicine.

In the emerging health care environment, families and communities are facing a broad range of conditions that require more integrated views of wellness and illness, mind and body, and the biomedical and the behavioral. This also calls for an enhanced care delivery system. Three interfacing areas of practice have particular significance for the psychiatric-mental health nursing workforce: enhanced primary care, public health or population-focused health interventions, and managed care. This paper addresses the broad range of knowledge, skills, and competencies that are required for the future of advanced practice psychiatric-mental health nursing and describes interactive learning experiences and new pedagogies to deliver them.

Endometriosis is a disease in which uterine tissue proliferates in extrauterine sites. Using a surgical model to simulate endometriosis, we explored the potential for the phytoestrogen genistein, by injection and diet, to sustain endometriosis in rats. Uterine tissue was attached to intestinal mesentery of 8-week-old Sprague Dawley rats. After 3 weeks, the rats were ovariectomized and the implants measured. Following 3 weeks of daily injections or exposure to dietary genistein, animals were necropsied and implants located and measured. Injections of genistein (50 and 16.6 microg/g BW) or estrone (1 microg/rat) sustained the implants; injection of sesame oil (vehicle for estrone), dimethylsulfoxide (DMSO; vehicle for genistein), or genistein at 5.0 microg/g BW did not sustain implants. Dietary genistein (250 or 1000 mg genistein/kg AIN-76A diet) did not support the implants. In ovary-intact rats exposed to 250 mg genistein/kg AIN-76A diet, implant size was not altered, compared to control-fed animals. To assess estrogenic actions of genistein, we measured uterine estrogen receptor alpha (ER-alpha) and progesterone receptor (PR) isoforms A and B by Western blot analyses. Injections of estrone or genistein (50 or 16.6 microg/g BW) significantly reduced uterine ER-alpha compared to vehicle-treated animals. PR (B) was significantly increased by all injected doses of genistein or estrone and by the higher dietary dose (1000 mg genistein/kg AIN-76A). PR (A) was significantly increased by injected doses of genistein (16.6 and 5.0 microg/g BW). We conclude that pharmacologic injections, but not dietary physiological concentrations of genistein, support surgically induced endometriosis in rats. Our results suggest a critical role for ER modulation and genistein bioavailability in the maintenance of the implants.

We evaluated the mechanism of action by the phytoestrogen genistein in the prepubertal rat uterus, when administered pharmacologically or physiologically. Female rats were injected with genistein (500 microg/g body weight), estradiol benzoate (EB) (500 ng/g body weight) or vehicle, dimethylsulfoxide (DMSO), on days 16, 18, and 20 postnatal. In 21-day-old rats, both compounds increased circulating estradiol and decreased progesterone concentrations. Uterine estrogen receptor alpha (ER-alpha) and androgen receptor (AR) proteins were reduced, and progesterone receptors (PR) were increased, as measured by western blot analyses. Immunohistochemistry for ER-alpha was confirmatory. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated a decrease in ER-alpha, but not in ER-beta, PR and AR mRNA levels following genistein treatment. In prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or 250 microg estradiol per kg diet, uterine ER-alpha, AR, and PR proteins were not altered significantly. We conclude that pharmacologic, but not physiologic concentrations of genistein can modulate sex steroid receptor expression in the rat uterus.

This paper will describe one of the major trends in health care delivery: family oriented primary care. Implications and future directions for practice, education and research in the United States and Germany will be described and contrasted. The paper is a result of an ongoing dialogue between the first author, a Fulbright Professor at the University of Witten/Herdecke, and the second and third authors. The authors believe that, contextualizing emerging trends in health care delivery in this way, helps to clarify both what is unique to each country and what is actually or potentially shared in common.

Asian women and men who consume a traditional diet high in soy products have low incidences of breast and prostate cancers, respectively. Yet Asians who immigrate to the United States and adopt a Western diet lose this protection. We investigated the potential of genistein, a component of soy, to protect against breast cancer and to cause reproductive and developmental toxicity. Our study showed that injections of genistein in rats during the prepubertal period resulted in a 50% reduction of chemically induced mammary tumorigenesis. Studies in mammary whole mounts revealed that prepubertal genistein exposure resulted in fewer terminal end buds and more lobules type II. Cell proliferation in the terminal end buds of adult rats treated prepubertally with genistein was less than that in animals treated with the vehicle (dimethyl sulfoxide). Reproductive and developmental toxicity studies did not find significant alterations to fertility, number of male and female offspring, body weight, anogenital distance, vaginal opening, testes descent, estrus cycle, or follicular development. We concluded that pharmacologic doses of genistein given to immature rats enhance mammary gland differentiation, resulting in a significantly less proliferative gland that is not as susceptible to mammary cancer. We speculate that breast cancer protection in Asian women consuming traditional soy-containing diets is, in part, derived from early exposure to genistein-containing soy. We believe that early programming events are essential for cancer protection benefits.

We have previously demonstrated that exposure to genistein early in life protects against chemically-induced mammary cancer in rats. To gain insight into the mechanism of action, we have investigated the expression of the EGF-signaling pathway in the mammary glands of 21 and 50 day old rats treated on days 16, 18, and 20 postpartum with 500 microg genistein/g body weight (B.W.) or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO). This prepubertal genistein treatment up-regulated TGF-alpha and the EGF-receptor (EGFR), but not EGF, in mammary terminal ductal structures at day 21 postpartum. TGF-alpha, EGF and EGFR mRNA levels were similar in 21 day old control- and genistein-treated animals. At day 50 postpartum, mammary glands of genistein treated rats had more lobules and fewer terminal end buds (TEBs) and terminal ducts (TDs), i.e. they were more differentiated. TGF-alpha mRNA levels were down-regulated in TEB of proestrous and estrous females; EGF mRNA levels were down-regulated in TDs of proestrous, but not in estrous females; and EGFR mRNA levels were not altered in 50 day old proestrous or estrous female rats. EGFR immunostaining intensity was decreased in TEBs, but not in the total gland. EGF was increased in TEBs and TDs. TGF-alpha, EGF and EGFR were also observed in the stroma and fat pad, but genistein treatment did not alter the expression of these proteins in those locations. TGF-alpha, but not EGF and EGFR, immunostaining was observed in cell nuclei (not modulated by genistein), suggesting that this growth factor may act directly on nuclear events such as transcription and DNA replication. For comparative purposes, prepubertal diethylstilbestrol treatment was investigated and found to decrease EGFR immunostaining intensity and total IHC staining in all terminal ductal structures. We conclude that prepubertal genistein treatment directly stimulates TGF-alpha and EGFR to enhance mammary gland differentiation. This programs the differentiated cells for a down-regulated EGF-signaling pathway in TEBs and TDs of adult mammary glands. Reduced EGFR expression at time of carcinogen exposure may account for genistein programming against mammary cancer.

In the evolving health care environment, advanced practice opportunities for psychiatric-mental health nurses may lie in managed care models of community oriented primary health care. As providers, care managers, health promoters and educators, and client advocates with family systems expertise, psychiatric-mental health advanced practice specialists are a necessary component of all primary health care. This article describes the development of a community-based primary care practice that integrates physical and mental health care on the same site.

As changes in our health care system evolve, making the transition to greater parity of mental and physical health is paramount to move health care in the direction of prevention and health promotion. Although parity is the goal, the most feasible path to reaching it may lie in relinking mental health to physical health in managed care models of primary health care. This article identifies emerging directions in the mental health field and points to new opportunities for advancing the practice of psychiatric-mental health nurses.

Differences in distress within couples who have experienced the sudden death of a child were examined. Results from two independent samples (N = 50 couples and N = 60 couples) were compared. The SCL-90-R and the BSI were used to measure global psychological distress and distress in nine symptom dimensions. Paired t tests revealed similar findings in the two samples: Within couples, women had significantly greater global distress than men and significantly greater distress than men in most symptom dimensions. Hostility scores within couples were similar and indicated a high level of hostility. The findings may explain relational problems observed within bereaved couples. Interventions designed to help couples cope with their differences and their hostility may decrease relational problems.

Child custody litigation signals parental conflicts that have serious implications for a child's long-term development. The authors describe a family systems approach to child custody decision making--the contextual approach, derived from contextual family theory. A case study analysis and pilot study illustrate the use of the approach with a small group of families who turn to the legal system to resolve custody or visitation disputes. The findings suggest the approach's usefulness in helping families create alternatives to continued disputation. The findings also reinforce the need for further research to test the preventive potential of the approach in reducing returns to court.

To define the pharmacokinetics and pharmacodynamics of ritodrine after intramuscular injection, we administered 5 or 10 mg ritodrine into the gluteus or deltoid muscles of 12 pregnant volunteers. Six women received 5 mg and six received 10 mg into each muscle group on different days. We withdrew blood samples before and 12 times in the 6 hours after ritodrine injection. Blood pressure and heart rate were recorded at each time. Ritodrine was measured by high-performance liquid chromatography. Peak ritodrine concentrations (mean +/- SD) after a single 5 mg injection in the deltoid or gluteus were 38 +/- 13 and 26 +/- 8 ng/ml, respectively. After a 10 mg dose in the deltoid or gluteus, peak concentrations were 59 +/- 30 and 47 +/- 22 ng/ml, respectively. Although higher, the peak plasma concentrations after injections into the deltoid were not significantly greater than those after injection into the gluteus. None of the pharmacokinetic parameters differed according to dose or injection site. The pharmacodynamic effects of ritodrine were unaffected by injection site, but ritodrine caused a dose-related increase in heart rate and systolic blood pressure and a dose-related decrease in diastolic blood pressure. After a 10 mg injection, the maximal changes in heart rate, systolic, and diastolic blood pressure were 22%, 10%, and 19%, respectively. However, mean blood pressure was not altered by either the 5 or 10 mg dose. These findings indicate that there are few differences in pharmacokinetic parameters between deltoid and gluteal injection of ritodrine. The single intramuscular injection of 5 or 10 mg ritodrine results in labor-inhibiting concentrations with clinically insignificant cardiovascular effects.

The oral dosing regimen for ritodrine was based in large part on kinetic data obtained in nonpregnant subjects. There are limited kinetic data after oral administration of ritodrine in pregnancy. The purpose of the present study was to compare ritodrine kinetics in pregnant and nonpregnant women, evaluate the effect of feeding on ritodrine absorption in pregnant women, and determine if the plasma concentration of ritodrine is proportional to the dose administered in nonpregnant women. Plasma concentrations after a single 20 mg dose of ritodrine were significantly greater in fasting nonpregnant women than in fasting pregnant women. The area under the concentration time curve was 1372 +/- 385 and 1001 +/- 257 ng/ml/min, respectively. In pregnant women ingesting 20 mg of ritodrine, plasma concentrations were not significantly different in the fed or fasted state; plasma concentrations peaked at 11 ng/ml and were less than 3 ng/ml within 4 hours. In nonpregnant subjects the concentration of ritodrine in plasma was proportional to the dose. After ingestion of 10, 20, or 30 mg of ritodrine, the area under the curve was 751 +/- 253, 1372 +/- 385, and 2148 +/- 571 ng/ml/min, respectively. These data indicate that ritodrine concentrations in pregnant women after a 20 mg oral dose are low. Increases in dosage will probably result in proportional increases in plasma concentration. The maximal dose of ritodrine recommended for prevention of recurrent preterm labor should be increased.

Our experience suggests two significant benefits of shaping an international education focus in a nursing curriculum. First, a genuine understanding and appreciation of a foreign health care system is strengthened by identification of and confrontation with the socio-political context in which it is embedded. The second, and perhaps most fundamental benefit, is not so easy to verbalize. This involves the participant's personal confrontation with another culture. What is external, the experience of a foreign culture, translates into an encounter with the foreign territory of one's own thinking. The participant is challenged to overcome the traditional limitations of professional discipline, experience and vision and to move toward notions of world community and human solidarity. It seems to us that the development of concepts, resources and methods to move American nursing in the direction of greater solidarity with the world health care community is a legitimate task for nursing education.