Statin Therapy and Pancreatitis: A Multi-Institutional Retrospective Analysis.

INTRODUCTION:  Acute pancreatitis is a serious condition that has numerous etiologies and often requires hospital admission due to its high mortality rates. Statins are used worldwide to reduce the risk of cardiovascular disease. Some studies have shown an association between long-term statin use and acute pancreatitis. However, other studies have shown no effect or even postulated a mild protective effect. Due to conflicting information in the medical literature, the relationship between statins and acute pancreatitis remains unclear. The current study uses the TriNetX global research database to further investigate the impact of statin use on the development of acute pancreatitis over a five-year period. METHODS:  Two cohorts were created using the TriNetX global research database. One group consisted of patients not taking statins, while the other group included patients taking any statins. Patients in both groups were required to be between the ages of 40 and 75 and had normal low-density lipoprotein cholesterol (LDL) (≤200 mg/dl) and triglyceride (≤150 mg/dl) levels. Patients were matched for age, gender, race, and comorbidities. The statin group was then compared to the no-statin group and measured for the outcome of the incidence of acute pancreatitis and the frequency of episodes within the first five years of statin use. Patients who experienced any acute pancreatitis episode before starting statin therapy or before meeting inclusion criteria were excluded from the study. RESULTS:  Patients on statin therapy were significantly more likely to develop acute pancreatitis compared to patients not taking statin therapy (risk ratio 1.332, 95% CI: 1.242-1.429, P<0.0001). However, the statin group had a lower mean number of pancreatitis episodes than the no-statin group (4.6 vs. 5.3, P=0.043). CONCLUSION:  The results from this large global dataset support the previously established idea that prolonged use of statins is associated with an increased risk of pancreatitis. Clinicians should strongly consider statin-induced pancreatitis when other common etiologies have been ruled out.

Development of a pilot interprofessional education workshop for healthcare students and assessment of interprofessional collaborative competency attainment.

We describe the development and student evaluation of a collaborative health service provider and higher education institution initiative designed to deliver an Interprofessional Education (IPE) pilot workshop program for healthcare students. The aim was to investigate whether an IPE workshop would result in improved student confidence in self-reported interprofessional competencies using the Interprofessional Collaborative Competency Attainment Scale (ICCAS) tool. The workshops involved interprofessional student groups working on a patient case followed by a facilitator-led discussion and patient representative interaction. There were three different voluntary, extra-curricular workshops. A total of 99 students registered, from 3rd to 5th year undergraduate and 2nd year graduate entry healthcare programs at a single Irish university in February 2022. Ninety-three post-workshop survey responses showed statistically significant improvements in the ICCAS subscales of Communication, Collaboration, Roles and Responsibilities, Collaborative Patient/Family-Centered Approach, and Team Functioning; Conflict Management showed less change. Students reported positively on the benefit of the patient representative, the workshop format, and the opportunity to collaborate with students from other professions. Our findings indicate that this was a beneficial and effective way to deliver IPE across a range of healthcare professions that led to improvements in self-reported interprofessional competencies.

Clinical practice guidelines for the antenatal management of dichorionic diamniotic twin pregnancies: a systematic review.

OBJECTIVE: This review aimed to identify guidelines with recommendations applicable to the antenatal management of dichorionic diamniotic twin pregnancies within high-income countries, appraise their methodological quality, and discuss the similarities and variability across guidelines. METHOD: A systematic literature review of electronic databases was performed. Manual searches of guideline repositories and websites of professional organisations were performed to identify additional guidelines. The protocol for this systematic review was registered on PROSPERO (CRD42021248586, 25 June 2021). AGREE II and AGREE-REX tools were applied to assess the quality of eligible guidelines. A narrative and thematic synthesis described and compared the guidelines and their recommendations. RESULTS: Twenty-four guidelines were included, from which 483 recommendations were identified across 4 international organisations and 12 countries. Guidelines addressed eight themes and recommendations were classified accordingly: chorionicity and dating (103 recommendations), fetal growth (105 recommendations), termination of pregnancy (12 recommendations), fetal death (13 recommendations), fetal anomalies (65 recommendations), antenatal care (65 recommendations), preterm labour (56 recommendations) and birth (54 recommendations). Guidelines showed significant variability in recommendations, with conflicting recommendations regarding non-invasive preterm testing, definitions surrounding selective fetal growth restriction, screening for preterm labour and the timing of birth. Guidelines lacked a focus on standard antenatal management of DCDA twins, management of discordant fetal anomaly and single fetal demise. CONCLUSIONS: Specific guidance for dichorionic diamniotic twins is overall indistinct and access to guidance regarding the antenatal management of these pregnancies is currently difficult. Management of discordant fetal anomaly or single fetal demise needs greater consideration.

Facilitators and barriers influencing weight management behaviours during pregnancy: a meta-synthesis of qualitative research.

BACKGROUND: Obesity and overweight are considered risk factors for a range of adverse outcomes, including stillbirth. This study aims to identify factors reported by women influencing weight management behaviours during pregnancy. METHODS: A systematic search was conducted in five databases from inception to 2019 and updated in 2021. Qualitative studies involving pregnant or post-partum women, from high-income countries, examining women's experiences of weight management during pregnancy were included. Meta-ethnography was used to facilitate the meta-synthesis of 17 studies. RESULTS: Three themes were identified during the analysis: (1) Awareness and beliefs about weight gain and weight management, which included level of awareness and knowledge about dietary and exercise recommendations, risk perception and decision balance, perceived control over health and weight gain and personal insecurities. (2) Antenatal healthcare, women's experiences of their interactions with healthcare professionals during the antenatal period and the quality of the education received had an effect on women's behaviour. Further, our findings highlight the need for clear and direct information, and improved interactions with healthcare professionals, to better support women's weight management behaviours. (3) Social and environmental influence, the social judgement and stigmatization associated with overweight and obesity also acted as a negative influence in womens' engagement in weight management behaviours. CONCLUSION: Interventions developed to promote and maintain weight management behaviours during pregnancy should consider all levels of influence over women's behaviours, including women's level of awareness and beliefs, experiences in antenatal care, education provision and social influence.

The Experience of COVID-19 Visitor Restrictions among Families of People Living in Long-Term Residential Care Facilities during the First Wave of the Pandemic in Ireland.

Public health responses to COVID-19 in long-term residential care facilities (LTRCFs) have restricted family engagement with residents. These restrictions impact on quality of care and the psychosocial and emotional well-being of family caregivers. Following a national cross-sectional web-based survey, respondents were invited to provide personal reflections on visitor restrictions. This study aims to describe the consequences of these restrictions for individuals living in LTRCF and their families during the first wave of the COVID-19 pandemic. Data from open-ended questions contained within the survey were analyzed using Braun and Clarke's (2006) method of thematic analysis. Four themes were identified: 1. Altered Communication and Connection; 2. Emotional and Psychological Impact; 3. Protecting and Caring Role of Staff; 4. Family Role. Throughout the narrative accounts, it is evident that the visitor restrictions impacted on the emotional and mental well-being of families. Some respondents expressed frustration that they could not assist staff in essential care provision, reducing meaning and purpose in their own lives. COVID-19 LTRCF visitor restrictions made little distinction between those providing essential personal care and those who visit for social reasons. A partnership approach to care provision is important and should encompass strategies to maintain the psychosocial and emotional well-being of families and their relatives during times of self-isolating or restrictive measures.

The effect of discharge planning on length of stay and readmission rates of older adults in acute hospitals: A systematic review and meta-analysis of systematic reviews.

AIM: To examine the effectiveness of discharge planning on length of stay and readmission rates among older adults in acute hospitals. BACKGROUND: Discharge planning takes place in all acute hospital settings in many forms. However, it is unclear how it contributes to reducing patient length of stay in hospital and readmission rates. METHODS: Seven systematic reviews were identified and examined. All of the systematic reviews explored the impact of discharge planning on length of stay and readmission rates. RESULTS: A limited meta-analysis of the results in relation to length of stay indicates positive finding for discharge planning as an intervention (MD = -0.71(95% CI -1.05,-0.37; p = .0001)). However, further analysis of the broader findings in relation to length of stay indicates inconclusive or mixed results. In relation to readmission rates both meta-analysis and narrative analysis point to a reduced risk for older people where discharge planning has taken place (RR = 0.78 (95% CI: 0.72, 0.84; p = .00001)). The ability to synthesize results however is severely hampered by the diversity of approaches to research in this area. IMPLICATIONS FOR NURSING MANAGEMENT: It is unclear what impact discharge planning has on length of stay of older people. Indeed, while nurse mangers will be interested in gauging this impact on throughput and patient flow, it is questionable if length of stay is the correct outcome to measure when studying discharge planning as good discharge planning may increase length of stay. Readmission rates may be a more appropriate outcome measure but standardization of approach needs to be considered in this regard. This would assist nurse managers in assessing the impact of discharge planning processes.

A protocol for a systematic review of clinical practice guidelines for the antenatal management of dichorionic diamniotic twin pregnancy.

Overview: The protocol outlines the process designed to systematically review clinical practice guidelines (CPGs), addressing the antenatal management of dichorionic diamniotic (DCDA) twin pregnancies. Background: CPGs are statements that include recommendations intended to optimise patient care, that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. CPGs are typically created by scientific institutes, organisations and professional societies, and high-quality CPGs are fundamental to improve patient outcomes, standardise clinical practice and improve the quality of care. While CPGs are designed to improve the quality of care, to achieve this, the identification and appraisal of current international CPGs is required. Because twin pregnancies are identified as high-risk pregnancies, a systematic review of the CPGs in this field is a useful first step for establishing the required high level of care. Aim: The aim of the systematic review is to identify, appraise and examine published CPGs for the antenatal management of DCDA twin pregnancies, within high-income countries. Methods: We will identify published CPGs addressing any aspect of antenatal management of care in DCDA twin pregnancies, appraise the quality of the identified CPGs using the Appraisal of Guidelines for Research and Evaluation version 2 (AGREE II) the Appraisal of Guidelines Research and Evaluation - Recommendations excellence (AGREE-REX) instruments and examining the recommendations from the identified CPGs. Ultimately, this protocol aspires to clearly define the process for a reproducible systematic review of CPGs within a high-income country, addressing any aspect of antenatal management of DCDA twin pregnancies. PROSPERO registration: CRD42021248586 (24/06/2021).

Psychosocial Impact of COVID-19 Nursing Home Restrictions on Visitors of Residents With Cognitive Impairment: A Cross-Sectional Study as Part of the Engaging Remotely in Care (ERiC) Project.

Background: COVID-19 has disproportionately affected older people. Visiting restrictions introduced since the start of the pandemic in residential care facilities (RCFs) may impact negatively on visitors including close family, friends, and guardians. We examined the effects of COVID-19 visiting restrictions on measures of perceived loneliness, well-being, and carer quality of life (QoL) amongst visitors of residents with and without cognitive impairment (CI) in Irish RCFs. Methods: We created a cross-sectional online survey. Loneliness was measured with the UCLA brief loneliness scale, psychological well-being with the WHO-5 Well-being Index and carer QoL with the Adult Carer QoL Questionnaire (support for caring subscale). Satisfaction with care ("increased/same" and "decreased") was measured. A history of CI was reported by respondents. Sampling was by convenience with the link circulated through university mail lists and targeted social media accounts for 2 weeks in June 2020. Results: In all, 225 responses were included of which 202 noted whether residents had reported CI. Most of the 202 identified themselves as immediate family (91%) and as female (82%). The majority (67%) were aged between 45 and 64 years. Most (80%) reported that their resident had CI. Approximately one-third indicated reduced satisfaction (27%) or that restrictions had impaired communication with nursing home staff (38%). Median loneliness scores were 4/9, well-being scores 60/100 and carer QoL scores 10/15. Visitors of those with CI reported significantly lower well-being (p = 0.006) but no difference in loneliness (p = 0.114) or QoL (p = 0.305). Reported CI (p = 0.04) remained an independent predictors of lower WHO-5 scores, after adjusting for age, sex, RCF location, and dementia stage (advanced), satisfaction with care (reduced), and perception of staff support measured on the Adult Carer QoL Questionnaire. Conclusion: This survey suggests that many RCF visitors experienced low psychosocial and emotional well-being during the COVID-19 lockdown. Visitors of residents with CI report significantly poorer well-being as measured by the WHO-5 than those without. Additional research is required to understand the importance of disrupted caregiving roles resulting from visiting restrictions on well-being, particularly on visitors of residents with CI and how RCFs and their staff can support visitors to mitigate these.

Molecular Mechanisms of Anesthetic Neurotoxicity: A Review of the Current Literature.

Data from epidemiologic studies and animal models have raised a concern that exposure to anesthetic agents during early postnatal life may cause lasting impairments in cognitive function. It is hypothesized that this is due to disruptions in brain development, but the mechanism underlying this toxic effect remains unknown. Ongoing research, particularly in rodents, has begun to address this question. In this review we examine currently postulated molecular mechanisms of anesthetic toxicity in the developing brain, including effects on cell death pathways, growth factor signaling systems, NMDA and GABA receptors, mitochondria, and epigenetic factors. The level of evidence for each putative mechanism is critically evaluated, and we attempt to draw connections between them where it is possible to do so. Although there are many promising avenues of research, at this time no consensus can be reached as to a definitive mechanism of injury.

RAS pathway biomarkers for breast cancer prognosis.

Metastatic breast cancer is a highly heterogeneous, rapidly evolving and devastating disease that challenges our ability to find curative therapies. RAS pathway activation is an understudied research area in breast cancer. EGFR/RAS pathway activation is prevalent in breast cancer with poor prognosis. The prognostic RAS pathway biomarkers can be used to identify resistant tumour clones, stratify patients and guide therapies.

The prevalence and pathological correlates of orthostatic hypotension and its subtypes when measured using beat-to-beat technology in a sample of older adults living in the community.

BACKGROUND: beat-to-beat technology is increasingly used for investigating orthostatic intolerance (OI) but the prevalence of orthostatic hypotension (OH) diagnosed with this technology is unclear. OBJECTIVES: (i) to use beat-to-beat technology to define the prevalence of OH, (ii) to investigate the pathological correlates of OH, (iii) to report the diversity of postural BP responses. METHODS: cross-sectional study of adults ≥ 65 years. BP responses to a 3-min head-up tilt were analysed. RESULTS: of 326 participants, 203(62.3%) were females. The median (IQR) age was 73 (70-78). One hundred and ninety-one (58.6%) met standard (20 mmHg systolic/10 mmHg diastolic) criteria for OH. The prevalence was higher in females (60.1% F versus 56.1% M); 47% were arteriolar subtype, 33% were venular, 9% were mixed and 11.0% could not be classified. Morphological analysis identified 102 subjects with 'small drop, overshoot', 131 with 'medium drop, slow recovery' and 31 with 'large drop, nonrecovery'. Those with OH had a lower BMI (P = 0.02), a higher resting heart rate (P = 0.005), were more likely to take a psychotropic (P = 0.02), have vertigo (P = 0.004) and report OI (P = 0.02). The 95th centile for the duration of systolic BP (SYSBP) decay >20 mmHg was 175 s and the slope of systolic BP decay was 4.75 mmHg/s. The 5th centile for percentage recovery of SYSBP was 81.4%. CONCLUSION: (i) beat-to-beat methods identify a higher prevalence of OH than sphygmomanometry, (ii) the pathological correlates of OH diagnosed in this manner are similar to those described for sphygmomanometry, (iii) there is a diverse pattern of orthostatic BP decay that could be used in future research to predict adverse outcomes in OH.

Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome.

Maternal immune activation during prenatal development, including treatment with the viral RNA mimic, polyriboinosinic-polyribocytidilic acid (poly IC), serves as a widely used animal model to induce behavioral deficits reminiscent of schizophrenia and related disease. Here, we report that massive cytokine activation after a single dose of poly IC in the prenatal period is associated with lasting working memory deficits in adult offspring. To explore whether dysregulated gene expression in cerebral cortex, contributes to cognitive dysfunction, we profiled the cortical transcriptome, and in addition, mapped the genome-wide distribution of trimethylated histone H3-lysine 4 (H3K4me3), an epigenetic mark sharply regulated at the 5' end of transcriptional units. However, deep sequencing-based H3K4me3 mapping and mRNA profiling by microarray did not reveal significant alterations in mature cerebral cortex after poly IC exposure at embryonic days E17.5 or E12.5. At a small set of genes (including suppressor of cytokine signaling Socs3), H3K4me3 was sensitive to activation of cytokine signaling in primary cultures from fetal forebrain but adult cortex of saline- and poly IC-exposed mice did not show significant differences. A limited set of transcription start sites (TSS), including Disrupted-in-Schizophrenia 1 (Disc1), a schizophrenia risk gene often implicated in gene-environment interaction models, showed altered H3K4me3 after prenatal poly IC but none of these differences survived after correcting for multiple comparisons. We conclude that prenatal poly IC is associated with cognitive deficits later in life, but without robust alterations in epigenetic regulation of gene expression in the cerebral cortex.

Service user experience of adapted dialectical behaviour therapy in a community adult mental health setting.

BACKGROUND: Dialectical behaviour therapy (DBT), a skill-based cognitive behavioural treatment, is increasingly used in the treatment of borderline personality disorder (BPD). AIMS: The study examined service users' perspective on the effectiveness of an adapted DBT programme, delivered within a community adult mental health setting. METHODS: Semi-structured interviews and focus groups were conducted with eight participants with a diagnosis of BPD about their experience of the programme. RESULTS: Thematic analysis focused on two key themes: evaluation of therapy and treatment impact. Therapy-specific factors and personal challenges emerged as important themes. Treatment impact raised issues relating to a renewed sense of identity and changes in daily life. CONCLUSIONS: The study describes the positive and negative experiences of service users with BPD attending an adapted DBT programme.

White matter neuron alterations in schizophrenia and related disorders.

Increased density and altered spatial distribution of subcortical white matter neurons (WMNs) represents one of the more well replicated cellular alterations found in schizophrenia and related disease. In many of the affected cases, the underlying genetic risk architecture for these WMN abnormalities remains unknown. Increased density of neurons immunoreactive for Microtubule-Associated Protein 2 (MAP2) and Neuronal Nuclear Antigen (NeuN) have been reported by independent studies, though there are negative reports as well; additionally, group differences in some of the studies appear to be driven by a small subset of cases. Alterations in markers for inhibitory (GABAergic) neurons have also been described. For example, downregulation of neuropeptide Y (NPY) and nitric oxide synthase (NOS1) in inhibitory WMN positioned at the gray/white matter border, as well as altered spatial distribution, have been reported. While increased density of WMN has been suggested to reflect disturbance of neurodevelopmental processes, including neuronal migration, neurogenesis, and cell death, alternative hypotheses--such as an adaptive response to microglial activation in mature CNS, as has been described in multiple sclerosis--should also be considered. We argue that larger scale studies involving hundreds of postmortem specimens will be necessary in order to clearly establish the subset of subjects affected. Additionally, these larger cohorts could make it feasible to connect the cellular pathology to environmental and genetic factors implicated in schizophrenia, bipolar disorder, and autism. These could include the 22q11 deletion (Velocardiofacial/DiGeorge) syndrome, which in some cases is associated with neuronal ectopias in white matter.

Setdb1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B.

Histone methyltransferases specific for the histone H3-lysine 9 residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on neuronal function and behavior remain unexplored. Here, we report that transgenic mice with increased Setdb1 expression in adult forebrain neurons show antidepressant-like phenotypes in behavioral paradigms for anhedonia, despair, and learned helplessness. Chromatin immunoprecipitation in conjunction with DNA tiling arrays (ChIP-chip) revealed that genomic occupancies of neuronal Setdb1 are limited to <1% of annotated genes, which include the NMDA receptor subunit NR2B/Grin2B and other ionotropic glutamate receptor genes. Chromatin conformation capture and Setdb1-ChIP revealed a loop formation tethering the NR2B/Grin2b promoter to the Setdb1 target site positioned 30 kb downstream of the transcription start site. In hippocampus and ventral striatum, two key structures in the neuronal circuitry regulating mood-related behaviors, Setdb1-mediated repressive histone methylation at NR2B/Grin2b was associated with decreased NR2B expression and EPSP insensitivity to pharmacological blockade of NR2B, and accelerated NMDA receptor desensitization consistent with a shift in NR2A/B subunit ratios. In wild-type mice, systemic treatment with the NR2B antagonist, Ro25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol], and hippocampal small interfering RNA-mediated NR2B/Grin2b knockdown resulted in behavioral changes similar to those elicited by the Setdb1 transgene. Together, these findings point to a role for neuronal Setdb1 in the regulation of affective and motivational behaviors through repressive chromatin remodeling at a select set of target genes, resulting in altered NMDA receptor subunit composition and other molecular adaptations.

A simple method for improving the specificity of anti-methyl histone antibodies.

Antibodies differentiating between the mono-, di- and trimethylated forms of specific histone lysine residues are a critical tool in epigenome research, but show variable specificity, potentially limiting comparisons across studies and between samples. Using trimethyl histone H3 lysine 4 (H3K4me3)-a mark enriched at transcription start sites (TSS) of active genes-as an example, we describe how simple co-incubation with synthetic peptide of the K4me2 modification leads to increased specificity for K4me3 and a much sharper peak distribution proximal to TSS following chromatin immunoprecipitation and massively parallel sequencing (ChIP-Seq).

A systematic review evaluating the impact of post-registration nursing and midwifery education on practice.

Given the current focus on evidence-based practice, it is surprising that there is a dearth of systematic evidence of the impact on practice of post-registration nursing and midwifery education. The systematic review presented here formed part of a national review of post-registration nursing and midwifery education in Ireland [Health Service Executive, 2008. Report of the Post-registration Nursing and Midwifery Education Review Group: Changing practice to support service delivery. Health Service Executive, Dublin]. The review focuses specifically on the impact on practice from the perspective of nurses, midwives, patients, carers, education and health service providers. Sixty-one (61) studies met the criteria set. These studies were mainly of a retrospective and descriptive nature, often with small cohorts, set within one educational setting. The findings indicate that students benefit from post-registration programmes in relation to changes in attitudes, perceptions, knowledge and in skill acquisition. There is also some evidence that students apply their newly acquired attitudes, knowledge and skills. There is however limited evidence of the direct impact on organisational and service delivery changes, and on benefits to patients and carers. It can be concluded that the impact of post-registration nursing and midwifery education on practice has yet to be fully explored through a more systematic and coherent programme evaluation approach.

Cingulate white matter neurons in schizophrenia and bipolar disorder.

BACKGROUND: Increased neuronal density in prefrontal, parietal, and temporal white matter of schizophrenia subjects is thought to reflect disordered neurodevelopment; however, it is not known if this cellular alteration affects the cingulate cortex and whether similar changes exist in bipolar disorder. METHOD: Eighty-two postmortem specimens (bipolar 15, schizophrenia 22, control 45) were included in this clinical study. Densities for two neuronal markers, neuron-specific nuclear protein (NeuN) and neuregulin 1 alpha (NRG), were determined in white matter up to 2.5 mm beneath the anterior cingulate cortex; density of NeuN immunopositive neurons (NeuN+) was also determined for a subset of cases in prefrontal cortex. Changes during normal development were monitored in a separate cohort of 14 brains. RESULTS: Both the schizophrenia and bipolar cohorts demonstrated a twofold increase in NeuN+ density in cingulate white matter; this effect could be attributed to approximately 25% of cases that exceeded the second standard deviation from control subjects. Similar changes were observed in prefrontal cortex. In contrast density of NRG expressing neurons was unaltered. Cases with increased NeuN+ densities in two-dimensional (2-D) counts also showed a pronounced, > fivefold elevation in NeuN+ nuclei per cubic millimeter. Additionally, the developmental cohort demonstrated a 75% decline in NeuN+ neuronal density during the first postnatal year but was stable thereafter. CONCLUSIONS: Increased neuronal density in white matter of cingulate cortex in schizophrenia provides further evidence that this alteration occurs in multiple cortical areas. Similar changes in some cases with bipolar illness suggest that the two disorders may share a common underlying defect in late prenatal or early postnatal neurodevelopment.

Novice researchers' reflection on conducting a focus group.

Focus group data collection can capture what is unknown about nurses' perceptions of routine patient care issues in clinical settings. Using Gibbs Reflective Cycle (1988) novice researchers Caroline O'Connor and Siobhan Murphy critically analysed the practicalities of conducting a focus group interview.

Amygdalar GABAergic-rich neural grafts attenuate anxiety-like behavior in rats.

Transplantation experiments have shown that neurologic deficits may be reversed by engrafting fresh tissue or engineered cells within dysfunctional neural circuitry. In experimental and clinical settings, this approach has provided insights into the pathology and treatment of neurologic diseases, primarily movement disorders. The present experiments were designed to investigate whether a similar strategy is feasible as a method to investigate, and perhaps repair, circuitry integral to emotional disorders. We focused on the amygdala, a macrostructure known to be involved in the expression of anxiety- and fear-related behaviors. GABAergic cell-rich suspensions were prepared from E17 rat lateral ganglionic eminence and engrafted bilaterally into the lateral and basolateral amygdaloid nuclei of young adult rats. After 6 weeks, increased numbers of GABAergic neurons were identified in the vicinity of the graft sites, and electron microscopy provided evidence for functional integration of transplanted cells. Rats with these grafts spent more time in the open arms of the elevated-plus maze, consistent with an anxioloytic-like phenotype. These rats were also less sensitive to the unconditioned anxiogenic effects of light on the acoustic startle response, although fear-potentiated startle was not affected, suggesting that the grafts produced an attenuation of unlearned fear but did not affect acquisition of conditioned fear. Our results raise the possibility that distinct components of emotion can be modulated by strategic neural engraftment.