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Mental health conditions constitute a major burden of disease for adolescents globally and can lead to significant adverse consequences. This systematic review aimed to identify if psychosocial interventions are effective in preventing mental health conditions in adolescents already experiencing emotional problems. We searched for randomized controlled trials comparing psychosocial interventions for preventing mental health conditions with care as usual in adolescents aged 10-19 who are experiencing symptoms of emotional problems. We searched PubMed/Medline, PsycINFO, ERIC, EMBASE, and ASSIA databases to identify studies. We found 82 eligible studies (n = 13,562 participants). Findings show that interventions can reduce mental health conditions and increase positive mental health. Across all reported time points, psychosocial interventions showed significant, small-to moderate-sized beneficial effects on preventing mental health conditions (SMD: -0.26, 95% CI [-0.42, -0.19] and small positive effects on positive mental health (SMD: 0.17, 95% CI [0.097, 0.29]. There were no statistically significant pooled findings suggesting that psychosocial interventions had either a positive or negative effect on self-harm or suicide; aggressive, disruptive and oppositional behavior; substance use; or school attendance. Despite the positive findings, a critical gap exists in the design of effective psychosocial interventions to reduce self-harm and suicide, and other risk behaviors in adolescents with symptoms of emotional problems., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Latinx youth are a population of concern, at elevated risk for chronic diseases and with poor adherence to dietary recommendations., Objectives: To examine Latinx seventh-grade students' perceptions of the factors that influence their diet and eating behaviors., Design: This qualitative research used focus groups and an inductive content analysis approach., Participants/setting: Five sex-stratified focus groups (three groups with females) with 35 primarily Latinx seventh-grade students were conducted at two local Title 1 public middle schools in a large metropolitan area of the Southwestern United States., Main Outcome Measures: The discussion protocol included questions about participants' food choices, the role of their parents in their diet, and healthy body-related concerns among their peers., Analyses: Verbatim transcripts were coded in NVivo 12 on the basis of specificity, extensiveness, and frequency. Themes emerged from group dialogue, detailed conversations, and predominant topics of discussion, and aligned with ecological systems theory., Results: Participants referred to factors influencing Latinx seventh-grade students' eating behaviors at the individual, family, household, and school levels. At the individual level, participants described their eating as unhealthy and perceived it as determined by taste, convenience, ease of preparation, and home availability. Participants expressed concerns about diabetes because of their body weight and family history, and identified those concerns as reasons for acceptance of healthy foods and the desire for parents to model healthy eating behaviors. Family-level factors perceived as influencing dietary behaviors included the role of parents as providers of food and models of unhealthy eating, budget constraints, and availability (or lack thereof) of healthy foods at home. Similarly, the identified school-level factors aligned with availability and quality of foods in that environment., Conclusions: Family- and household-related factors emerged as important influences on seventh-grade students' dietary behaviors. Future diet interventions should incorporate strategies targeting these multiple-level factors that influence dietary intake for Latinx youth and that address the concerns related to disease risk., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Artisanal and small-scale gold mining (ASGM) is the largest anthropogenic source of mercury emissions globally. Concern over mercury pollution increases due to its long-term impacts on human health and aquatic and terrestrial ecosystems. Using a participatory research methodology, we gathered social and behavioral information regarding daily practices and water usage by an ASGM community in Suárez, Colombia. Based on this information, we identified 18 sampling sites of water sources commonly used by the community. The samples were analyzed for total mercury, total coliforms, pH, electrical conductivity, and total dissolved oxygen. Physicochemical and microbiological parameters from the water assessment were compared with the drinking water thresholds set by the Colombian regulatory agencies, the EPA, and the WHO. Our results showed that the majority of the samples do not meet one or more quality and safety standards. On average, the sampling sites showed total mercury levels below the regulatory limits; however, the data had considerable variability, and in many cases, individual observations fell above the maximum concentration limit for drinking water. We discuss these results within the larger framework of the regulatory gaps for human and environmental protection in ASGM contexts. The total lack of water, sanitation, and hygiene infrastructure, combined with the long-term consumption of sublethal doses of mercury and other water contaminants, constitutes a significant threat to the well-being of communities and territories that necessitates further research and intervention by institutional authorities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Adjustment of key parameters of electrical stunning of pigs is necessary to better respect animal welfare and avoid impairments of meat quality. In the present study, we analysed the effect of genetic line, stunning program and genetic line × stunning program interactions on stunning effectiveness, carcass and meat quality traits in 10,338 pigs from five different genetic lines in a German slaughterhouse using electrical stunning (two-cycle method head/heart current). Genetic line, stunning program and its interaction significantly influenced stunning effectiveness and pH in the semimembranosus muscle. Backup stunning rates ranged from 1.59 to 5.01% in the five genetic lines, and were significantly decreased (2.85%) in program 1 using a current of 1.3 to 1.35 A, 800 Hz and 1 s for the head-cycle compared to program 2 (4.73%) with 1.8 A, 100 Hz and 4.5 s. We suggest to consider genetic line × stunning program interactions when adjusting officially defined stunning parameters for head-heart electrical stunning., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA). THA-derived hip bones serve as a major source of healthy hematopoietic cells in experimental hematology. We prospectively investigated frequency and clinical associations of CH in 200 patients without known hematologic disease who were undergoing THA. Prevalence of CH was 50%, including 77 patients with CH of indeterminate potential (CHIP, defined as somatic variant allele frequencies [VAFs] ≥2%), and 23 patients harboring CH with lower mutation burden (VAF, 1% to 2%). Most commonly mutated genes were DNMT3A (29.5%), TET2 (15.0%), and ASXL1 (3.5%). CHIP is significantly associated with lower hemoglobin, higher mean corpuscular volume, previous or present malignant disease, and CVD. Strikingly, we observed a previously unreported association of CHIP with autoimmune diseases (AIDs; multivariable adjusted odds ratio, 6.6; 95% confidence interval, 1.7-30; P = .0081). These findings underscore the association between CH and inflammatory diseases. Our results have considerable relevance for managing patients with OA and AIDs or mild anemia and question the use of hip bone-derived cells as healthy experimental controls., (© 2021 by The American Society of Hematology.)

Purpose: Early detection and treatment can prevent irreversible blindness from diabetic retinopathy (DR), which is the leading cause of visual impairment among working-aged adults worldwide. Some 80% of affected persons live in low- and middle-income countries, yet lack of resources has largely prevented DR screening implementation in these world regions. Smartphone-based fundus imaging (SBFI) allows for low-cost mobile fundus examination using an adapter on a smartphone; however, key aspects such as image quality, diagnostic accuracy, and comparability of different approaches have not been systematically assessed to date., Design: Evaluation of diagnostic technology., Participants: A total of 381 eyes of 193 patients with diabetes were recruited at outreach eye clinics in South India., Methods: We compared 4 technically different approaches of SBFI (3 approaches based on direct and 1 approach based on indirect ophthalmoscopy) in terms of image quality and diagnostic accuracy for DR screening., Main Outcome Measures: Image quality (sharpness/focus, reflex artifacts, contrast, and illumination), field-of-view, examination time, and diagnostic accuracy for DR screening were analyzed against conventional fundus photography and clinical examination., Results: Smartphone-based fundus imaging based on indirect ophthalmoscopy yielded the best image quality (P < 0.01), the largest field-of-view, and the longest examination time (111 vs. 68-86 seconds, P < 0.0001). Agreement with the reference standard (Cohen's kappa 0.868) and sensitivity/specificity to detect DR were highest for the indirect SBFI approach (0.79/0.99 for any DR and 1.0/1.0 for severe DR, 0.79/1.0 for diabetic maculopathy)., Conclusions: Smartphone-based fundus imaging can meet DR screening requirements in an outreach setting; however, not all devices are suitable in terms of image quality and diagnostic accuracy. Smartphone-based fundus imaging might aid in alleviating the burden of DR screening in low- and middle-income countries, and these results will allow for a better selection of SBFI devices in field trials for DR screening., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Biophysical techniques that enable the screening and identification of weak affinity fragments against a target protein are at the heart of Fragment Based Drug Design approaches. In the case of membrane proteins, the crucial criteria for fragment screening are low protein consumption, unbiased conformational states and rapidity because of the difficulties in obtaining sufficient amounts of stable and functionally folded proteins. Here we show for the first time that lipid-nanodisc systems (membrane-mimicking environment) and miniaturized affinity chromatography can be combined to identify specific small molecule ligands that bind to an integral membrane protein. The approach was exemplified using the AA 2A R GPCR. Home-made affinity nano-columns modified with nanodiscs-embedded AA 2A R (only about 1 μg of protein per column) were fully characterized by frontal chromatographic experiments. This method allows (i) to distinguish specific and unspecific ligand/receptor interactions, (ii) to assess dissociation constants, (iii) to identify the binding pocket of uncharacterized ligands using a reference compound (whose binding site is known) with competition experiments. Weak affinity ligands with Kd in the low to high micromolar range can be detected. At last, the applicability of this method was demonstrated with 6 fragments recently identified as ligands or non-ligands of AA 2A R., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Latinx adolescents are at higher risk for chronic diseases relative to adolescents of other ethnic groups, in part because of their lack of adherence to diet recommendations and their higher rates of substance use. Given the proximal influence of family factors during the developmental stage of adolescence, parenting interventions may be an effective way to promote healthy nutrition and substance use prevention simultaneously. This article describes the design and theoretical rationale of a study assessing the effects of Families Preparing the New Generation Plus (FPNG Plus), a 10-week culturally-tailored nutrition and substance use prevention parenting program, on diet and substance use outcomes among Latinx middle school students (6th-8th grade). The 3-arm cluster randomized controlled trial compares FPNG Plus (substance use prevention and healthy nutrition), FPNG (substance use prevention only), and a comparison condition (focusing on academic success) in 1494 parent-child dyads from 18 schools, randomized at the school level. Adolescents and parents will complete surveys pre- and post-intervention, and 16-weeks after program participation, regarding diet behaviors, substance use, and parenting practices. A random subsample of 126 dyads (42 from each program), will participate in additional data collection to assess the home food environment, detailed dietary intake (via two 24-h recalls), and provide biomarkers of cardiometabolic risk (blood pressure, total cholesterol and HbA1c). If successful, this study will provide evidence contributing to helping Latinx parents assist their adolescent children develop and maintain long-lasting positive lifestyle behaviors in order to prevent concurrent substance use and diet-related chronic diseases., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exaggerated attentional biases toward specific elements of the environment contribute to the maintenance of several psychiatric conditions, such as biases to threatening faces in social anxiety. Although recent literature indicates that attentional bias modification may constitute an effective approach for psychiatric remediation, the underlying neurophysiological mechanisms remain unclear. We addressed this question by recording EEG in 24 healthy participants performing a modified dot-probe task in which pairs of neutral cues (colored shapes) were replaced by probe stimuli requiring a discrimination judgment. To induce an attentional bias toward or away from the cues, the probes were systematically presented either at the same or at the opposite position of a specific cue color. This paradigm enabled participants to spontaneously develop biases to initially unbiased, neutral cues, as measured by the response speed to the probe presented after the cues. Behavioral result indicated that the ABM procedure induced approach and avoidance biases. The influence of ABM on inhibitory control was assessed in a separated Go/NoGo task: changes in AB did not influence participants' capacity to inhibit their responses to the cues. Attentional bias modification was associated with a topographic modulation of event-related potentials already 50-84 ms following the onset of the cues. Statistical analyses of distributed electrical source estimations revealed that the development of attentional biases was associated with decreased activity in the left temporo-parieto-occipital junction. These findings suggest that attentional bias modification affects early sensory processing phases related to the extraction of information based on stimulus saliency., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The clinical and prognostic relevance of many recently identified driver gene mutations in adult acute myeloid leukemia (AML) is poorly defined. We sequenced the coding regions or hotspot areas of 68 recurrently mutated genes in a cohort of 664 patients aged 18 to 86 years treated on 2 phase 3 trials of the German AML Cooperative Group (AMLCG). The median number of 4 mutations per patient varied according to cytogenetic subgroup, age, and history of previous hematologic disorder or antineoplastic therapy. We found patterns of significantly comutated driver genes suggesting functional synergism. Conversely, we identified 8 virtually nonoverlapping patient subgroups, jointly comprising 78% of AML patients, that are defined by mutually exclusive genetic alterations. These subgroups, likely representing distinct underlying pathways of leukemogenesis, show widely divergent outcomes. Furthermore, we provide detailed information on associations between gene mutations, clinical patient characteristics, and therapeutic outcomes in this large cohort of uniformly treated AML patients. In multivariate analyses including a comprehensive set of molecular and clinical variables, we identified DNMT3A and RUNX1 mutations as important predictors of shorter overall survival (OS) in AML patients <60 years, and particularly in those with intermediate-risk cytogenetics. NPM1 mutations in the absence of FLT3-ITD, mutated TP53, and biallelic CEBPA mutations were identified as important molecular prognosticators of OS irrespective of patient age. In summary, our study provides a comprehensive overview of the spectrum, clinical associations, and prognostic relevance of recurrent driver gene mutations in a large cohort representing a broad spectrum and age range of intensively treated AML patients., (© 2016 by The American Society of Hematology.)

In acute myeloid leukemia (AML), isolated trisomy 13 (AML+13) is a rare chromosomal abnormality whose prognostic relevance is poorly characterized. We analyzed the clinical course of 34 AML+13 patients enrolled in the German AMLCG-1999 and SAL trials and performed exome sequencing, targeted candidate gene sequencing and gene expression profiling. Relapse-free (RFS) and overall survival (OS) of AML+13 patients were inferior compared to other ELN Intermediate-II patients (n=855) (median RFS, 7.8 vs 14.1 months, P = .006; median OS 9.3 vs. 14.8 months, P = .004). Besides the known high frequency of RUNX1 mutations (75%), we identified mutations in spliceosome components in 88%, including SRSF2 codon 95 mutations in 81%. Recurring mutations were detected in ASXL1 (44%) and BCOR (25%). Two patients carried mutations in CEBPZ, suggesting that CEBPZ is a novel recurrently mutated gene in AML. Gene expression analysis revealed a homogeneous expression profile including upregulation of FOXO1 and FLT3 and downregulation of SPRY2. This is the most comprehensive clinical and biological characterization of AML+13 to date, and reveals a striking clustering of lesions in a few genes, defining AML+13 as a genetically homogeneous subgroup with alterations in a few critical cellular pathways. Clinicaltrials.gov identifiers: AMLCG-1999: NCT00266136; AML96: NCT00180115; AML2003: NCT00180102; and AML60+: NCT00893373., (© 2014 by The American Society of Hematology.)

Background: The objective of the study was to evaluate completion rates and toxic effects of an i.p. chemotherapy regimen in a cross-section of nonselected patients with ovarian cancer (OC)., Patients and Methods: All patients with stage IIIC OC consecutively operated at our institution from January 2006 to December 2007 were prospectively collected and analyzed., Results: Eighty-nine patients with stage IIIC OC optimally debulked were evaluated for this study. An i.p. port was primarily placed in 53 of 89 (60%), and i.p. chemotherapy was recommended in 55 patients. Reasons for not recommending i.p. chemotherapy in patients optimally debulked included postoperative complications (n = 7: 8%), poor nutritional/functional status (n = 5: 6%), and extensive surgery including bowel resection (n = 9: 10%). Thirty-three patients (33/55: 60%) recommended to receive i.p. chemotherapy-initiated i.p. treatment. Fifty-two percent of those beginning i.p. therapy (17/33) received three or more cycles with 36% (12/33) successfully completing six cycles. Reasons for discontinuation included grade 3-4 nephrotoxicity in 3 of 21 (14%), febrile neutropenia/sepsis in 3 of 21 (14%), port infection or malfunction in 8 of 21 (38%)., Conclusions: The i.p. chemotherapy regimen used in a consecutive cohort of patients carries could be completed in only a small percentage of patients. Less toxic regimens with higher acceptability should be considered.

The reggies/flotillins were discovered as proteins upregulated during axon regeneration. Here, we show that expression of a trans-negative reggie-1/flotillin-2 deletion mutant, R1EA, which interferes with oligomerization of the reggies/flotillins, inhibited insulin-like growth factor (IGF)-induced neurite outgrowth in N2a neuroblastoma cells and impaired in vitro differentiation of primary rat hippocampal neurons. Cells expressing R1EA formed only short and broad membrane protrusions often with abnormally large growth cones. R1EA expression strongly perturbed the balanced activation of the Rho-family GTPases Rac1 and cdc42. Furthermore, focal adhesion kinase (FAK) activity was also enhanced by R1EA expression, while other signaling pathways like ERK1/2, PKC or PKB signaling were unaffected. These severe signaling defects were caused by an impaired recruitment of the reggie/flotillin-associated adaptor molecule CAP/ponsin to focal contacts at the plasma membrane. Thus, the reggies/flotillins are crucial for coordinated assembly of signaling complexes regulating cytoskeletal remodeling.

Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability.

In order to investigate the capability of an autochthonous bacterium to modulate the host's immune response against the indigenous microfiora, the immunogenicity of two selected bacterial species of the human gut was investigated in a gnotobiotic rat model. Germ-free (GF) rats were monoassociated with either Bifidobacterium (B.) adolescentis or Bacteroides (B.) thetaiotaomicron and the development of bacteria-specific IgG and IgA in serum and specific secretory IgA (sIgA) in feces of the animals were measured. Knowing the antibody levels in gnotobiotic rats induced by monoassociation, we subsequently diassociated two groups of rats in order to investigate the impact of B. adolescentis on the immune reaction against B. thetaiotaomicron. One group was diassociated simultaneously with B. adolescentis and B. thetaiotaomicron, the second group was diassociated with these bacteria in sequence. In contrast to B. thetaiotaomicron, B. adolescentis was not able to induce a systemic immune response in monoassociated animals as evident from serum IgG and IgA. However, both bacterial species challenged the mucosal immune system as indicated by an increase in sIgA in the feces. The specific immune response to B. thetaiotaomicron was significantly lower in diassociated animals than in animals monoassociated with B. thetaiotaomicron. This effect was more pronounced in the rats, that had been associated sequentially. The presence of B. adolescentis down-regulated the humoral immunity to B. thetaiotaomicron.

The anticarcinogen conjugated linoleic acid (CLA) is a product of bacterial activity that isomerizes linoleic acid (LA) in the rumen of herbivores. Therefore, fatty dairy products in the human diet are enriched with CLA. Although bacteria capable of in vitro LA conjugation were detected in the human intestinal tract, CLA synthesis from dietary sunflower seed oil was not observed in gnotobiotic rats associated with these intestinal bacteria. The objective of the study was to investigate variables that affect LA conjugation. In vitro, LA conjugation was strongly inhibited by glucose and other substrates. Concentrations of 1.5 mmol glucose/L inhibited LA conjugation by 50%. Methyl-alpha-D-glucoside was a less effective inhibitor than glucose, and 2-deoxy-D-glucose did not inhibit LA conjugation at all. To analyze the concentration of carbohydrates in intestinal contents, the LA-conjugating bacterial mixed culture and human fecal microorganisms were introduced into germ-free rats. Samples of feces and cecum and colon contents of both groups exhibited in vitro LA-conjugating activity. Rats associated with human intestinal microorganisms contained 5.7 +/- 1. 3 mmol glucose/L in the cecal contents and 6.6 +/- 1.0 mmol glucose/L in the colonic contents. Rats associated with CLA-producing bacterial culture contained 3.4 +/- 1.3 mmol glucose/L in the cecal contents and 4.2 +/- 1.0 mmol glucose/L in the colonic contents. These values are within a range that may explain the observed inhibition of LA conjugation in vivo.

Women at high risk for the development of breast cancer have several options open to them including increased cancer surveillance, prophylactic mastectomy and/or oophorectomy, and chemoprevention. We consider high-risk women to be those with known BRCA mutations or a strong family history characterized by multiple relatives with breast cancer, early age at diagnosis, and in some families, ovarian cancer. We present existing data regarding prophylactic surgery for these women. Essentially, a woman at high risk for breast cancer may choose to undergo bilateral prophylactic mastectomy, with or without reconstruction. For patients who have a known breast cancer, contralateral mastectomy is also an option. Finally, for women in families with a strong incidence of ovarian cancer, prophylactic oophorectomy can be considered.

Pectin is a soluble indigestible polysaccharide that stimulates cecal polyamine formation in rats. Bacteroides and fusobacteria, two numerically dominant bacterial population groups in the large intestine, were found to synthesize in vitro high amounts of spermidine and putrescine. The purpose of this study was to elucidate the effect of pectin on the polyamine production by defined bacterial species in vivo. Germfree male Wistar rats (n = 18) were randomly assigned to one of three treatments: (i) monoassociation with Bacteroides thetaiotaomicron + fiber-free diet; (ii) diassociation with B. thetaiotaomicron + Fusobacterium varium + fiber-free diet or (iii) diassociation with B. thetaiotaomicron + F. varium + fiber-free diet + 10% pectin. The cecal contents of monoassociated rats fed fiber-free diet contained large amounts (1.51+/-0.21 micromol/dry total cecum content) of spermidine which was the major polyamine. The cecum of diassociated rats fed the fiber-free diet contained even higher concentrations of spermidine (2.53+/-0.21 micromol/dry total cecum content) and also putrescine, which was now the dominant polyamine (putrescine 0.32+/-0.28 vs. 3.01+/-0.28 micromol/dry total cecum content; monoassociation vs. diassociation). Pectin consumption by diassociated rats led to an additional increase in the cecal concentrations of all polyamines: putrescine, spermidine and spermine were 40, 37 and 100%, respectively, higher in the diassociated rats consuming the pectin diet than in those consuming the pectin-free diet. Since the microbial counts in the cecum did not differ in the diassociated treatment groups, the elevated concentrations of polyamines observed in the pectin group must have been due to stimulated bacterial polyamine synthesis. The decline of individual polyamines from cecum to feces detected at the end of the study in all treatment groups and the high microbial counts in the cecum and in feces suggest that bacterial polyamines are absorbed in cecum and colon. Pectin stimulates intestinal microbes to synthesize large amounts of polyamines which may be utilized by the host.

Purpose: We updated an earlier study in this community from 1945-1974 in order to assess trends in the incidence of, risk factors for, and survival from endometrial cancer in 1975-1991., Methods: Incidence rates were based on all new cases of endometrial cancer diagnosed among Olmsted County, Minnesota, women during the years 1975-1991, with the population denominator from decennial census data. Risk factors were assessed with conditional logistic regression comparing the incidence cases to age- and gender-matched controls with intact uteri seen the same year the case was diagnosed. Survival was assessed using the Kaplan-Meier method., Results: The incidence of endometrial cancer (age-adjusted to 1970 United States total) in 1975-1991 was 14.3 per 100,000 person-years, which is slightly increased from 1965-74. The rate was 21.7 per 100,000 person-years after adjustment for hysterectomy prevalence. As in the previous study, conjugated estrogen use for six months or more (odds ratio [OR] 2.71; 95% confidence interval [CI] 1.14-6.46) and body mass index (OR 1.06; 95% CI 1.01-1.11) increased the risk of endometrial cancer. The five-year relative survival rate (82%) was not improved over the earlier study., Conclusions: A small increase in endometrial cancer incidence was linked to the same risk factors identified in an earlier study in this community. No improvement in survival was seen.

Purpose: To determine trends in incidence and survival between 1935 and 1991 and to evaluate risk factors for ovarian cancer among Olmsted County, Minnesota women., Methods: All newly diagnosed cases of ovarian cancer among Olmsted County women in 1975-1991 were identified using the medical records linkage system of the Rochester Epidemiology Project. In order to assess trends, incidence rates in the subset of Rochester women were compared with Rochester rates for 1935-1974. Survival was evaluated by the Kaplan-Meier product-limit method. A case-control analysis of risk factors compared Olmsted County women with invasive epithelial ovarian cancer and an age-matched group of women from the community by logistic regression., Results: Altogether, 129 Olmsted County women were newly diagnosed with ovarian cancer in 1975-1991. The age-adjusted (to 1970 United States whites) incidence rate was 22.5 per 100,000 person-years. Median survival from initial diagnosis was 3.7 years. Compared to an equal number of controls, the 103 women with invasive epithelial disease were more likely to be nulliparous (odds ratio [OR] 1.9; 95% CI 0.95-3.9) but less likely to have a history of thyroid disease (OR 0.4; 95% CI 0.2-0.8), hypertension (OR 0.4; 95% CI 0.1-0.9) or nonsteroidal estrogen use (OR 0.5; 95% CI 0.2-0.9). Prior hysterectomy (OR 0.5; 95% CI 0.2-0.9) and unilateral oophorectomy (OR 0.2; 95% CI 0.04-0.7) were also associated with reduced risk., Conclusion: The incidence of ovarian cancer in this community in 1975-1991 was little changed from rates 20 years earlier. There has been some improvement in survival from ovarian cancer in this population compared to 1935-1974, but still less than 50% survive for 5 years. Prior hysterectomy and unilateral oophorectomy appear protective for ovarian cancer.

Conjugated linoleic acid (CLA) is produced from linoleic acid (LA) by bacteria in the rumen of herbivores. CLA enters the human diet mainly via milk fat and fatty beef; it acts as an effective anticarcinogen and exhibits other important physiological effects. The objective of the current study was to investigate the capability of a LA-conjugating bacterial community isolated from a human volunteer and associated with germ-free rats to supply the host with CLA. Gnotobiotic rats were fed a diet enriched with esterified LA in the form of sunflower-seed oil. The control group was fed the same diet and remained germ-free. Bacterial cell counts, in vitro LA-conjugation activities, and CLA concentration in feces and in the contents of various intestinal segments were determined. After 10 wk, various tissues were analyzed for CLA concentrations. LA-conjugation activity was found only in feces, cecum and colon content samples from associated rats, but CLA accumulation in various body tissues did not differ significantly between the two groups. The ratio of CLA to LA in feces and in cecal and colonic contents did not differ between groups, indicating that the microorganisms in the cecum and the colon do not synthesize substantial amounts of CLA in vivo and therefore, do not contribute to the CLA supplementation of the host.

Cell proliferation requires calmodulin, a protein that regulates calcium-dependent enzymes involved in signal transduction pathways in eukaryotic cells. Calmodulin-like protein (CLP) is found in certain epithelial cell types, including normal breast epithelium, and, although it closely resembles calmodulin in amino acid sequence, CLP interacts with different proteins than does calmodulin. The observation that CLP mRNA expression is dramatically reduced in transformed breast epithelial cells led to two hypotheses: (1) CLP helps to maintain the differentiated state in epithelial cells; and (2) downregulation of CLP accompanies malignant transformation of breast epithelial cells. The objective of this study was to determine if the expression of CLP in human breast cancer specimens is reduced in comparison to its expression in normal breast tissue. Eighty human breast cancer biopsy specimens were analyzed immunohistochemically for CLP expression by using a polyclonal rabbit antihuman CLP antibody. CLP expression was reduced in 79% to 88% of the invasive ductal carcinoma and lobular carcinoma specimens and in a similar fraction of the ductal carcinoma in-situ specimens, compared with normal breast specimens. None of the breast cancer specimens showed an increase in CLP expression. These findings support the hypotheses that CLP behaves as a functional tumor suppressor protein and is downregulated early in breast cancer progression.

Pain is a central factor affecting quality of life for the cancer patient. This descriptive study was designed to explore the relationship between pain and several factors affecting quality of life. The factors explored included physical and social functioning, emotional health, and spiritual commitment in women with recurrent breast or gynecologic cancer. Pain frequency, amount, and interference with activities were found to correlate more strongly with objective measures of quality of life (i.e., physical and social functioning) than subjective measures (i.e., psychological or spiritual dimensions).

A 52-year-old woman was diagnosed with a cardiac tumor by transesophageal echocardiography and magnetic resonance imaging. An intraoperative biopsy indicated the mass was low-grade endometrial stromal sarcoma. Successful tumor removal from the heart and inferior vena cava was accomplished with the use of hypothermic circulatory arrest. The chronically occluded infrarenal portion of the inferior vena cava was transected. The patient has no evidence of recurrent disease after a follow-up of 18 months and has no significant restriction in her daily activities.

Karyotype information on ovarian carcinomas has been limited because the tumors are often difficult to culture and the resultant metaphases can have complex numerical and structural chromosomal anomalies. Fluorescent in situ hybridization is a rapid method of determining centromere copy number in metaphase cells and interphase nuclei. Fluorescent in situ hybridization was used to determine the numerical centromere complement of chromosomes X, 8, 12, and 17 and HER-2/neu gene amplification within interphase nuclei of 25 primary epithelial ovarian carcinomas. Touch preparations of the carcinomas were hybridized with two-color combinations of directly labeled alpha-satellite centromeric chromosome enumeration probes and a directly labeled HER-2/neu probe. Modal centromere copy numbers for each of the four chromosomes were used to determine numerical abnormalities relative to the flow cytometric DNA ploidy level for each tumor. Four cases were found to be normal with respect to the four chromosomes studied. In the remaining 21 cases a relative loss of chromosomes 17 (16 cases) and X (nine cases) and a relative gain of chromosomes 12 (10 cases) and 8 (nine cases) were the most common findings. In addition, the HER-2/neu gene was amplified in two of the 25 tumors. In conclusion, fluorescent in situ hybridization is an excellent method for rapid determination of numerical abnormalities and gene amplification in ovarian carcinomas.

A 60-year-old man with advanced seminoma was treated with four cycles of a cisplatin, etoposide and bleomycin. He then developed severe pulmonary toxicity with diffuse infiltrates as evidenced on a chest x-ray film. The room air PaO2 value was 32 mm Hg. The patient was treated with steroids and oxygen supplementation, including a high FIo2 for several days, and survived and eventually experienced marked improvement in his pulmonary status. Aggressive management of severe bleomycin-induced pneumonitis appears justified.

Two related but clearly different cDNA clones corresponding to elongation factor 1 alpha (EF-1 alpha) mRNAs were isolated from a Xenopus laevis gastrula-stage library. Whereas the nucleotide sequences of these two cDNAs differ within the coding region at 49 out of 1386 positions (3.5%), the derived amino acid sequences are completely identical, thereby indicating a substantial evolutionary constraint on this translation factor. Southern-blot analysis of genomic DNA suggests that, besides the two closely related EF-1 alpha genes investigated in this study, other more-distantly related genes may exist in the X. laevis genome. Transcription of EF-1 alpha genes during oogenesis and embryonic development was studied by Northern-blot analysis and by in situ hybridizations. A high amount of EF-1 alpha mRNA was detected in previtellogenic oocytes. At later stages of embryonic development, EF-1 alpha mRNA was found to be accumulated in translationally active tissues.

Numerous important issues in breast cancer were debated this past year. Several examples include: the role of screening mammography in women aged 40-49, the management of carcinoma in situ, adjuvant chemotherapy for postmenopausal node-positive women, adjuvant therapy for node-negative women, the primary management of elderly women with breast cancer, the use of a composite of prognostic factors for better predictive power and measures to improve the therapeutic index of the anthracyclines.

Platelets of reserpinized rabbits, incubated in buffer containing tritiated 5-hydroxytryptamine (3H-5HT), have the ability to convert 3H-5HT into labeled compound(s) extractable with alkaline-chloroform. The bulk of the chloroform-extractable radioactivity showed a Rf value similar to authentic melatonin on silicagel thin-layer chromatography. The labelled product eluted with ethanol from the silicagel area where melatonin was suspected to reside was identified as melatonin by mass spectrometry and radioimmunoassay. Our in vitro experiments demonstrate that rabbit platelets are capable of converting 5-HT into melatonin apparently because they possess the enzymatic equipment necessary for this biosynthesis i.e. serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase.

Plasma and urinary melatonin, testosterone and luteinizing hormones were radioimmunologically assayed in 26 male babies during the first year of life. The results show that plasma melatonin levels are low during the phase of postnatal elevation of testosterone and luteinizing hormones. They subsequently increase when testicular activity decreases. Urinary elimination of melatonin does not vary during this period, suggesting the existence of variations in the synthesis or utilization of melatonin.

A technique for the determination of free and esterified plasma cholesterol by gas-liquid chromatography is proposed as a reference method. After a critical examination of all the stages to prove its validity, the method is compared to the usual techniques. Such a comparison confirms that colorimetric methods are more accurate after a lipidic extraction and with a purification step by liquid-solid chromatography.

Urinary melatonin variation in humans were demonstrated to be a function of age. A radioimmunological assay was used. The values obtained, expressed as nmol x 24 h-1 x kg-1, progressively decreased from birth onwards, with a more accentuated and momentary inflection at the moment of the genital crisis in newborns and at puberty. The results obtained concern only melatonin and not its metabolites, as a result of the high specificity of the antibodies employed.

The gas-liquid chromatographic measurement of urinary creatinine described in this paper employs methylation, the use of a diethylene glycol succinate stationary phase, an internal L-hydroxyproline standard and a temperature of 180 degrees C. The technique, which is specific and reproducible, is shown to be a reference method providing more precise and reliable results than a conventional colorimetric method. In addition, it can be used as a routine method because of its simplicity.

Affinity chromatography purification was combined with a radioimmunoassay for 'Tamm-Horsfall-like' glycoprotein. This enabled serum concentrations to be established and to demonstrate its presence in cerebrospinal fluid for the first time. This assay method used in different circumstances suggests a multifocal synthesis. Nevertheless, urinary Tamm-Horsfall glycoprotein so far must be distinguished from the serum or cerebrospinal fluid Tamm-Horsfall-like glycoprotein.

Anti-melatonin antibodies of high titer and good sensitivity were obtained by coupling melatonin to bovine serum albumin with formaldehyde and by immunizing rabbits with multifocal intra-dermal injections. A systematic study of cross-reactions with 14 compounds (indole, aromatic and imidazole derivatives) showed that the antibody had a high specificity for melatonin, low reactivities with 6-hydroxymelatonin and N-acetylserotonin and no detectable reactivity with 12 other derivatives. The roles of the indole nucleus and the side chain in the determination of the antigenic properties of the molecule are discussed.

An original method for the quantitative determination of plasmatic urea by gas-liquid chromatography (GLC) is described. It is based upon the transformation of urea into urethane by alcoholic deamination in a warm and strictly anhydrous medium. Compared with the two other usual methods (enzymatic and colorimetric), the GLC technique is extremely reliable and specific, and can easily be adapted to biological fluids.

The monosaccharides of proteic samples liberated by methanolysis and submitted to trimethylsilylation by the trimethylsilylimidazole (TSIM) are determined by gas-liquid chromatography. The neutral sugars are detected in simple flame ionization (FID) and the amino sugars identified separatively by the use of a thermoionic detector (TID) which responds selectively to nitrogenous and phosphorated compounds. The method described has been tested on standard mixtures of monosaccharides and on a well known glycoprotein : the uromucoid. Then it has been applied to a pyroglobulin IgM (mu2, chi2).