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Our objective was to determine the factors associated with the successful maturation of arteriovenous fistulas during hemodialysis.

The fundamental steps in high-grade serous ovarian cancer (HGSOC) initiation are unclear, thus providing critical barriers to the development of prevention or early detection strategies for this deadly disease. Increasing evidence demonstrates most HGSOC starts in the fallopian tube epithelium (FTE). Current models propose HGSOC initiates when FTE cells acquire increasing numbers of mutations allowing cells to evolve into serous tubal intraepithelial carcinoma (STIC) precursors and then to full blown cancer. Here we report that epigenetically altered mesenchymal stem cells (termed high risk MSC-hrMSCs) can be detected prior to the formation of ovarian cancer precursor lesions. These hrMSCs drive DNA damage in the form of DNA double strand breaks in FTE cells while also promoting the survival of FTE cells in the face of DNA damage. Indicating the hrMSC may actually drive cancer initiation, we find hrMSCs induce full malignant transformation of otherwise healthy, primary FTE resulting in metastatic cancer in vivo . Further supporting a role for hrMSCs in cancer initiation in humans, we demonstrate that hrMSCs are highly enriched in BRCA1/2 mutation carriers and increase with age. Combined these findings indicate that hrMSCs may incite ovarian cancer initiation. These findings have important implications for ovarian cancer detection and prevention.

The present study sought to expand upon prior investigations of the relationship between post-exercise heart rate recovery (HRR) and cardiovagal resting-reactivity modulation. HRR from 1st to 5th min after maximal exercise test was correlated with a cardiovagal index of heart rate variability (SD1) at resting (supine and orthostatic positions) and its reactivity after the orthostatic stress test in 34 healthy women. Statistical analysis employed non-parametric tests with a p-value set at 5%. HRR, ∆%HRR, and coefficient of HRR (CHRR) at the 3rd and 5th min correlated with SD1 and SD1 n (normalized units) in the supine position (r s  = 0.36 to 0.47; p =  < 0.01). From the 1st to 5th min, HRR, ∆%HRR, and CHRR correlated with SD1 and SD1 n in the orthostatic position (r s  = 0.29 to 0.47; p =  ≤ 0.01 to 0.05), except for HRR at 5th min with SD1 n (p = 0.06). Following the orthostatic stress test, HRR at 3rd and HRR, %∆HRR at 5th min correlated with ∆absSD1 (r s  = 0.28 to 0.35; p = 0.02 to 0.05). All HRR measurements at 1st min correlated with ∆absSD1 n (r s  = 0.32 to 0.38; p = 0.01 to 0.03), and the CHRR at 1st min correlated with ∆%SD1(r s  = 0.37; p = 0.01). After the sample was divided into high and low cardiovagal modulation subgroups, the subgroup with high modulation at rest (supine and orthostatic) and higher cardiovagal reactivity (reduction) showed faster HRR (p =  ≤ 0.01 to 0.05; ES:0.37 to 0.50). HRR throughout the 1st to 5th min positively correlates with cardiovagal modulation in the orthostatic position, and the 3rd and 5th min positively correlate with cardiovagal modulation in both postures at rest. Faster HRR following the maximal exercise test is associated with high resting-reactivity cardiovagal modulation in healthy women., (© 2024. The Author(s).)

The ability of cancer cells to detach from the primary site and metastasize is the main cause of cancer- related death among all cancer types. Epithelial-to-mesenchymal transition (EMT) is the first event of the metastatic cascade, resulting in the loss of cell-cell adhesion and the acquisition of motile and stem-like phenotypes. A critical modulator of EMT in cancer cells is the stromal tumor microenvironment (TME), which can promote the acquisition of a mesenchymal phenotype through direct interaction with cancer cells or changes to the broader microenvironment. In this review, we will explore the role of stromal cells in modulating cancer cell EMT, with particular emphasis on the function of mesenchymal stromal/stem cells (MSCs) through the activation of EMT-inducing pathways, extra cellular matrix (ECM) remodeling, immune cell alteration, and metabolic rewiring.

Athletic shoes that induce dorsiflexion in standing can improve jump height compared to traditional athletic shoes that induce plantarflexion, but it is unknown if dorsiflexion shoes (DF) also affect landing biomechanics associated with lower extremity injury risk. Thus, the purpose of this study was to investigate if DF adversely affect landing mechanics related to patellofemoral pain and anterior cruciate ligament injury risk compared to neutral (NT) and plantarflexion (PF) shoes. Sixteen females (21.65 ± 4.7 years, 63.69 ± 14.3 kg, 1.60 ± 0.05 m) performed three maximum vertical countermovement jumps in DF (-1.5°), NT (0°) and PF (8°) shoes as 3D kinetics and kinematics were recorded. One-way repeated-measures ANOVAs revealed peak vertical ground reaction force, knee abduction moment and total energy absorption were similar between conditions. At the knee, peak flexion and joint displacement were lower in DF and NT, while relative energy absorption was greater in PF (all p  < .01). Conversely, relative ankle energy absorption was greater in DF and NT compared to PF ( p  < .01). Both DF and NT induce landing patterns that may increase strain on passive structures in the knee, emphasising the need for landing mechanics to be considered when testing footwear as gains in performance could come at the cost of injury risk.

The effect of resting heart rate (RHR) on the heart rate (HR) dynamics and parasympathetic modulation at rest, exercise, and recovery remain to be clarified. This study compares HR and parasympathetic responses at rest, during submaximal exercise testing and recovery in young, physically active men with different RHR average values. HR and parasympathetic responses were compared between two groups: bradycardia group-RHR < 60 bpm (BG, n = 20) and normocardia group-RHR ≥ 60 ≤ 100 bpm (NG, n = 20). A Polar RS800® was used to record the RR-interval series and HR at rest in the supine position, following the postural change (from supine to orthostatic position) and in the orthostatic position for 5 minutes, as well as during and after a submaximal exercise testing. Statistical analysis employed the MANOVA, Mann-Whitney, and Simple Linear regression test with a two-tailed p-value set at ≤ 0.05. BG at rest showed lower HR in the orthostatic position, higher parasympathetic activity in the supine and orthostatic positions, and higher parasympathetic reactivity than NG (p ≤ 0.01) after the postural change. BG before exercise showed lower HR and higher values of the chronotropic reserve and parasympathetic withdrawal than NG (p ≤ 0.01) throughout the exercise. Following the exercise, BG showed higher values of HR recovery (HRR) and parasympathetic reactivation in the 3rd and 5th minutes of recovery than NG (p ≤ 0.01). Lastly, the RHR can explain the variance of the HR at rest, during exercise testing, and recovery from 11 to 48%. We concluded that BG (RHR < 60 bpm) showed higher chronotropic and parasympathetic modulation at rest, higher chronotropic reserve, parasympathetic withdrawal during the submaximal exercise test, and faster HRR and parasympathetic reactivation after effort in young physically active men., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Garcia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Understanding if roller massage prior to a run can mitigate fatigue-related decrements in muscle force production during prolonged running is important because of the association between fatigue and running-related injury., Objective: The authors investigated whether a bout of roller massage prior to running would (1) mitigate fatigue-related increases in vertical average load rate and free moment of the ground reaction force of running and (2) mitigate decreases in maximal countermovement jump height., Design: Repeated-measures study., Setting: Laboratory., Participants: A total of 14 recreational endurance athletes (11 men and 3 women) volunteered for the study., Interventions: A 12.5-minute foam roller protocol for the lower extremities and a fatiguing 30-minute treadmill run., Main Outcome Measures: Vertical average load rate, free moment, and maximal jump height before (PRE) and after (POST) the fatiguing treadmill run on separate experimental days: once where participants sat quietly prior to the fatiguing run (REST) and another where the foam roller protocol was performed prior to the run (ROLL)., Results: A 2-way multiple analysis of variance found no significant differences in vertical average load rate, free moment, and jump height between PRE/POST times in both REST/ROLL conditions., Conclusions: The authors concluded that recreational endurance athletes maintain running mechanics and jump performance after a fatiguing run regardless of prerun roller massage and may not rely on prerun roller massage as a form of injury prevention.

The aim of this study was to assess the efficacy of imazamox for control of S. molesta and to assess the effects of plant decomposition on environmental indicators after application of this herbicide in microcosm conditions. The following rates were used: 600, 700, 800 and 900 g ai ha -1 and spray volume 50 L ha -1 . Control efficacy was determined as the percentage (from 0 to 100%) of visible injury symptoms in the plants, biochemical and chemical oxygen demand (BOD 5 and COD), water quality variables, chlorophyll a and pheophytin a at 0, 7, 15, 30, 45 and 60 days after application (DAA) and fresh and dry biomass at 60 DAA. Imazamox was effective in controlling 94% of S. molesta with 900 g ai ha -1 ; it reduced 95% of fresh weight and 92% of dry weight of plant at 60 DAA, and reduced chlorophyll a of the plants for all rates. For BOD 5 , there was an increase for all rates at 15, 30 and 45 DAA with restoration of the parameters at 60 DAA, and for COD, there was an increase at 60 DAA with 700 and 900 g ai ha -1 . For temperature, pH, dissolved oxygen and electrical conductivity, there was no significant effect after spraying. Imazamox was effective in controlling S. molesta with 900 g ai ha -1 without causing significant effects on the physical-chemical parameters of water quality.

This study aimed to assess, in a microcosm condition, the efficacy of electrostatic spraying of herbicide imazamox in the control of Salvinia molesta and the effects of decomposition of plant material on water quality. The herbicide rates used were 600, 700, 800, and 900 g ai ha -1 and spray volume of 50 L ha -1 in electrostatic application. Control effectiveness was assessed at 7, 15, 30, 45, and 60 days after application (DAA), expressed in percentage (0-100%) of visible injury symptoms in the plants, biochemical oxygen demand (BOD 5 ), chemical oxygen demand (COD), chlorophyll a and pheophytin a contents at 0, 7, 15, 30, 45, and 60 DAA, and fresh and dry biomass at 60 DAA. Imazamox was effective in controlling 63% of S. molesta with 900 g ai ha -1 in 45 DAA and 30% with 800 g ai ha -1 in 30 DAA, and reduced 82.3% and 17.5% of fresh weight and 62.6% and 9.3% of dry weight of plant at 60 DAA, respectively. The imazamox spray reduced chlorophyll a with all doses applied and increased BOD 5 in 45 DAA with 900 g ai ha -1 and COD in all assessment periods, but for temperature, dissolved oxygen, electrical conductivity, and pH, there was no significant effect after spraying. The herbicide imazamox reduced S. molesta plants with 900 g ai ha -1 , without causing significant effects on environmental indicators of water quality. Electrostatic spraying of herbicide can be used in management strategies of aquatic plants to reduce plant density in water bodies and maintain the colonization of plants at a level not harmful to the aquatic biota.

In areas where the zoonotic disease leptospirosis is endemic, reduced morbidity and mortality is strongly linked to quick initiation of renal replacement therapy., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2020 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Evidence from recent studies on animals and humans suggest that neural overflow from the primary sensory cortex (S1) to the primary motor cortex (M1) may play a critical role in motor control. However, it is unclear if whole-body maximal motor tasks are also governed by this mechanism. Maximum vertical squat jumps were performed by 15 young adults before cooling, then immediately following a 15-min cooling period using an ice-water bath for the foot soles, and finally immediately following a 15-min period of natural recovery from cooling. Jump heights were, on average, 3.1 cm lower immediately following cooling compared to before cooling ( p = 3.39 × 10 -8 ) and 1.9 cm lower following natural recovery from cooling ( p = 0.00124). The average vertical ground reaction force (vGRF) was also lower by 78.2 N in the condition immediately following cooling compared to before cooling ( p = 8.1 × 10 -5 ) and 56.7N lower following natural recovery from cooling ( p = 0.0043). The current study supports the S1-to-M1 overflow mechanism in a whole-body dynamic jump., (Copyright © 2020 Caminita, Garcia, Kwon, Miller and Shim.)

Chronic obstructive pulmonary disease (COPD) and asthma remain prevalent human lung diseases. Variability in epithelial and inflammatory components that results in pathologic heterogeneity complicates the development of treatments for these diseases. Early childhood infection with parainfluenza virus or respiratory syncytial virus is strongly associated with the development of asthma and COPD later in life, and exacerbations of these diseases correlate with the presence of viral RNA in the lung. Well-characterized animal models of postviral chronic lung diseases are necessary to study the underlying mechanisms of viral-related COPD and asthma and to develop appropriate therapies. In this study, we cross-analyzed chronic lung disease caused by infection with Sendai virus (SeV) or influenza A virus in mice. Differences were observed in lesion composition and inflammatory profiles between SeV- and influenza A virus-induced long-term lung disease. In addition, a primary SeV infection led to worsened pathologic findings on secondary heterologous viral challenge, whereas the reversed infection scheme protected against disease in response to a secondary viral challenge >1 month after the primary infection. These data demonstrate the differential effect of primary viral infections in the susceptibility to disease exacerbation in response to a different secondary viral infection and highlight the usefulness of these viral models as tools to understand the underlying mechanisms that mediate distinct chronic postviral lung diseases., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Most researchers and public health officials would agree that the causes and consequences of obesity are complex and multi-faceted. However, curricula designed to address these complexities are limited and often guided by a single discipline. The purpose of the Transdisciplinary Obesity Prevention Research Sciences (TOPRS) program was to develop a "flip-the-classroom" curriculum on obesity prevention across multiple disciplines such that students would gain an appreciation of the complex origins of obesity. The curriculum is based on the 6 C's model (cell, child, clan, community, country, culture) that proposes a cell-to-society approach to obesity. Twenty video micro-lectures were developed and students were tested on content knowledge pre- and post-viewing. The curriculum was administered at three university sites to 74 undergraduate students across 23 declared majors from 2014-2016. There were significant gains in knowledge about the causes and consequences of obesity. Recommendations are offered to adopt this curriculum in undergraduate and other educational settings.

Food insecurity is common in the United States and linked to poor control of conditions influenced by diet. We conducted a pilot randomized trial to test whether a novel partnership between a primary care practice and a municipal food bank would improve control of type 2 diabetes among patients with food insecurity. Participants received food bank produce delivered twice monthly to the practice site, brief teaching from a food bank dietitian, and home-based education from a community health worker. After 6 months, glycosylated hemoglobin decreased (absolute change) by 3.1% in the intervention group vs 1.7% in the control group ( P  = .012). Scores on Starting the Conversation-Diet, a brief dietary measure, improved in the intervention group by 2.47 on a 14-point scale ( P  < .001). Body mass indexes (BMIs) were unchanged. In this early-stage study, onsite collaboration between primary care and a regional food bank generated clinically meaningful reductions in HbA 1c and improvements in diet., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: As running speed increases there are concomitant changes in loads associated with tibial stress fracture risk. Runners often include multiple speeds in their training, but the effect of speed distribution on load accumulation is unknown. We studied how running at different proportions of speed within a given running distance affects the cumulative loading of the vertical average loading rate, cumulative peak absolute tibial free moment, and cumulative peak axial tibial load. These loads were compared between two proportions of speed: running all distance at normal self-selected speed, and running the same distance at a combination of slow/fast speeds with the same average speed as normal. Also, the contributions of slow and fast running to the combined condition were compared., Methods: Forty-three recreational runners (age, 18-49 yr; 29 female, 14 male) ran around a 50-m indoor track for three laps each at self-selected slow, normal, and fast speeds. Per-step peak loads and cumulative loads per kilometer were calculated at each speed and for each speed distribution, respectively., Results: Only cumulative vertical average loading rate was lower at normal speed compared with the slow/fast speed combination. The contribution of fast speed running to cumulative tibial load was less than the contribution of slow speed running., Conclusions: Running at a combination of slow and fast speeds, rather than a single moderate speed, increased cumulative vertical average loading rate but not cumulative tibial load or free moment. Fast running can be included in a training program without necessarily increasing the cumulative load. Total distance and average speed may not be sufficient information to estimate cumulative load from running training.

Objective: The reliability of heart rate variability (HRV) analysis is not yet fully understood, especially considering different body positions and the mathematical influence of heart rate. The aim of this study was to evaluate the reliability of HRV in supine and standing positions, with and without mathematical adjustment of HRV by the average R-R interval (iRR)., Methods: We evaluated 37 young males (23.1±4 years; 25.1±3 kg/m2). A 5-min segment of the iRR was collected in the supine and standing positions on three occasions separated by 48-hour intervals. Absolute and relative reliability of temporal and spectral indices were assessed by the coefficient of variation (CV) and the intraclass correlation coefficient (ICC), respectively., Results: We did not observe differences in HRV indices in the three occasions in the supine or standing position (p>0.05). Moderate to good reproducibility was observed for temporal and spectral indices of HRV in the supine position (ICC: 0.65-0.89; CV: 0.9-19.8). In the orthostatic position, low to good reproducibility was observed (ICC: 0.35-0.89; CV: 1.1-34.8), with higher ICCs for temporal indices. After mathematical adjustment, only a small modification in HRV reliability was observed in both positions., Conclusions: In young adult males, the mathematical adjustment of HRV by the average iRR led to a nonsignificant effect on HRV reliability. Additionally, HRV reliability is dependent on body position and the index analyzed. Promising measures in both supine and standing positions include r-MSSD and the HF band (parasympathetic indices).

The secretin receptor is a prototypic class B G protein-coupled receptor that is activated by binding of its natural peptide ligand. The signaling effects of this receptor are mediated by coupling with Gs, which activates cAMP production, and Gq, which activates intracellular calcium mobilization. We have explored the molecular basis for the coupling of each of these G proteins to this receptor using systematic site-directed mutagenesis of key residues within each of the intracellular loop regions, and studying ligand binding and secretin-stimulated cAMP and calcium responses. Mutation of a conserved histidine in the first intracellular loop (H157A and H157R) markedly reduced cell surface expression, resulting in marked reduction in cAMP and elimination of measurable calcium responses. Mutation of an arginine (R153A) in the first intracellular loop reduced calcium, but not cAMP responses. Mutation of a dibasic motif in the second intracellular loop (R231A/K232A) had no significant effects on any measured responses. Mutations in the third intracellular loop involving adjacent lysine and leucine residues (K302A/L303A) or two arginine residues separated by a leucine and an alanine (R318A/R321A) significantly reduced cAMP responses, while the latter also reduced calcium responses. Additive effects were elicited by combining the effective mutations, while combining all the effective mutations resulted in a construct that continued to bind secretin normally, but that elicited no significant cAMP or calcium responses. These data suggest that, while some receptor determinants are clearly shared, there are also distinct determinants for coupling with each of these G proteins.

Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA(-) cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA(-) cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact.

The ability of cells to migrate in response to external cues, a process known as chemotaxis, is a fundamental phenomenon in biology. It is exhibited by a wide variety of cell types in the context of embryogenesis, angiogenesis, inflammation, wound healing and many other complex physiological processes. Here, we discuss the signals that control the directed migration of the social amoebae Dictyostelium discoideum both as single cells and in the context of group migration. This multi-cellular organism has served as an excellent model system to decipher amoeboid-like leukocyte migration and has played a key role in establishing signalling paradigms in the chemotaxis field. We envision that Dictyostelium will continue to bring forward basic knowledge as we seek to understand the mechanisms regulating group cell migration.

Until now, efforts to automate cervical smear diagnosis have focused on analyzing features of individual cells. In a complex specimen such as that obtained from a cervical scrape, diagnostically significant cells may not be adequately represented or may elude detection by the automated technology. An approach is needed that extracts additional quantitative information from cervical smears beyond what the cell-by-cell approach can provide. A new methodology, contextual analysis, was developed to extract global quantitative information about cells, cell clusters, and background debris. This pilot study was designed to compare the efficacy of contextual analysis with high-resolution, single cell analysis and the analysis of intermediate cell markers. Thirty-four samples prepared as monolayers and stained with the Feulgen-Thionin/Congo Red stain were measured. Contextual analysis alone was able to classify 91% of the smears correctly; single cell analysis classified 94% of the cells correctly; and the intermediate cell analysis correctly identified the smear diagnosis for 84% of the cells. When all three analysis methods were combined into a simple smear level classifier, the overall smear classification accuracy was improved over those obtained using the three methodologies alone.

A procedure for automated analysis of cervical smears has been implemented in an image cytometry system. Smears are described exclusively in terms of global and contextual information extracted by pattern-recognition algorithms and represented by a vector of proportions of cellular object types. Linear discriminant functions, based on a Fisher criterion, are derived to classify smears with a cross-section of diagnoses into two broad categories, normal and abnormal. Results obtained from 83 smears indicate 78% correct classification. In contrast to most automated systems, good classification results were obtained in normal smears with benign changes caused by inflammation and with postmenopausal atrophia and in abnormals with mild dysplasia. These findings suggest that contextual analysis may be sensitive to subtle changes in cellular morphology and to progressive patterns of dysplasia. When used with standard isolated cell analysis, contextual analysis may provide additional complementary information for automated cervical prescreening.

A technique for the preparation of cytology slides is presented by which cells collected on a polycarbonate membrane filter are transferred to a slide by means of simultaneous pressure and fixation. Using cervical samples as a model, the influence of the filtration rate, filter pore size and duration of pressure application on cell recovery was analyzed. The present version of the preparation procedure uses manual techniques that define the operating characteristics of a fully automated procedure.

The principal objective of our group has been and continues to be the improvement of the biologic signal-to-noise ratio of the gynecologic cytologic specimen through: the dispersal of clusters and clumps, enrichment of the abnormal component of the dispersed specimen by the method of rate-zonal sedimentation under unit gravity, and monitoring the effects of these manipulations with biophysical non-destructive methods. This report is concerned only with presenting the current status of the effectiveness of our enrichment techniques both qualitatively and quantitatively. Zonal sedimentation creates a broad spatial spectrum of cells by virtue of their different velocities which are directly related to their areas. Certain fractions of this spectrum are extracted, concentrated and deposited on slides for subsequent manual differential analysis, evaluation and documentation. Qualitatively, fractions M1 and M2 show impressive removal of erythrocytes, leukocytes and debris. Quantitatively, enrichment factors vary from 0.1 (depletion) to as high as 26 yielding an average enrichment of about 6, a most rewarding improvement.

A technique of cluster disaggregation has been developed and applied to cervical cells in suspension. Preliminary results indicate that ultrasound is capable of cluster disaggregation under controlled energy conditions. Cytologic quality of the resulting preparation is adequate for cell analysis in flow systems.

We have shown that it is possible to automate the assessment of leukocyte alkaline phosphatase by using an azo dye cytochemical staining procedure and a commercial, highly sophisticated image analysis instrument originally designed specifically as a differential white cell counter. The data to date indicate that values obtained by this approach are at least as precise and accurate as current manual techniques. Instrumental analysis avoids the subjectivity associated with manual interpretation of staining intensity and should permit meaningful interlaboratory comparisons. The stability of the stained smears upon exposure to immersion oil or Polymount mounting medium proved to be an unexpected bonus. In addition to such functional data on leukocytes as illustrated by this report, these instruments, with appropriate staining methods and software, can also provide clinically useful quantitative data on red cells, as have been described for reticulocytes. We hope to see more clinical applications in the future for these expensive and target-oriented image analysis instruments. They are capable of automatically providing objective quantitative information on a cell by cell basis--providing feature data that cannot be obtained by other means.

Image analysis techniques were used to characterize individual nuclei of cells and entire clusters of cells in hematoxylin-and-eosin-stained smears of fine needle aspirates of the breast to determine the ability of these techniques to distinguish benign from malignant cases. Analysis of the individual nuclear features showed significant differences in nuclear area, shape (bending energy), texture and integrated darkness between benign and malignant samples. Analysis of the clusters demonstrated that the benign clusters were fewer in number, more cellular (average gray level) and larger than malignant clusters. A statistical classifier was constructed to test the discriminatory accuracy for benign and malignant cases. Good discrimination was found for both the individual nuclei and the clusters when analyzed separately, although a few cases were misclassified by each type of analysis. When combined, the two classifiers achieved a completely accurate classification. This suggests the complementary nature of high-resolution single-cell analysis and the more global cluster analysis techniques.

Since disaggregation for monodispersion is optimal when the specimens are suspended in solutions of low alcohol content, we evaluated a modified Davis' solution as a collection and suspension medium. The preservation of specimens maintained at room temperature (21 C) in this solution, which contained only 10% ethanol instead of the usual 20%, was evaluated both qualitatively and quantitatively. Control slides were made on day 1, and experimental slides were made on days 3, 7, 14, 21 and 28. The slides were evaluated by a cytotechnologist and confirmed by a pathologist for the onset of degenerative changes and loss of diagnostic value. The slides were also quantitatively analyzed by a semiautomatic instrument, the Cyto-Tally, adding substantial numerical value to the inquiry. The fragility of leukocytes was evident by the 14th day. Squamous cell degeneration was seen in the interval between two and four weeks depending on the initial state of the specimen. However, the specimens were of diagnostic value for up to four weeks.