The incidence, characteristics and in-hospital mortality of non-ventilator-associated hospital-acquired pneumonia in regional Queensland: A retrospective descriptive study.

OBJECTIVE: The aim of this study was to determine the incidence, characteristics and in-hospital mortality of non-ventilator-associated hospital-acquired pneumonia (NV-HAP) in a regional (Modified Monash Model 2) Australian hospital. METHODS: All cases with NV-HAP were obtained from the Business Analysis and Decision Support (BADS) Unit between 1st January 2013 and 31st December 2018. Medical records were reviewed, and data pertaining to incidence, characteristics (age and gender), length of stay, co-morbidities (measured using the Charlson Comorbidity Index) and in-hospital mortality were extracted. Incidence rate was calculated as a proportion of NV-HAP cases per 1000 bed-days. DESIGN: A retrospective study design was used to review all cases of NV-HAP between 1 January 2013 and 31 December 2018 at a single regional Australian hospital. Using the Modified Monash Model (MMM), our regional setting is classified as a regional centre (MMM-2). SETTING: Rockhampton Hospital, Australia. PARTICIPANTS: Patient cases. MAIN OUTCOME MEASURES: Incidence rate, Incidence proportion, mortality. RESULTS: A total of 501 cases were identified with an incidence rate of 0.98 cases per 1000 bed-days over the study period 2013-2018. Cases with NV-HAP had a median age of 78.2 years (interquartile range 18.8), a median length of stay of 13.0 days (interquartile range 12.0) and a median Charlson Comorbidity Index score of 3.0 out of 39 (interquartile range 3.0), and a greater proportion was male (n = 297, 57%). The in-hospital mortality rate for NV-HAP cases was 18.9%. CONCLUSION: This study revealed an overall incidence rate of 0.98 cases per 1000 bed-days from 2013 to 2018 in a regional Australian hospital. In addition, this study provided the descriptive characteristics for patients with NV-HAP at our regional hospital.

Establishing key criteria to define and compare models of specialist palliative care: A mixed-methods study using qualitative interviews and Delphi survey.

BACKGROUND: Specialist palliative care services have various configurations of staff, processes and interventions, which determine how care is delivered. Currently, there is no consistent way to define and distinguish these different models of care. AIM: To identify the core components that characterise and differentiate existing models of specialist palliative care in the United Kingdom. DESIGN: Mixed-methods study: (1) semi-structured interviews to identify criteria, (2) two-round Delphi study to rank/refine criteria, and (3) structured interviews to test/refine criteria. SETTING/PARTICIPANTS: Specialist palliative care stakeholders from hospice inpatient, hospital advisory, and community settings. RESULTS: (1) Semi-structured interviews with 14 clinical leads, from eight UK organisations (five hospice inpatient units, two hospital advisory teams, five community teams), provided 34 preliminary criteria. (2) Delphi study: Round 1 (54 participants): thirty-four criteria presented, seven removed and seven added. Round 2 (30 participants): these 34 criteria were ranked with the 15 highest ranked criteria, including setting, type of care, size of service, diagnoses, disciplines, mode of care, types of interventions, 'out-of-hours' components (referrals, times, disciplines, mode of care, type of care), external education, use of measures, bereavement follow-up and complex grief provision. (3) Structured interviews with 21 UK service leads (six hospice inpatients, four hospital advisory and nine community teams) refined the criteria from (1) and (2), and provided four further contextual criteria (team purpose, funding, self-referral acceptance and discharge). CONCLUSION: In this innovative study, we derive 20 criteria to characterise and differentiate models of specialist palliative care - a major paradigm shift to enable accurate reporting and comparison in practice and research.

The impact of a new public health approach to end-of-life care: A systematic review.

BACKGROUND: Communities play an increasingly significant role in their own health and social care, and evidence demonstrates the positive impact of this work on a range of health outcomes. Interest is building regarding the application of the principles of the new public health approach to those facing the end of life and their families and communities. AIM: To review the evidence relating to the impact of a new public health approach to end-of-life care, specifically as this applies to efforts to strengthen community action. DESIGN: A systematic review employing narrative synthesis. Both meta-ethnography and the use of descriptive statistics supported analysis. DATA SOURCES: Eight databases (AMED, ASSIA, BiblioMap, CINAHL, Cochrane Reviews, EMBASE, MEDLINE and PsycINFO) were searched from the earliest record to March 2015 using set eligibility criteria. RESULTS: Eight articles were included in the analysis. Three main themes emerged from the meta-ethnography: making a practical difference, individual learning and personal growth and developing community capacity. The quantitative findings mapped to the meta-ethnography and demonstrated that engaging communities can lead to improved outcomes for carers such as decreased fatigue or isolation, increase in size of caring networks and that wider social networks can influence factors such as place of death and involvement of palliative care services. CONCLUSION: Evidence exists for the impact of community engagement in end-of-life care. Impact assessment should be an integral part of future initiatives and policy makers should recognise that these approaches can influence complex issues such as carer support, community capacity, wellbeing and social isolation.

Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.

Is the alcohol deprivation effect genetically mediated? Studies with HXB/BXH recombinant inbred rat strains.

BACKGROUND: Two features of alcohol addiction that have been widely studied in animal models are relapse drinking following periods of alcohol abstinence and the escalation of alcohol consumption after chronic continuous or intermittent alcohol exposure. The genetic contribution to these phenotypes has not been systematically investigated. METHODS: HXB/BXH recombinant inbred (RI) rat strains were given access to alcohol sequentially as follows: alcohol (10%) as the only fluid for 1 week; alcohol (10%) and water in a 2-bottle choice paradigm for 7 weeks ("pre-alcohol deprivation effect [ADE] alcohol consumption"); 2 weeks of access to water only (alcohol deprivation); and 2 weeks of reaccess to 10% alcohol and water ("post-ADE alcohol consumption"). The periods of deprivation and reaccess to alcohol were repeated 3 times. The ADE was defined as the amount of alcohol consumed in the first 24 hours after deprivation minus the average daily amount of alcohol consumed in the week prior to deprivation. Heritability of the phenotypes was determined by analysis of variance, and quantitative trait loci (QTLs) were identified. RESULTS: All strains showed increased alcohol consumption, compared to the predeprivation period, in the first 24 hours after each deprivation (ADE). Broad-sense heritability of the ADEs was low (ADE1, 9.1%; ADE2, 26.2%; ADE3, 16.3%). Alcohol consumption levels were relatively stable over weeks 2 to 7. Post-ADE alcohol consumption levels consistently increased in some strains and were decreased or unchanged in others. Heritability of pre- and post-ADE alcohol consumption was high and increased over time (week 2, 38.5%; week 7, 51.1%; week 11, 56.8%; week 15, 63.3%). QTLs for pre- and post-ADE alcohol consumption were similar, but the strength of the QTL association with the phenotype decreased over time. CONCLUSIONS: In the HXB/BXH RI rat strains, genotypic variance does not account for a large proportion of phenotypic variance in the ADE phenotype (low heritability), suggesting a role of environmental factors. In contrast, a large proportion of the variance across the RI strains in pre- and post-ADE alcohol consumption is due to genetically determined variance (high heritability).

Listening differently to patients can help enhance their experience of care.

Receiving and responding to timely feedback from patients is a vital component of high-quality care. However, this has long been a neglected area, especially for people receiving end-of-life services.

Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.

Using volunteers to improve access to community rehabilitation in palliative care: the St Christopher's Living Well at Home Team.

Background: UK hospices often provide outpatient rehabilitation services for people with advanced progressive illness. However, some people are unable to travel, leading to inequity in rehabilitation access. Objectives: The Living Well at Home Team (LWAHT) at St Christopher's Hospice aimed to evaluate whether using volunteers to support rehabilitation in peoples' homes improved the reach of rehabilitation for people living in underserved localities and if it supported people to optimise their functional independence. Methods: This service improvement project evaluated hospice rehabilitation uptake during the implementation of volunteer-supported community rehabilitation. Following assessment by an LWAHT therapist, eligible people were matched with a trained volunteer who supported four to eight rehabilitation sessions in the person's home. The evaluation assessed uptake of the rehabilitation sessions. Mobility, wellbeing, and goal attainment outcomes were assessed by the Life-Space Assessment (LSA), General Health Questionnaire (GHQ), and Goal Attainment Scale (GAS), respectively. Results: In the first year, 183 patients were referred to the LWAHT; 123 were assessed and 96 received rehabilitation including 56 who were matched with a volunteer. Following volunteer support, patients reported significant improvements in mobility [LSA median 20 (IQR, 3.5-27.8)], general health [GHQ -2 (-5.25 to 0)], and achievement of goals [GAS T-score +8 (0-18.4)]. Conclusions: It was feasible to support community rehabilitation using hospice volunteers for people with advanced progressive illness. The LWAHT service also increased the uptake of hospice centre-based rehabilitation. Further work should test efficacy and identify patients requiring additional professional input. Key message: This is the first known study reporting on the use of trained rehabilitation volunteers to extend the reach of hospice rehabilitation services. People with limited access to the hospice, because of geographical location or personal circumstances, valued and benefited from tailored rehabilitation supported by the volunteers in their own homes.

A catechol-O-methyltransferase that is essential for auditory function in mice and humans.

We have identified a previously unannotated catechol-O-methyltranferase (COMT), here designated COMT2, through positional cloning of a chemically induced mutation responsible for a neurobehavioral phenotype. Mice homozygous for a missense mutation in Comt2 show vestibular impairment, profound sensorineuronal deafness, and progressive degeneration of the organ of Corti. Consistent with this phenotype, COMT2 is highly expressed in sensory hair cells of the inner ear. COMT2 enzymatic activity is significantly reduced by the missense mutation, suggesting that a defect in catecholamine catabolism underlies the auditory and vestibular phenotypes. Based on the studies in mice, we have screened DNA from human families and identified a nonsense mutation in the human ortholog of the murine Comt2 gene that causes nonsyndromic deafness. Defects in catecholamine modification by COMT have been previously implicated in the development of schizophrenia. Our studies identify a previously undescribed COMT gene and indicate an unexpected role for catecholamines in the function of auditory and vestibular sense organs.

ALERT: mix-ups between conventional and lipid formulations of amphotericin B can be extremely dangerous.

In this column, the authors review Amphotericin B incidents reported Although amphotericin B may be less commonly used today because to ISMP Canada. In particular, we focus on incidents reported to have of alternative antifungal agents available, incident reports suggest resulted in patient harm due to mix-ups between the conventional there continues to be a need to alert practitioners to the different (non-lipid)formulation and lipid formulations of amphotericin B. formulations, and to implement system safety strategies.

Heart failure-the experience of living with end-stage heart failure and accessing care across settings.

BACKGROUND: Heart failure is a complex clinical syndrome affecting an increasing number of the ageing population. Patients and carers require increasing input from specialist palliative care services to both manage symptoms and access support in the last year of life. An integrated clinical service between the local cardiology team at Princess Royal University Hospital and the palliative care team at St. Christopher's Hospice was piloted for patients with end-stage heart failure in Bromley in Kent, UK. This study explored views of patients and carers who participated in the integrated pilot service. METHODS: A qualitative study was conducted in which a convenience sample of patients and carers were invited to participate in focus groups: two bereaved carer groups (n=2, n=2); one patient group (n=4), held between 14th December 2018 and 18th January 2019. Participants were asked to describe their experiences of care received facilitated by a topic guide. Interviews were recorded, transcribed and coded using thematic analysis to identify common themes. RESULTS: Four patients (2:2 M:F) aged between 70 to 87 years and four female carers whom had cared for patients aged between 70 to 96 years who were since deceased, participated in this study. Overall, the service was positively received, and responses were mapped into four key areas; being diagnosed and living with heart failure, referral to palliative care, key helpful components of the care received and finally, unhelpful components of the new service in terms of care. Common themes emerged including understanding of heart failure and its trajectory, communication around palliative care, having a 'broker' for the system, recognition of carer's needs, service responsiveness, and feeling 'in control'. CONCLUSIONS: This qualitative study highlighted important considerations when developing an integrated heart failure and palliative care service. Education about heart failure for patients and carers, but also the integrated multidisciplinary team is crucial to improving detection of deterioration and facilitating communication around Advance Care Planning. The value of the 'expert-carer' should also be promoted and supported in chronic conditions. We recommend a focus on development of integrated services that enable joined-up care or single point of contact for patients and carers.

Alcohol drinking during early adolescence activates microglial cells and increases frontolimbic Interleukin-1 beta and Toll-like receptor 4 gene expression, with heightened sensitivity in male rats compared to females.

Adolescent drinking is risky because neural circuits in the frontal lobes are undergoing maturational processes important for cognitive function and behavioral control in adulthood. Previous studies have shown that myelinated axons in the medial prefrontal cortex (mPFC) are particularly sensitive to alcohol drinking, especially in males. Pro-inflammatory mediators like toll-like receptor 4 (TLR4) and interleukin-1 beta (IL1b) have been implicated in alcohol induced-inflammation and demyelination; thus, herein we test the hypothesis that voluntary alcohol drinking early in adolescence elicits a pro-inflammatory state that is more pronounced in the brain of males compared to females. Adolescent male and female Wistar rats self-administered sweetened alcohol or sweetened water from postnatal days 28-42 and separate sets of brains were processed for 1) immunolabeling for ionized calcium-binding adapter molecule 1 to analyze microglial cell morphology, or 2) qPCR analysis of gene expression of pro-inflammatory mediators. Binge drinking alcohol activated microglia in the mPFC and hippocampus of both males and females, suggesting that voluntary alcohol exposure initiates an inflammatory response. Il1b mRNA was upregulated in the mPFC of both sexes. Conversely, Tlr4 mRNA levels were elevated after drinking only in males, which could explain more robust effects of alcohol on myelin in this region in developing males compared to females. Il1b mRNA changes were not observed in the hippocampus, but alcohol elevated Tlr4 mRNA in both sexes, highlighting regional specificity in inflammatory responses to alcohol. Overall, these findings give insight into potential mechanisms by which low-to-moderate voluntary alcohol intake impacts the developing brain. This article is part of the special Issue on 'Vulnerabilities to Substance Abuse'.

Shortening time for access to alcohol drives up front-loading behavior, bringing consumption in male rats to the level of females.

BACKGROUND: Incentives to promote drinking ("happy hour") can encourage faster rates of alcohol consumption, especially in women. Sex differences in drinking dynamics may underlie differential health vulnerabilities relating to alcohol in women versus men. Herein, we used operant procedures to model the happy hour effect and gain insight into the alcohol drinking dynamics of male and female rats. METHODS: Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which rats had access to alcohol (self-administration session length). Rats were tested twice within the 12 h of the dark cycle, first at 2 h (early phase of the dark cycle, "early sessions") and then again at 10 h into the dark cycle (late phase of the dark cycle, "late sessions") with an 8-h break between the two sessions in the home cage. RESULTS: Adult females consumed significantly more alcohol (g/kg) than males in the 30-min sessions with the FR1 schedule of reinforcement when tested late in the dark cycle. Front-loading of alcohol was the primary factor driving higher consumption in females. Changing the schedule of reinforcement from FR1 to FR3 reduced total consumption. Notably, this manipulation had minimal effect on front-loading behavior in females, whereas front-loading behavior was significantly reduced in males when more effort was required to access alcohol. Compressing drinking access to 15 min to model a happy hour drove up front-loading behavior, generating alcohol drinking patterns in males that were similar to patterns in females (faster drinking and higher intake). CONCLUSIONS: This strategy could be useful for exploring sex differences in the neural mechanisms underlying alcohol drinking and related health vulnerabilities. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.

Cervical ripening at home or in-hospital-prospective cohort study and process evaluation (CHOICE) study: a protocol.

INTRODUCTION: The aim of the cervical ripening at home or in-hospital-prospective cohort study and process evaluation (CHOICE) study is to compare home versus in-hospital cervical ripening to determine whether home cervical ripening is safe (for the primary outcome of neonatal unit (NNU) admission), acceptable to women and cost-effective from the perspective of both women and the National Health Service (NHS). METHODS AND ANALYSIS: We will perform a prospective multicentre observational cohort study with an internal pilot phase. We will obtain data from electronic health records from at least 14 maternity units offering only in-hospital cervical ripening and 12 offering dinoprostone home cervical ripening. We will also conduct a cost-effectiveness analysis and a mixed methods study to evaluate processes and women/partner experiences. Our primary sample size is 8533 women with singleton pregnancies undergoing induction of labour (IOL) at 39+0 weeks' gestation or more. To achieve this and contextualise our findings, we will collect data relating to a cohort of approximately 41 000 women undergoing IOL after 37 weeks. We will use mixed effects logistic regression for the non-inferiority comparison of NNU admission and propensity score matched adjustment to control for treatment indication bias. The economic analysis will be undertaken from the perspective of the NHS and Personal Social Services (PSS) and the pregnant woman. It will include a within-study cost-effectiveness analysis and a lifetime cost-utility analysis to account for any long-term impacts of the cervical ripening strategies. Outcomes will be reported as incremental cost per NNU admission avoided and incremental cost per quality adjusted life year gained. RESEARCH ETHICS APPROVAL AND DISSEMINATION: CHOICE has been funded and approved by the National Institute of Healthcare Research Health Technology and Assessment, and the results will be disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN32652461.

Protracted withdrawal from alcohol and drugs of abuse impairs long-term potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the stria terminalis.

The juxtacapsular bed nucleus of the stria terminalis (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of the amygdala. Here we show a form of long-term potentiation of the intrinsic excitability (LTP-IE) of jcBNST neurons in response to high-frequency stimulation of the stria terminalis. This LTP-IE, which was characterized by a decrease in the firing threshold and increased temporal fidelity of firing, was impaired during protracted withdrawal from self-administration of alcohol, cocaine, and heroin. Such impairment was graded and was more pronounced in rats that self-administered amounts of the drugs sufficient to maintain dependence. Dysregulation of the corticotropin-releasing factor (CRF) system has been implicated in manifestation of protracted withdrawal from dependent drug use. Administration of the selective corticotropin-releasing factor receptor 1 (CRF(1)) antagonist R121919 [2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine)], but not of the CRF(2) antagonist astressin(2)-B, normalized jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus, changes in the intrinsic properties of jcBNST neurons mediated by chronic activation of the CRF system may contribute to the persistent emotional dysregulation associated with protracted withdrawal.

Genetical genomic determinants of alcohol consumption in rats and humans.

BACKGROUND: We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. RESULTS: In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. CONCLUSION: Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well-defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption.

Sex Differences in the Neurobiology of Alcohol Use Disorder.

Sex differences may play a critical role in modulating how chronic or heavy alcohol use impacts the brain to cause the development of alcohol use disorder (AUD). AUD is a multifaceted and complex disorder driven by changes in key neurobiological structures that regulate executive function, memory, and stress. A three-stage framework of addiction (binge/intoxication; withdrawal/negative affect; preoccupation/anticipation) has been useful for conceptualizing the complexities of AUD and other addictions. Initially, alcohol drinking causes short-term effects that involve signaling mediated by several neurotransmitter systems such as dopamine, corticotropin releasing factor, and glutamate. With continued intoxication, alcohol leads to dysfunctional behaviors that are thought to be due in part to alterations of these and other neurotransmitter systems, along with alterations in neural pathways connecting prefrontal and limbic structures. Using the three-stage framework, this review highlights examples of research examining sex differences in drinking and differential modulation of neural systems contributing to the development of AUD. New insights addressing the role of sex differences in AUD are advancing the field forward by uncovering the complex interactions that mediate vulnerability.

Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence.

Experimenter-delivered alcohol decreases adult hippocampal neurogenesis and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis were observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggest a loss in neuronal turnover and indicate that the hippocampal neurogenic niche is highly vulnerable to alcohol.