Inner Peace in a Global Crisis: A Case Study of Supported Spiritual Individuation in Acute Onset Phase of COVID-19.

Emerging-adult undergraduates (ages 18-25) are at increased risk for mental illness, exacerbated by the COVID-19 pandemic. Simultaneously, emerging adults face developmental tasks including identity development, finding meaning and purpose, and spiritual individuation. A case study approach is used to elucidate processes of undergraduates coping with collective trauma as a potential pathway to trauma-related spiritual growth via Awakened Awareness for Adolescents (AA-A) and emerging adults, a spiritual-mind-body wellness intervention. Awakened Awareness for Adolescents fosters enhanced spiritual perception to support spiritual individuation for improved mental health and well-being. Processes of spiritual individuation supported by AA-A during the COVID-19 pandemic from February to May 2020 are presented using students' qualitative data and self-report measures of psychopathology, spiritual well-being, emotional regulation, and cognition. Shared cohort (N = 15) themes and one in-depth case (1) reveal ideographic processes of personal transformation and spiritual growth, (2) generate hypotheses around pathways of trauma-related spiritual growth and spiritual individuation for future research.

Considerations in the treatment of geriatric depression: Overview of pharmacotherapeutic and psychotherapeutic treatment interventions.

Geriatric (or late-life) depression is common in older adults, with an incidence that increases dramatically after age 70 to 85, as well as among those admitted to hospitals and those who reside in nursing homes. In this population, depression promotes disability and is associated with worsened outcomes of comorbid chronic medical diseases. Geriatric depression is often undetected or undertreated in primary care settings for various reasons, including the (incorrect) belief that depression is a normal part of aging. Current research suggests that while antidepressant agent use in older adults is improving in quality, room for improvement exists. Improving the pharmacotherapy of depression in older adults requires knowledge and understanding of many clinical factors. The purpose of this review is to discuss salient issues in geriatric depression, with a focus on pharmacotherapeutic and psychotherapeutic interventions.

Management of atypical antipsychotic drug-induced weight gain: focus on metformin.

Many patients taking atypical antipsychotic drugs will experience weight gain. Evidence suggests that long-term treatment with these agents decreases glucose effectiveness, alters satiety signals, creates hormonal resistance to satiety control, and may have a direct effect on hypothalamic appetite centers. The serotonin(2c-) and histamine(1)-receptor antagonism of atypical antipsychotics may also lead to weight gain. Several nonpharmacologic and pharmacologic methods have been used to address this adverse effect, with varying success. Metformin is an antidiabetic drug that has been shown to cause weight loss in patients with diabetes mellitus, as well as in some individuals without diabetes. To evaluate whether metformin can decrease weight gain induced by atypical antipsychotics in patients without diabetes, we conducted a literature search using the MEDLINE database (1970-October 2008) and clinicaltrials.gov Web site for relevant trials. Overall, 14 articles were identified for inclusion; review articles, case reports, and open-label studies were excluded. Thus, eight double-blind, placebo-controlled studies were reviewed; both pediatric and adult trials were included. Metformin has several advantages, including ease of use and a favorable safety profile. Although lactic acidosis was not reported in any of the studies reviewed, this potentially rare but severe adverse effect must be considered when prescribing this agent. Limited data suggest that metformin may attenuate weight gain in both adult and adolescent patients taking atypical antipsychotics. However, most of the trials included foreign populations, were only 12-16 weeks in duration, and the dosage of metformin may not have been adequately titrated. Although the study results do not provide clear substantial evidence that metformin, as an adjuvant to atypical antipsychotic use, will decrease weight gain and improve metabolic effects, they are encouraging. Additional studies of longer duration that include behavioral therapy and special diets should be conducted in patients from the United States. Currently, the drug is being used as a secondary or tertiary intervention, and its use may be considered in patients with a personal and/or family history of obesity or metabolic dysfunction, and in subjects who have rapid weight gain early in antipsychotic treatment.

Prazosin for the treatment of posttraumatic stress disorder sleep disturbances.

An estimated 70-87% of patients who suffer from posttraumatic stress disorder (PTSD) experience sleep disruption. These patients have distressing dreams or nightmares in which the traumatic event is reexperienced, and they also have difficulty in falling or staying asleep. Selective serotonin reuptake inhibitors are the treatment of choice for PTSD, but with the exception of fluvoxamine, they are often ineffective or only partially effective for sleep problems. Sedative-hypnotics may be helpful in the short term but are associated with tolerance and addiction potential. In the central nervous system, alpha(1)-adrenergic receptors are known to be important in both the startle and sleep responses. Stimulation of these receptors may contribute to PTSD-related trauma-content nightmares. Prazosin, a highly lipophilic alpha(1)-adrenergic receptor blocker that is traditionally used to treat hypertension and benign prostatic hyperplasia, has been shown to decrease the occurrence of trauma nightmares in both combat veterans and patients with non-combat-related PTSD. The available data, although mostly from open-label trials, suggest that this agent also improves sleep quality and patients' sense of wellbeing and ability to function in daily activities. The optimum dose is unknown; however, a dose-related response appears to be evident. Clinicians should monitor for orthostatic hypotension, usually seen early in therapy, when prazosin is started in patients with PTSD.

The use of cognitive enhancers in behavioral disturbances of Alzheimer's disease.

OBJECTIVE: To review the literature for double-blind, placebo-controlled trials that examined the efficacy of cognitive enhancers in the psychopathology of Alzheimer's disease. DATA SOURCES: Literature searches were conducted using MEDLINE and EMBASE databases and clinicaltrials.gov. STUDY SELECTION: Overall, 55 articles were reviewed for inclusion. Several open-label studies and case reports were found on this topic, but only those involving both tacrine and use of the Neuropsychiatric Inventory were included. Regarding other drugs, only double-blind, placebo-controlled trials were selected for inclusion. DATA SYNTHESIS: Limited data suggest that the anticholinesterase inhibitors and memantine offer an alternative or adjunct to the antipsychotics for the treatment of moderate-to-severe behaviors. The author reviewed the literature for pharmacological management of behavioral and psychological symptoms of dementia (BPSD) using these cognitive enhancers. CONCLUSION: The majority of patients with Alzheimer's disease will experience behavioral disturbances during the course of their disease. Atypical antipsychotics are used routinely in these situations to treat the psychotic features and agitation. However, atypicals now carry a "black box" warning issued by the Food and Drug Administration on the basis of evidence that their use in geriatric patients with dementia-related psychosis may put patients at increased risk of mortality as a result of cardiovascular or infectious events. An alternative to the atypicals may be the acetylcholinesterase inhibitors and memantine, which have been shown to stabilize cognitive as well as behavioral issues in patients, utilizing the "gold standard" for behavior, the Neuropsychiatric Inventory. Efficacy varies among agents, with the greatest positive effects seen with donepezil, which also has the greatest number of studies. Drug benefits were harder to demonstrate for mild-to-moderate BPSD compared with moderate-to-severe symptoms.

Quantitative analysis by flow cytometry of interstitial cells of Cajal, pacemakers, and mediators of neurotransmission in the gastrointestinal tract.

BACKGROUND: Interstitial cells of Cajal (ICCs) are mesenchymal cells that play critical roles in gastrointestinal motility as electrical pacemakers and mediators of neuromuscular neurotransmission. Although depletions of ICCs have been implicated in several gastrointestinal motor disorders, quantification of these cells has been difficult due to their varied morphology, regionally changing network density, and overall scarcity. Our goal was to evaluate flow cytometry (FCM) for the enumeration of ICCs. METHODS: We identified murine ICCs in live gastrointestinal muscles or primary cell cultures grown in the presence or absence of stem cell factor (SCF)-expressing STO fibroblasts with fluorescent Kit (CD117) antibodies. Because this technique also labels resident macrophages nonspecifically, we identified the latter with additional fluorescent antibodies. Dispersed cells were analyzed by FCM. RESULTS: ICCs represented 1.63 +/- 0.17% of the total cell count in the distal stomach (n = 18 mice) and 5.85 +/- 0.84% in the proximal colon and 6.28 +/- 0.61% in the distal colon (n = 3 mice). In fundic muscles of W/WV mice (n = 5) that virtually lack ICCs, very few Kit+ cells were detected. FCM identified approximately 2.6- to 7.3-fold more Kit+ ICCs in small intestinal cell cultures grown on STO fibroblasts expressing membrane-bound SCF (n = 6) than in cultures stimulated with soluble SCF (n = 6). CONCLUSIONS: FCM is a sensitive and specific method for the unbiased quantification of ICCs.

The role of cholesterol and statins in Alzheimer's disease.

OBJECTIVE: To briefly discuss the impact of elevated total and low-density-lipoprotein cholesterol levels, as well as the potential relationship of hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use, on the development of Alzheimer's disease (AD). DATA SOURCES: Biomedical literature was accessed through MEDLINE and International Pharmaceutical Abstracts (1966-June 2003). The authors independently reviewed literature for possible inclusion in this article. STUDY SELECTION AND DATA EXTRACTION: Clinical studies were selected and reviewed from the data sources, with special emphasis on those dealing with statin use and AD. DATA SYNTHESIS: The impact of AD is significant, as it is rapidly becoming one of our country's most debilitating and costly diseases. Data from epidemiologic trials indicate that statins may have some protective effect against the development of AD. These trials also allude to theories regarding possible mechanisms of action for this use, data implicating possible superiority of one statin over another, and their lack in certain populations, specifically the very old elderly population. CONCLUSIONS: Preliminary evidence suggests that statins may offer a protective effect against the development of AD. However, review of the literature does not lend credence to the use of statins in the general nondemented population without hyperlipidemia. Potential confounding variables have not been considered in the majority of trials. Placebo-controlled clinical trials are ongoing and should yield more definitive results.

Purification of interstitial cells of Cajal by fluorescence-activated cell sorting.

Interstitial cells of Cajal (ICC) in the gastrointestinal tract generate and propagate slow waves and mediate neuromuscular neurotransmission. Although damages to ICC have been described in several gastrointestinal motor disorders, analysis of their gene expression in health and disease has been problematic because of the difficulties in isolating these cells. Our goal was to develop techniques for large-scale purification of ICC. Murine ICC were identified in live gastrointestinal muscles with fluorescent Kit antibodies. Because this technique also labels resident macrophages nonspecifically, we attempted to separate ICC from these cells by fluorescence-activated cell sorting with or without immunomagnetic presorting. Efficacy and specificity of ICC purification were tested by quantitative RT-PCR of cell-specific markers. Fluorescence-based separation of small intestinal ICC from unlabeled cells and macrophages tagged with F4/80 antibodies yielded 30,000-40,000 cells and approximately 60-fold enrichment of c-kit mRNA. However, the macrophage marker CD68 was also enriched approximately 6-fold. Magnetic presorting of ICC did not significantly improve selectivity. After labeling contaminating cells with additional paramagnetic (anti-CD11b, -CD11c) and fluorescent antibodies (anti-CD11b) and depleting them by magnetic presorting, we harvested approximately 2,000-4,000 cells from single gastric corpus-antrum muscles and detected an approximately 30-fold increase in c-kit mRNA, no enrichment of mast cells, and an approximately 4-fold reduction of CD68 expression. Adding labeled anti-CD45 antibody to our cocktail further increased c-kit enrichment and eliminated mast cells and macrophages. Smooth muscle cells and myenteric neurons were also depleted. We conclude that immunofluorescence-based sorting can yield ICC in sufficiently high numbers and purity to permit detailed molecular analyses.

The large conductance potassium channel beta-subunit can interact with and modulate the functional properties of a calcium-activated chloride channel, CLCA1.

We have recently compared the biophysical and pharmacological properties of native Ca(2+)-activated Cl(-) currents in murine portal vein with mCLCA1 channels cloned from murine portal vein myocytes (Britton, F. C., Ohya, S., Horowitz, B., and Greenwood, I. A. (2002) J. Physiol. (Lond.) 539, 107-117). These channels shared a similar relative permeability to various anions, but the expressed channel current lacked the marked time dependence of the native current. In addition, the expressed channel showed a lower Ca(2+) sensitivity than the native channel. As non-pore-forming regulatory beta-subunits alter the kinetics and increase the Ca(2+) sensitivity of Ca(2+)-dependent K(+) channels (BK channels) we investigated whether co-expression of beta-subunits with CLCA1 would alter the kinetics/Ca(2+) sensitivity of mCLCA1. Internal dialysis of human embryonic kidney cells stably expressing CLCA1 with 500 nM Ca(2+) evoked a significantly larger current when the beta-subunit KCNMB1 was co-expressed. In a small number of co-transfected cells marked time dependence to the activation kinetics was observed. Interaction studies using the mammalian two-hybrid technique demonstrated a physical association between CLCA1 and KCNMB1 when co-expressed in human embryonic kidney cells. These data suggest that activation of CLCA1 can be modified by accessory subunits.

Serotonergic agents in the treatment of fibromyalgia syndrome.

OBJECTIVE: To evaluate literature that discusses the treatment of fibromyalgia syndrome (FMS) with agents that involve the neurotransmitter serotonin. DATA SOURCES: Biomedical literature accessed through MEDLINE (1966-August 2001) and International Pharmaceutical Abstracts. DATA SYNTHESIS: The cause and pathophysiology of FMS remain elusive, although abnormalities in the serotonin pathway have been implicated. Several serotonergic agents have been studied for use in FMS. Trials and case reports focusing on the use of newer agents: the selective serotonin reuptake inhibitors, venlafaxine and tramadol, were reviewed. CONCLUSIONS: Current research suggests that the serotonergic agents may reduce at least some of the symptoms of FMS. However, medications that act on multiple neurotransmitters may prove to be more effective in symptom management. Additional long-term studies are required in order to validate these results.