Correlates of self-rated health in people with diabetic peripheral neuropathy: a longitudinal study.

AIM: Self-rated health, a measure of self-reported general health, is a robust predictor of morbidity and mortality in various populations, including persons with diabetes. This study examines correlates of self-rated health in adults with diabetic peripheral neuropathy (DPN). METHODS: Participants recruited from the UK and USA (n = 295; mean (± sd) age: 61.5 ± 10.7 years; 69% male; 71% type 2 diabetes) rated their health at baseline and 18 months. DPN severity was assessed using the neuropathy disability score and the vibration perception threshold. Validated self-report measures assessed neuroticism, DPN-symptoms of pain, unsteadiness and reduced sensation in feet, DPN-related limitations in daily activities, DPN-specific emotional distress and symptoms of depression. RESULTS: In the fully adjusted baseline model, younger age, presence of cardiovascular disease and higher depression symptom scores showed likely clinically meaningful independent associations with worse health ratings. Being at the UK study site and presence of nephropathy indicated potentially meaningful independent associations with lower baseline health ratings. These predictors were largely consistent in their association with health ratings at 18 months. CONCLUSION: Results identify independent correlates of health ratings among adults with DPN. Future research should investigate the clinical implications of associations and examine changes in these variables over time and potential effects on changes in health perceptions. If these associations reflect causal pathways, our results may guide interventions to target issues that are likely to have an impact on subjectively experienced health as an important patient-reported outcome in DPN care.

Diabetes-specific self-esteem, self-care and glycaemic control among adolescents with Type 1 diabetes.

AIMS: To explore the relationships between diabetes-specific self-esteem, self-care and glycaemic control among diverse adolescents with Type 1 diabetes. METHODS: Adolescents (aged 13-21 years) diagnosed with Type 1 diabetes for at least one year, receiving care at an urban medical centre, completed a self-report battery including demographic information, the Diabetes-Specific Self-Esteem Scale and Self-Care Inventory. Glycaemic control (HbA1c ) was obtained from medical records at recruitment and one year later. Bivariate correlation and multiple linear regression assessed relationships between the Diabetes-Specific Self-Esteem scale, Self-Care Inventory and HbA1c at baseline and one year. RESULTS: Participants included 85 adolescents (15.9 ± 2.1 years; 53% women; 47% Hispanic/Latino). Diabetes-specific self-esteem scores did not differ based on patient characteristics but were significantly correlated with baseline self-care (r = 0.59, P < 0.001) and HbA1c at baseline (r = -0.51, P < 0.001) and one year later (r = -0.48, P < 0.001). Diabetes-specific self-esteem remained a significant correlate of baseline (ß = -0.41, P < 0.001) and follow-up HbA1c (ß = -0.37, P = 0.008) when adjusting for covariates and self-care. Diabetes-specific self-esteem was not significantly associated with change in HbA1c . CONCLUSIONS: Results suggest that diabetes-specific self-esteem is significantly associated with self-care and glycaemic control among diverse adolescents with Type 1 diabetes. Diabetes-specific self-esteem may be more closely related to HbA1c than reports of the frequency of self-care behaviours, and could represent a useful tool for clinical and research applications.

Physical symptom complaints, cognitive emotion regulation strategies, self-compassion and diabetes distress among adults with Type 2 diabetes.

AIMS: Diabetes-related distress is common among adults with Type 2 diabetes and is consistently associated with poorer self-management and treatment outcomes. However, little is known about the psychological factors that may contribute to or protect against diabetes distress. This study examined illness burden, and positive and negative ways of thinking and relating to oneself in times of stress, as independent correlates of diabetes distress, cross sectionally and longitudinally. METHOD: A total of 120 adults treated for Type 2 diabetes reported their physical symptom complaints, cognitive emotion regulation, self-compassion and diabetes distress at baseline; 110 completed a 3-month follow-up assessment of diabetes distress. Pearson correlations and multivariable linear regression tested baseline and longitudinal relationships. RESULTS: Baseline diabetes distress was associated with greater use of negative cognitive emotion regulation strategies (r = 0.43, P < 0.01), greater tendency towards self-criticism, self-judgement and over-identification (r = 0.37, P < 0.01), and greater physical symptom burden (r = 0.50, P < 0.01). Baseline physical symptoms and negative cognitive emotion regulation were independently associated with baseline diabetes distress. Baseline physical symptoms and negative aspects of self-compassion significantly predicted diabetes distress over 3 months. Positive aspects of cognitive emotion regulation and self-compassion were not independently associated with diabetes distress cross sectionally or longitudinally. CONCLUSION: Greater symptom burden along with the use of negative cognitive emotion regulation and negative aspects of self-compassion were independently associated with diabetes distress. If these relations are explained by causal influence, these modifiable factors could be fruitful targets for intervention research.

Successful self-management among non-insulin-treated adults with Type 2 diabetes: a self-regulation perspective.

AIMS: To clarify the role of self-monitoring of blood glucose (SMBG) in the self-management of Type 2 diabetes from the patient's perspective, using in-depth interviews with non-insulin-treated adults to investigate how they learned to manage their diabetes effectively and whether SMBG played a significant role in this process. METHODS: Individual interviews were conducted with 14 non-insulin-treated adults with Type 2 diabetes who had significantly improved their glycaemic control [64% women; 50% black; 21% Hispanic; mean age 60 years; mean HbA(1c) concentration 43 mmol/mol (6.1%)]. Interviews were transcribed and analysed by a coding team, applying the concept of illness coherence from the Common Sense Model of Self-Regulation. RESULTS: The majority of participants relied on SMBG to evaluate their self-management efforts. Key themes included: adopting an experimental approach; experiencing 'a-ha' moments; provider-assisted problem-solving; using SMBG and other feedback to evaluate when their efforts were working; and normalizing diabetes-specific behaviour changes as being healthy for everyone. CONCLUSIONS: Our qualitative data are consistent with the argument that SMBG, if implemented appropriately with enough education and provider access, can be a powerful tool for non-insulin-treated adults with Type 2 diabetes to monitor their self-management. Establishing sufficient conditions for illness coherence to develop while individuals are learning to use SMBG could increase their sense of personal control in managing a complex and demanding illness.

A Social Ecological Model of Syndemic Risk affecting Women with and At-Risk for HIV in Impoverished Urban Communities.

Syndemic risk is an ecological construct, defined by co-occurring interdependent socio-environmental, interpersonal and intrapersonal determinants. We posited syndemic risk to be a function of violence, substance use, perceived financial hardship, emotional distress and self-worth among women with and at-risk for HIV in an impoverished urban community. In order to better understand these interrelationships, we developed and validated a system dynamics (SD) model based upon peer-reviewed literature; secondary data analyses of a cohort dataset including women living with and at-risk of HIV in Bronx, NY (N = 620); and input from a Bronx-based community advisory board. Simulated model output revealed divergent levels and patterns of syndemic risk over time across different sample profiles. Outputs generated new insights about how to effectively explore multicomponent multi-level programs in order to strategically develop more effective services for this population. Specifically, the model indicated that effective multi-level interventions might bolster women's resilience by increasing self-worth, which may result in decreased perceived financial hardship and risk of violence. Overall, our stakeholder-informed model depicts how self-worth may be a major driver of vulnerability and a meaningful addition to syndemic theory affecting this population.

The confusing tale of depression and distress in patients with diabetes: a call for greater clarity and precision.

Studies have identified significant linkages between depression and diabetes, with depression associated with poor self-management behaviour, poor clinical outcomes and high rates of mortality. However, findings are not consistent across studies, yielding confusing and contradictory results about these relationships. We suggest that there has been a failure to define and measure 'depression' in a consistent manner. Because the diagnosis of depression is symptom-based only, without reference to source or content, the context of diabetes is not considered when addressing the emotional distress experienced by individuals struggling with diabetes. To reduce this confusion, we suggest that an underlying construct of 'emotional distress' be considered as a core construct to link diabetes-related distress, subclinical depression, elevated depression symptoms and major depressive disorder (MDD). We view emotional distress as a single, continuous dimension that has two primary characteristics: content and severity; that the primary content of emotional distress among these individuals include diabetes and its management, other life stresses and other contributors; and that both the content and severity of distress be addressed directly in clinical care. We suggest further that all patients, even those whose emotional distress rises to the level of MDD or anxiety disorders, can benefit from consideration of the content of distress to direct care effectively, and we suggest strategies for integrating the emotional side of diabetes into regular diabetes care. This approach can reduce confusion between depression and distress so that appropriate and targeted patient-centred interventions can occur.

Depression predicts first but not recurrent diabetic foot ulcers.

AIMS/HYPOTHESIS: This study examined the relationship between symptoms of depression and the development of diabetic foot ulcers. METHODS: Participants were 333 patients (71% male; mean age 62 years; 73% with type 2 diabetes) with diabetic peripheral neuropathy (DPN), but without peripheral vascular disease (PVD). Severity of DPN and the presence of PVD were assessed by clinical examination. Depression, other diabetes complications and foot self-care were assessed by self-report. Cox regression tested whether depression was an independent predictor of foot ulceration over 18 months, whether this relationship was moderated by foot ulcer history, and whether foot self-care mediated this relationship. RESULTS: During follow-up, 63 patients developed a foot ulcer. Those with prior foot ulcers had more than four-fold greater risk of subsequent foot ulceration compared with those without a history of foot ulcer. A significant interaction effect showed that depression was significantly related to the development of first but not recurrent foot ulcers. This relationship was independent of biological risk factors. In the final model, each standard deviation increase in depression symptoms was significantly associated with increased risk of developing first foot ulcers (HR 1.68, 95% CI 1.20-2.35), while foot self-care was associated with lower risk (HR 0.61, 95% CI 0.40-0.94). Foot self-care did not mediate the relationship between depression and foot ulceration. CONCLUSIONS/INTERPRETATION: These data suggest that depression is associated with increased risk of first foot ulcers in DPN patients and that this relationship is independent of biological risk factors and foot self-care. Interventions that target depression and foot self-care before the development of foot ulcers may maximise the likelihood of successful prevention of foot ulceration.

Decrease of ruminal methane production in Rusitec fermenters through the addition of plant material from rhubarb (Rheum spp.) and alder buckthorn (Frangula alnus).

Roots of rhubarb (Rheum spp.) and bark of alder buckthorn (Frangula alnus) were tested as feed additives for decreasing ruminal methane production released from anaerobic fermentation of a forage-based diet in a rumen-simulating fermenter (Rusitec). Sixteen fermentation units (vessels) were set up for the experiment lasting 19 d. Treated vessels were supplied with 1g/d of rhubarb or alder buckthorn (4 vessels per plant species); another 4 vessels received 12 microM sodium monensin (positive control), and the remaining 4 vessels were controls (no additive). Upon termination of the experimental period, batch cultures were inoculated with the liquid contents of the vessels for examining in vitro fermentation kinetics of cellulose, starch, barley straw, and the same substrate used in the Rusitec cultures. Monensin induced changes in fermentation in agreement with those reported in the literature, and inocula from those cultures decreased the fermentation rate and total gas produced in the gas kinetics study. Rhubarb decreased methane production, associated with limited changes in the profile of volatile fatty acids throughout the duration of the study, whereas digestibility and total volatile fatty acids production were not affected. Rhubarb inocula did not affect gas production kinetics except for cellulose. Alder buckthorn decreased only methane concentration in fermentation gas, and this effect was not always significant. The use of rhubarb (milled rhizomes of Rheum spp.) in the diets of ruminants may effectively modulate ruminal fermentation by abating methane production, thus potentially involving productive and environmental benefits.

Predictors of depressive symptoms in persons with diabetic peripheral neuropathy: a longitudinal study.

AIMS/HYPOTHESIS: The aim of the study was to determine whether diabetic peripheral neuropathy (DPN) is a risk factor for depressive symptoms and examine the potential mechanisms for this relationship. METHODS: This longitudinal study (9 and 18 month follow-up) of 338 DPN patients (mean age 61 years; 71% male; 73% type 2 diabetes) examined the temporal relationships between DPN severity (mean +/- SD; neuropathy disability score [NDS], 7.4 +/- 2.2; mean vibration perception threshold, 41.5 +/- 9.5 V), DPN somatic experiences (symptoms and foot ulceration), DPN psychosocial consequences (restrictions in activities of daily living [ADL] and social self-perception) and the Hospital Anxiety and Depression subscale measuring depressive symptoms (HADS-D; mean 4.9 +/- 3.7). RESULTS: Controlling for baseline HADS-D and demographic/disease variables, NDS at baseline significantly predicted increased HADS-D over 18 months. This association was mediated by baseline unsteadiness, which was significantly associated with increased HADS-D. Baseline ADL restrictions significantly predicted increased HADS-D and partly mediated the association between baseline unsteadiness and change in HADS-D. Increased pain, unsteadiness and ADL restrictions from baseline to 9 months each significantly predicted increased HADS-D over 18 months. Change in social self-perception from baseline to 9 months significantly predicted increased HADS-D and partly mediated the relationships of change in unsteadiness and ADL restrictions with change in HADS-D. CONCLUSIONS/INTERPRETATION: These results confirm that neuropathy is a risk factor for depressive symptoms because it generates pain and unsteadiness. Unsteadiness is the symptom with the strongest association with depression, and is linked to depressive symptoms by perceptions of diminished self-worth as a result of inability to perform social roles.

Symptoms of depression prospectively predict poorer self-care in patients with Type 2 diabetes.

AIMS: To examine prospectively the association of depression symptoms with subsequent self-care and medication adherence in patients with Type 2 diabetes mellitus. METHODS: Two hundred and eight primary care patients with Type 2 diabetes completed the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) and the Summary of Diabetes Self-Care Activities (SDSCA) at baseline and at follow-up, an average of 9 months later. They also self-reported medication adherence at baseline and at a follow-up. RESULTS: Baseline HANDS scores ranged from 0 to 27, with a mean score of 5.15 +/- 4.99. In separate linear regression models that adjusted for baseline self-care, patients with higher levels of depressive symptoms at baseline reported significantly lower adherence to general diet recommendations and specific recommendations for consumption of fruits and vegetables and spacing of carbohydrates; less exercise; and poorer foot care at follow-up (beta ranging from -0.12 to -0.23; P < 0.05). Similarly, each one-point increase in baseline HANDS score was associated with a 1.08-fold increase in the odds of non-adherence to prescribed medication at follow-up (95% confidence interval 1.001, 1.158, P = 0.047). Increases in depression scores over time also predicted poorer adherence to aspects of diet and exercise. CONCLUSIONS: Depressive symptoms predict subsequent non-adherence to important aspects of self-care in patients with Type 2 diabetes, even after controlling for baseline self-care. Although the relationship between symptoms of depression and poorer diabetes self-care is consistent, it is not large, and interventions may need to address depression and self-care skills simultaneously in order to maximize effects on diabetes outcomes.

Adapting and validating a measure of diabetes-specific self-compassion.

AIMS: Self-compassion (SC), or treating oneself with kindness when dealing with personal challenges, has not been rigorously examined in people with T1D. SC has been shown to buffer against negative emotions and to be linked to improved health outcomes, but diabetes-specific SC has not been studied. This study aimed to adapt the Self-Compassion Scale and validate it for a diabetes-specific population. METHODS: We developed and validated a diabetes-specific version of the Self-Compassion Scale (Neff, 2003) in a sample of adults with T1D (N=542; 65% female; 97% non-Hispanic White; M age 41, SD=15.7; M A1c=7.3, SD=1; 72% insulin pump users; 50% continuous glucose monitoring [CGM] users). Confirmatory factor analyses (CFA), and reliability and construct validity analyses were conducted. Validity measures included diabetes distress, diabetes empowerment, diabetes numeracy, and A1c. RESULTS: A two-factor bi-factor structure showed best fit, providing support for use of the adapted scale (SCS-D) as a unitary construct. The 19-item unidimensional SCS-D demonstrated excellent internal consistency (ɑ=0.94; range of item-total correlations: 0.52-0.71) and construct validity. As hypothesized, higher SCS-D was associated with less distress, greater empowerment, and lower A1c, and was not associated with numeracy. CONCLUSIONS: The SCS-D is a reliable and valid measure of diabetes-specific self-compassion in adults with T1D.

Diabetes distress from the patient's perspective: Qualitative themes and treatment regimen differences among adults with type 2 diabetes.

AIMS: To explore diabetes distress in a sample of adults with type 2 diabetes, treated and not treated with insulin. METHODS: Six focus groups were conducted with 32 adults with type 2 diabetes, divided by treatment regimen (insulin-treated N=15; 67% female; 60% black; 46% Hispanic; M age 54; M HbA1c 73mmol/mol (8.8%); non-insulin-treated N=17; 53% female; 65% black; 13% Hispanic; M age 58; M HbA1c 55mmol/mol (7.2%)). A coding team transcribed and analyzed interviews to describe themes. Themes were then compared between groups and with existing diabetes distress measures. RESULTS: Participants in both groups described a range of sources of diabetes distress, including lack of support/understanding from others, difficulties communicating with providers, and distress from the burden of lifestyle changes. Insulin-treated participants described significant emotional distress related to the burden of their insulin regimen. They were more likely to report physical burden related to diabetes; to describe feeling depressed as a result of diabetes; and to express distress related to challenges with glycemic control. Non-insulin-treated participants were more likely to discuss the burden of comorbid medical illnesses. CONCLUSIONS: Our data generate hypotheses for further study into the emotional burdens of diabetes for insulin-treated adults with type 2 diabetes and are in line with quantitative research documenting increased diabetes-related distress among insulin-treated individuals. Data describe needs, currently unmet by most models of care, for comprehensive assessment and tailored management of diabetes-related distress.

Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-ß2 microglobulin complexes.

Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a potent epitope recognized by CD8+ T cells in murine models. Likewise, the T2 cell line has been used as an antigen-presenting cell to activate CD8+ T cells, but so far MUC1 has not been assessed in this context. We evaluated whether the MUC1-8-mer peptide can be presented by T2 cells to expand CD25+CD8+ T cells isolated from HLA-A2+ lung adenocarcinoma patients with stage III or IV tumors. The results showed that MUC1-8-mer peptide-loaded T2 cells activated CD8+ T cells from cancer HLA-A2+ patients when anti-CD2, anti-CD28 antibodies and IL-2 were added. The percentage of CD25+CD8+ T cells was 3-fold higher than those in the non-stimulated cells (P=0.018). HLA-A2+ patient cells showed a significant difference (2.3-fold higher) in activation status than HLA-A2+ healthy control cells (P=0.04). Moreover, 77.6% of MUC1-8-mer peptide-specific CD8+ T cells proliferated following a second stimulation with MUC1-8-mer peptide-loaded T2 cells after 10 days of cell culture. There were significant differences in the percentage of basal CD25+CD8+ T cells in relation to the cancer stage; this difference disappeared after MUC1-8-mer peptide stimulation. In conclusion, expansion of CD25+CD8+ T cells by MUC1-8 peptide-loaded T2 cells plus costimulatory signals via CD2, CD28 and IL-2 can be useful in adoptive immunotherapy.

Prevalencia del Molar en C: estudio Transversal / Prevalence of C-Shaped Molar: cross-sectional Study

El objetivo fue evaluar mediante tomografía computarizada de haz cónico (CBCT), la prevalencia y tipología de conductos en C en molares inferiores. Se analizaron 422 CBCT y 1105 molares inferiores de pacientes de ambos géneros, mayores de 10 años, obtenidas en 2018. Variables registradas: género, número de pieza, y tipología, según clasificación anatómica de Fan, en los tres tercios. Se observaron cortes coronario, medio y apical. Se compararon frecuencias observadas con frecuencias esperadas bajo suposición de independencia, se utilizó prueba de bondad de ajuste de Chi-cuadrado. La comparación de pares de porcentajes se realizó con prueba de diferencia de proporciones de Pearson Chi-cuadrado con p-valores simulados por prueba de Monte Carlo. Según los resultados, el molar en C no se distribuyó homogéneamente en las tomografías analizadas. Chi-cuadrado (X2=264.13 p-valor <2,2) (p-valor dos colas <0.001), tampoco se distribuyó homogéneamente en el total de piezas dentarias Chi-cuadrado (X2=1011,1, p-valor <2.2e-16) (p-valor dos colas <0.001). Las variables género y presencia de molar en C no se distribuyeron independientemente, Chi-cuadrado (X2=4.7367, p-valor =0,042) (p-valor<0,05). Las variables tipología y piezas dentarias no se distribuyeron independientemente, Pearson Chi-cuadrado (p-valor<0.001), al igual que las variables tipología y tercios, Pearson Chi-cuadrado (p-valor<0.001). En conclusión, la CBCT es valiosa para identificar estas anatomías. Haber encontrado mayor prevalencia de tipología I confirma lo establecido en la literatura. Tienen alta prevalencia en las poblaciones asiáticas pero en caucásica son poco frecuentes (3%) (AU)

Evasion mechanisms to tumor necrosis factor alpha (TNF-alpha) of small cell lung carcinoma and non-small cell lung carcinoma cell lines: comparison with the erythroleukaemia K-562 cell line.

The tumour necrosis factor alpha (TNF-alpha) is produced by mononuclear phagocytes as a defence mechanism against malignant cells. However, these cells can evade destruction by TNF-alpha. The present study evaluates in three lung cancer cell lines (small cell carcinoma NCI-H69, adenocarcinoma A-427, squamous carcinoma SK-MES-1) and one erythroleukaemia (K-562) cell line the following evasion mechanisms: (1) inhibition of TNF-alpha production, in indirect and direct co-cultures with monocytes; (2) the expression of type I and type II receptors for TNF-alpha (TNFRI and TNFRII) by tumour cell lines, using indirect immunofluorescence and flow cytometry; (3) the sensitivity of tumour cell lines to the toxic action of recombinant human TNF-alpha (rhTNF-alpha). With the exception of cell line NCI-H69, the other tumour cell lines liberated soluble factors that inhibited TNF-alpha production in monocytes. This effect occurred even after membrane contact with the A-427 and SK-MES-1 cell lines. Erythroleukaemia K-562 cells expressed both types of receptors for TNF-alpha, whereas the NCI-H69 cells expressed only TNFRI, and the A-427 and SK-MES-1 cells expressed no receptors. Lines NCI-H69, A-427 and K-562 were insensitive to the cytotoxic action of rhTNF-alpha. In conclusion, different lung cancer cell lines may evade destruction by TNF-alpha by various mechanisms that range from blocking TNF-alpha production by monocytes to blocking the cytotoxic action of this molecule. For selecting the most effective immunotherapy, knowledge of the evasion mechanisms would be useful.

Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin.

Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.

Regions in the brainstem and frontal cortex where electrical stimulation elicits parotid and submandibular saliva secretion in sheep.

Acute experiments were conducted in sheep anaesthetized with sodium pentobarbital to identify regions in the brain where electrical stimulation would elicit secretion by the parotid and submandibular salivary glands. This was a prerequisite for single unit studies in the future. In the brainstem, parotid and submandibular secretions were evoked on average between 7 and 16 mm rostral to obex and from 1 to 11 mm lateral to midline, with the parotid gland being active on the caudal and the submandibular on the rostral sides of this region. Overlap of the two sites was common. The combined region was either between cranial nerves VII and IX or adjacent to either one of them. Stimulating the caudal edge of the parotid sites evoked relatively high parotid secretion rates compared with other areas whereas secretions were uniform throughout the submandibular sites. The combined sites were from 2 to 5 mm deep, the dorsal edge being 1 mm below the floor of the fourth ventricle near midline and 6 mm below it at the lateral extremes. From a dorsal perspective, their orientation was essentially in the lateral plane except that the submandibular site angled slightly rostrally from midline. Profuse parotid secretion was also consistently evoked by stimulating the frontal cortex 15-20 mm from midline and 0-15 mm under the apex. Weak submandibular responses were observed in about half of the sheep. There were no effects on either gland of stimulating the olfactory bulbs. This is the first report of the regions in the brain which increase parotid and submandibular saliva secretion in ruminants. The three-dimensional representation of both sites in the brainstem of individual animals is more precise than the composite representations published to date for other species.

Electrical stimulation of the medial frontal lobe elicits a pattern of body movements in sheep.

Acute experiments were conducted in sheep anaesthetized with sodium pentobarbital to identify regions in the brain where electrical stimulation would elicit movements of body parts. Stimulating the dorsal frontal cortex 2 mm from midline from the front of the brain backward for 30 mm caused movements, in order, of the lower jaw, face in general, neck, shoulder and front and back legs.

DNA-printing: utilization of a standard inkjet printer for the transfer of nucleic acids to solid supports.

The use of total cDNA as a probe for hybridization enables the transcription level of a large number of genes to be analyzed at the same time. Some effort has been spent to develop high density gene arrays on different solid supports to facilitate this hybridization. We achieved a high resolution by utilizing inkjet printer technology as a useful alternative to blotting the target genes onto a membrane. By the use of an ordinary inkjet printer model we show that it is possible to print DNA onto hybridization membranes and hybridize using either specific genes or total cDNA as probes. The high resolution of these prints (300 dpi) might be used in the future to construct complex micro-arrays to analyze simultaneously large numbers of genes.