Samuel J. Simmens

Depression, Perception of Illness and Mortality in Patients with End-Stage Renal Disease:

A role of depression in affecting outcome in patients with end stage renal disease (ESRD) has been suggested but few have assessed psychological parameters and medical factors thought to influence survival simultaneously and prospectively. To assess whether depression or perception of illness influences survival in patients treated for ESRD, we prospectively evaluated fifty-seven patients with ESRD treated with hemodialysis (HD, n = 43) or continuous ambulatory peritoneal dialysis (CAPD, n = 14). Patients were interviewed and completed the Beck Depression Inventory (BDI) and the Illness Effects Questionnaire (IEQ). An ESRD severity coefficient was used to measure chronic illness severity. A cognitive item subset of the BDI (CDI) was used as an additional measure of depression. One and two years later, records were examined to determine survival. When initial results of the assessment of survivors and non-survivors were compared, at one year follow-up, there were no differences in mean age, duration of dialysis, severity scores, BDI or IEQ scores. The initial mean CDI scores in the group of non-survivors, however, were significantly greater than the scores in the survivor group. At two year follow-up, CDI scores were significantly different between groups, and were significant in a hazards regression. Disease severity, age and duration of dialysis were also significantly related to mortality at two year follow-up. We conclude cognitive depression is an important, early, indicator of grave prognosis in patients treated for ESRD. Early recognition of and therapeutic efforts directed toward the treatment of depression might modify outcome in ESRD patients.

Natural disaster and depression: A prospective investigation of reactions to the 1993 Midwest Floods

A statewide sample of 1735 Iowa residents, approximately half of whom were victims of the 1993 Midwest Floods, participated in interviews 1 year prior to, and 30 to 90 days after, the disaster. Employing a rigorous methodology including both control-group comparisons and predisaster assessments, we performed a systematic evaluation of the disasters impact. Overall, the disaster led to true but small rises in depressive symptoms and diagnoses 60–90 days postflood. The disaster–psychopathology effect was not moderated by predisaster depressive symptoms or diagnostically defined depression; rather, predisaster symptoms and diagnoses uniquely contributed to increases in postdisaster distress. However, increases in symptoms as a function of flood impact were slightly greater among respondents with the lowest incomes and among residents living in small rural communities, as opposed to on farms or in cities. Implications for individual- and community-level disaster response are discussed.

Bcl‐2 Protects Neural Cells from Cyanide/Aglycemia‐Induced Lipid Oxidation, Mitochondrial Injury, and Loss of Viability

Abstract: The protooncogene bcl‐2 rescues cells from a wide variety of insults. Recent evidence suggests that the mechanism of action of Bcl‐2 involves antioxidant activity. The involvement of free radicals in ischemia/reperfusion injury to neural cells has led us to investigate the effect of Bcl‐2 in a model of delayed neural cell death. We have examined the survival of control and bcl‐2 transfectants of a hypothalamic tumor cell line, GT1‐7, exposed to potassium cyanide in the absence of glucose (chemical hypoxia/aglycemia). After 30 min of treatment, no loss of viability was evident in control or bcl‐2 transfectants; however, Bcl‐2‐expressing cells were protected from delayed cell death measured following 24–72 h of reoxygenation. Under these conditions, the rate and extent of ATP depletion in response to treatment with cyanide in the absence of glucose and the rate of recovery of ATP during reenergization were similar in control and Bcl‐2‐expressing cells. Bcl‐2‐expressing cells were protected from oxidative damage resulting from this treatment, as indicated by significantly lower levels of oxidized lipids. Mitochondrial respiration in control but not Bcl‐2‐expressing cells was compromised immediately following hypoxic treatment. These results indicate that Bcl‐2 can protect neural cells from delayed death resulting from chemical hypoxia and reenergization, and may do so by an antioxidant mechanism. The results thereby provide evidence that Bcl‐2 or a Bcl‐2 mimetic has potential therapeutic application in the treatment of neuropathologies involving oxidative stress, including focal and global cerebral ischemia.

A STD/HIV prevention trial among adolescents in managed care

Objective. To determine if sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, risk assessment, and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors. Design. A randomized intervention trial with 3- and 9-month follow-up. Setting. Five staff-model managed care sites in Washington, DC (n = 19 pediatricians). Patients. Consecutive 12- to 15-year-olds receiving a general health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month follow-up rate = 197/215 (92%). Intervention. Audiotaped STD risk assessment and education about staying safe (safer = condoms, safest = abstinence). Main Outcome Measures. Adolescent-reported sexual intercourse and condom use. Results. More intervention adolescents reported pediatrician discussion on 11/13 sexual topics. Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.04–5.84) was reported in the intervention group at 3 months, this was not true of overall sexual intercourse (OR = 1.55, 95% CI = .73–3.32). More sexually active adolescents reported condom use in the intervention group at 3 months (OR = 18.05, 95% CI = 1.27–256.03). At 9 months, there were no group differences in sexual behaviors; however, more signs of STD were reported by the control (7/103) than the intervention group (0/94). Conclusions. STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education. Any impact on sexual activity and condom use was short-lived. Further research is needed to develop brief, office-based sexual risk reduction for young adolescents.

Maternal Panic Disorder: Infant Temperament, Neurophysiology, and Parenting Behaviors

OBJECTIVE To determine whether 4- and 14-month-old infants of mothers with panic disorder (PD) would be more likely to show differences in temperament, neurophysiology (salivary cortisol and sleep), and relationships with their mothers than controls. METHOD Two cohorts were recruited: 4-month-old infants with PD mothers (n = 25) and 4-month-old controls (n = 24), and 14-month-old infants with PD mothers (n = 27) and 14-month-old controls (n = 18). Mothers completed diagnostic interviews and questionnaires concerning infant temperament, sleep, and parenting. Infant salivary cortisol samples and standard observational procedures to measure infant temperament, sleep, attachment, and parenting were also used. RESULTS Infants with PD mothers did not show more high reactivity, behavioral inhibition, or ambivalent/resistant attachment but did demonstrate different neurophysiology (higher salivary cortisol and more disturbed sleep) than controls. PD mothers also displayed less sensitivity toward their infants and reported parenting behaviors concerning infant sleep and discipline that have been associated with child problems. CONCLUSIONS While infants with PD mothers did not show early behavioral differences from controls, they did display neurophysiological divergences consistent with higher arousal/arousability. Such neurophysiological divergences (elevated salivary cortisol and disturbed sleep) might be important early indicators of risk. Helping PD mothers parent their more highly aroused/arousable infants could reduce the development of psychopathology.

Prenatal Nicotine Exposure Alters Central Cardiorespiratory Responses to Hypoxia in Rats: Implications for Sudden Infant Death Syndrome

Maternal cigarette smoking and prenatal nicotine exposure are the highest risk factors for sudden infant death syndrome (SIDS). During hypoxia, respiratory frequency and heart rate transiently increase and subsequently decrease. These biphasic cardiorespiratory responses normally serve to prolong survival during hypoxia by reducing the metabolic demands of cardiac and respiratory muscles. However, exaggerated responses to hypoxia may be life threatening and have been implicated in SIDS. Heart rate is primarily determined by the activity of brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus. We developed an in vitro rat brainstem slice preparation that maintains rhythmic inspiratory-related activity and contains fluorescently labeled CVNs. Synaptic inputs to CVNs were examined using patch-clamp electrophysiological techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic response to hypoxia from a biphasic response to a precipitous decrease in spontaneous GABAergic IPSC frequency. This study establishes a likely neurochemical mechanism for the heart rate response to hypoxia and a link between prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may contribute to SIDS.

A randomized trial of Text2Quit: a text messaging program for smoking cessation.

BACKGROUND Text messaging programs on mobile phones have shown some promise in helping people quit smoking. Text2Quit is an automated, personalized, interactive mobile health program that sends text messages to offer advice, support, and reminders about quitting smoking. PURPOSE To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. METHODS Participants (n=503) were recruited on the Internet and randomized to receive Text2Quit or self-help material. Between 2011 and 2013, participants were surveyed at baseline and at 1, 3, and 6 months post-enrollment to assess smoking status. Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up. An intent to treat analysis was used, and those lost to follow-up were categorized as smokers. All analyses were completed in 2013. RESULTS Biochemically confirmed repeated point prevalence abstinence favored the intervention group, with 11.1% abstinent compared to 5.0% of the control group (relative risk=2.22, 95% CI=1.16, 4.26, p<0.05). Similarly, self-reported repeated point prevalence abstinence was higher in the intervention group (19.9%) than in the control group (10.0%) (p<0.01). Effects were found to be uniform across the analyzed demographic subgroups, although suggestive of a larger effect for non-whites than whites. CONCLUSIONS These results provide initial support for the relative efficacy of the Text2Quit program.

Close relationships and emotional processing predict decreased mortality in women with breast cancer: preliminary evidence.

Objective: To examine close relationships and emotional processing as predictors of breast cancer mortality. Methods: Ninety women were enrolled at 14 ± 5 months after diagnosis of Stage II/III breast cancer. The Nottingham Prognostic Index (NPI) quantified disease severity. Cox proportional hazards analyses were used to predict mortality using standardized variables. Results: Twenty-one subjects developed recurrent disease and 16 died during an 8-year follow-up. NPI predicted increased mortality: risk ratio (RR) = 1.60 (CI = 1.05–2.41). Decreased mortality was predicted by confiding marriage (CONF): RR = 0.31 (CI = 0.10–0.99), and number of dependable, nonhousehold supports (SUPP): RR = 0.41 (CI = 0.21–0.80). A composite measure of close relationships (standardized CONF + SUPP = SUPPCONF) had a strong protective effect: RR = 0.30 (CI = 0.13–0.69). Two emotion processing variables, acceptance of emotion and emotional distress (POMS-TOT) were found to be negatively correlated (r = −.49). Acceptance of emotion predicted decreased mortality (RR = 0.46 (CI = 0.24–0.86)) when analyzed together with emotional distress, but not separately. There was a trend for a protective effect of emotional distress: RR = 0.37 (CI = 0.12–1.09) in the same analysis. RRs for mortality in a multivariable analysis were: SUPPCONF: RR = 0.55 (CI = 0.30–1.00); acceptance of emotion: RR = 0.48 (CI = 0.25–0.91); and emotional distress: RR = 0.40 (CI = 0.14–1.19). Conclusions: Two aspects of close relationships—marital confiding and dependable, nonhousehold supports—were protective against breast cancer progression. Acceptance of emotion, after controlling for emotional distress, also predicted decreased mortality. Analysis of close relationships together with emotion processing variables suggested unique protective effects against mortality, but a larger study is necessary to determine whether this is the case. CI = confidence interval; CONF = marital confiding; NPI = Nottingham Prognostic Index; RR = Risk Ratio; POMS-TOT = Total Mood Disturbance Score, Profile of Mood States; SUPP = number of dependable, nonhousehold supports; SUPPCONF = close relationships total.

Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse.

Adult corneal epithelial stem cells (CESCs) have been shown to reside at the periphery of the cornea at a site called the corneoscleral junction or limbus. Although studies have shown that these cells are slow cycling, their molecular characteristics are not well understood. Using a whole‐mount procedure, we show that whereas α9‐integrin is present in a subset of the basal cells at the corneal limbus and absent in the central cornea, β1‐, β4‐, α3‐, and α6‐integrins are more highly expressed overall in central corneal basal cells. To characterize CESCs based on their slow‐cycling nature, we simultaneously evaluated 5‐bromo‐2‐deoxyuridine (BrdU) label‐retaining cells (LRCs) and integrin expression (α9, β1, and β4) in a total of 1,889 cells at the limbus of adult mice that had been injected as neonates with BrdU. Whereas the LRCs were usually observed adjacent to α9‐integrin‐positive cells, most LRCs were α9‐integrin–negative and expressed high levels of β1‐ and β4‐integrin. In addition, we observed more BrdU‐positive LRCs at the superior and inferior quadrants of adult mouse corneas than at the nasal and temporal quadrants, and determined that 0.94 to 3.6% of the limbal basal cells were slow cycling. We conclude from these data that the slow‐cycling LRCs in the adult mouse cornea are enriched in cells that express high levels of β1‐ and β4‐integrin and little α9‐integrin.

The Impact of Professionally Conducted Cultural Programs on the Physical Health, Mental Health, and Social Functioning of Older Adults—2-Year Results

PURPOSE The aim of this study was to measure the impact of professionally conducted community-based cultural programs on the physical health, mental health, and social activities of individuals aged 65 and older. DESIGN AND METHODS Participants in the study were 166 healthy, ambulatory older adults from the Washington, DC, area. We assigned them to either an intervention (chorale) or comparison (usual activity) group and assessed them at baseline and after 12 months. RESULTS Results obtained from utilizing established assessment questionnaires and self-reported measures, controlling for any baseline differences, revealed positive findings for the effectiveness of the intervention such that the intervention group reported a higher overall rating of physical health, fewer doctor visits, less medication use, fewer instances of falls, and fewer other health problems than the comparison group. The intervention group also evidenced better morale and less loneliness than the comparison group. In terms of activity level, the comparison group evidenced a significant decline in total number of activities, whereas the intervention group reported a trend toward increased activity. IMPLICATIONS The positive impact of participatory art programs for older adults in this study on overall health, doctor visits, medication use, falls, loneliness, morale, and activities reflects important health promotion and prevention effects and a reduction of risk factors driving the need for long-term care.