Sex and pubertal variation in reward-related behavior and neural activation in early adolescents.

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9-13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Healthcare-associated infection impact with bioaerosol treatment and COVID-19 mitigation measures.

BACKGROUND: The real-world impact of breathing zone air purification and coronavirus disease 2019 (COVID-19) mitigation measures on healthcare-associated infections is not well documented. Engineering solutions to treat airborne transmission of disease may yield results in controlled test chambers or single rooms, but have not been reported on hospital-wide applications, and the impact of COVID-19 mitigation measures on healthcare-associated infection rates is unknown. AIM: To determine the impact of hospital-wide bioaerosol treatment and COVID-19 mitigation measures on clinical outcomes. METHODS: The impact of the step-wise addition of air disinfection technology and COVID-19 mitigation measures to standard multi-modal infection control on particle counts, viral and bacterial bioburden, and healthcare-associated infection rates was investigated in a 124-bed hospital (>100,000 patient-days over 30 months). FINDINGS AND CONCLUSION: The addition of air disinfection technology and COVID-19 mitigation measures reduced airborne ultrafine particles, altered hospital bioburden, and reduced healthcare-associated infections from 11.9 to 6.6 (per 1000 patient-days) and from 6.6 to 1.0 (per 1000 patient-days), respectively (P<0.0001, R2=0.86). No single technology, tool or procedure will eliminate healthcare-associated infections, but the addition of a ubiquitous facility-wide engineering solution at limited expense and with no alteration to patient, visitor or staff traffic or workflow patterns reduced infections by 45%. A similar impact was documented with the addition of comprehensive, restrictive, and labour- and material-intensive COVID-19 mitigation measures. To the authors' knowledge, this is the first direct comparison between traditional infection control, an engineering solution and COVID-19 mitigation measures.

Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility.

BACKGROUND: Several new genes and clinical subtypes have been identified since the publication in 2014 of the report of the last International Consensus Meeting on Epidermolysis Bullosa (EB). OBJECTIVES: We sought to reclassify disorders with skin fragility, with a focus on EB, based on new clinical and molecular data. METHODS: This was a consensus expert review. RESULTS: In this latest consensus report, we introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Other disorders with skin fragility, where blisters are a minor part of the clinical picture or are not seen because skin cleavage is very superficial, are classified as separate categories. These include peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility. Because of the common manifestation of skin fragility, these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. CONCLUSIONS: The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and genetic features of EB. What is already known about this topic? Epidermolysis bullosa (EB) is a group of genetic disorders with skin blistering. The last updated recommendations on diagnosis and classification were published in 2014. What does this study add? We introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors and natural history of EB are reviewed. Other disorders with skin fragility, e.g. peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility are classified as separate categories; these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. Linked Comment: Pope. Br J Dermatol 2020; 183:603.

General regression model for the subdistribution of a competing risk under left-truncation and right-censoring.

Left-truncation poses extra challenges for the analysis of complex time-to-event data. We propose a general semiparametric regression model for left-truncated and right-censored competing risks data that is based on a novel weighted conditional likelihood function. Targeting the subdistribution hazard, our parameter estimates are directly interpretable with regard to the cumulative incidence function. We compare different weights from recent literature and develop a heuristic interpretation from a cure model perspective that is based on pseudo risk sets. Our approach accommodates external time-dependent covariate effects on the subdistribution hazard. We establish consistency and asymptotic normality of the estimators and propose a sandwich estimator of the variance. In comprehensive simulation studies we demonstrate solid performance of the proposed method. Comparing the sandwich estimator with the inverse Fisher information matrix, we observe a bias for the inverse Fisher information matrix and diminished coverage probabilities in settings with a higher percentage of left-truncation. To illustrate the practical utility of the proposed method, we study its application to a large HIV vaccine efficacy trial dataset.

The human central nervous system transmits common synaptic inputs to distinct motor neuron pools during non-synergistic digit actions.

KEY POINTS: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. We quantified the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un-matched forces in different directions. We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control. The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire. ABSTRACT: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. Here we quantify the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles in humans during voluntary contractions. To remove confounds associated with previous studies, we used a task that required the two hand muscles to exert matched or un-matched forces in different directions. Despite the force production task consisting of uncommon digit force coordination patterns, we found that synaptic input to motor neurons is shared across all frequency bands, reflecting cortical and spinal inputs associated with force control. The coherence between discharge timings of the two pools of motor neurons was significant at the delta (0-5 Hz), alpha (5-15 Hz) and beta (15-35 Hz) bands (P < 0.05). These results suggest that correlated input to motor neurons of two hand muscles can occur even during tasks not belonging to a common behavioural repertoire and despite lack of common innervation. Moreover, we show that the extraction of activity from motor neurons during voluntary force control removes cross-talk associated with global EMG recordings, thus allowing direct in vivo interrogation of spinal motor neuron activity.

Rat strain response differences upon exposure to technical or alpha hexabromocyclododecane.

Hexabromocyclododecane (HBCD) is a brominated flame retardant which was recommended by a UN expert body under the Stockholm Convention to be eliminated from the global marketplace in 2011; however, due to its ability to persist in the environment, undergo long-range transport and bioaccumulate, it remains a concern for human health. The commercial mix of HBCD (T-HBCD) consists of α-HBCD, ß-HBCD and γ-HBCD. Although the γ-HBCD (79%) isomer is the predominant isomer of T-HBCD, the most bioaccumulative isomer detected in mammals is the α-HBCD isomer. This study was undertaken to investigate three rat strains treated with commercial grade (technical) HBCD or HBCD enriched with the α isomer (A-HBCD) and to examine strain- and sex-related differences in response to exposure. Female Sprague Dawley (SD), Wistar (WI) and Fischer F344 (FI) rats were exposed for 28 days to either T-HBCD or A-HBCD in feed, at doses of 0, 250, 1250 and 5000 mg/kg diet. The FI rodent strain was found to be the most sensitive to effects of HBCD based on the greatest number of significantly affected endpoints which indicated that T-HBCD primarily affected liver and thyroid, resulting in multiple health effects. Consequently, male FI were included in the study and exposed to T- and A-HBCD. Histopathological data supports previously reported effects of HBCD on the thyroid and endocrine system although the effects in FI rats are significantly elevated compared to other strains. As with T-HBCD, liver and thyroid were found to be target organs of A-HBCD. Sex differences, specifically in tissue concentration levels, immune response parameters and in number and severity of thyroid and liver lesions, following exposure to either T- or A-HBCD were apparent, with treatment eliciting a greater response in males. Residue analysis revealed that α-HBCD is more bioaccumulative than γ-HBCD in all rodent strains, with levels of HBCD in animals treated with A-HBCD several fold higher for all tissues tested (7-11 fold at the highest dose). Thus, residue data supports the selective uptake (implies there are differences in bioavailability and/or bioaccumulation; is this the case or do certain isomers simply have a longer half-life) of specific isomers, with α-HBCD > γ-HBCD. Taken together, our study highlights the importance of selecting the most appropriate strain and of including both sexes in studies to ensure that sex-related differences in response to test chemical is taken into consideration. Moreover, ours is the first study to show the effects of a sub-acute exposure to a diet containing only HBCD enriched for the α isomer, which better represents the isomer ratios present in the biota due to bioaccumulation.

ARCHITECTURAL PATTERNS FOR DIFFERENTIAL DIAGNOSIS OF PROLIFERATIVE BREAST LESIONS FROM HISTOPATHOLOGICAL IMAGES.

The differential diagnosis of proliferative breast lesions, benign usual ductal hyperplasia (UDH) versus malignant ductal carcinoma in situ (DCIS) is challenging. This involves a pathologist examining histopathologic sections of a biopsy using a light microscope, evaluating tissue structures for their architecture or size, and assessing individual cell nuclei for their morphology. Imposing diagnostic boundaries on features that otherwise exist on a continuum going from benign to atypia to malignant is a challenge. Current computational pathology methods have focused primarily on nuclear atypia in drawing these boundaries. In this paper, we improve on these approaches by encoding for both cellular morphology and spatial architectural patterns. Using a publicly available breast lesion database consisting of UDH and three different grades of DCIS, we improve the classification accuracy by 10% over the state-of-the-art method for discriminating UDH and DCIS. For the four way classification of UDH and the three grades of DCIS, our method improves the results by 6% in accuracy, 8% in micro-AUC, and 19% in macro-AUC.

Intranasal deferoxamine affects memory loss, oxidation, and the insulin pathway in the streptozotocin rat model of Alzheimer's disease.

Accumulation of metal and the accompanying increase in oxidative stress and inflammation plays an important role in neurodegenerative disease. Deferoxamine (DFO) is a metal chelator found to be beneficial in several animal models of neurodegenerative disease and insult including Alzheimer's disease, Parkinson's disease, stroke, and subarachnoid hemorrhage. In this study, we determine whether intranasally (IN) administered DFO is beneficial in the intracerebroventricular streptozotocin (ICV STZ) rat model of sporadic Alzheimer's disease, which is different from previous models in that it exhibits dysregulation of insulin metabolism as well as oxidative stress and inflammation. Surgical induction of the model included ICV injections of either STZ or citrate buffer (sham in rats), which were treated IN with either saline or DFO (n=10-15/group). Treatment started either before or after injection of STZ to induce the model, and continued throughout the study. IN treatment continued three times per week for three weeks before behavior tests started followed by eventual euthanasia with tissue collection. Spatial memory tests with the Morris water maze showed that STZ rats treated with IN DFO both before and after model induction had significantly shorter escape latencies. Pre-treatment with IN DFO also significantly decreased footslips on the tapered balance beam test. Brain tissue analyses showed DFO treatment decreased oxidation as measured by oxyblot and increased insulin receptor expression. These results further support the potential of IN DFO for use as a treatment for Alzheimer's disease, and show benefit in a non-amyloid/tau rodent model.

Transitions in pregnancy planning in women recruited for a large prospective cohort study.

STUDY QUESTION: Do the rates at which women transition among different intensities of pregnancy planning vary with age, marital status and race/ethnicity? SUMMARY ANSWER: Rates of transition from low or moderate pregnancy probability groups (PPGs) to higher PPGs vary by age, marital status and race/ethnicity. WHAT IS KNOWN ALREADY: The design of prospective studies of the effects of pre- and peri-conception exposures on fecundity, pregnancy and children's health is challenging because at any specific time only a small percentage of reproductive age women is attempting to conceive. To our knowledge, there has been no population-based, prospective study that repeatedly assessed pregnancy planning, which included women who were not already planning pregnancy at enrollment and whose ages spanned the female reproductive age range. STUDY DESIGN, SIZE, DURATION: A longitudinal study was carried out that repeatedly assessed pregnancy probability in 12 916 women for up to 21 months from January 2009 to September 2010. PARTICIPANTS/MATERIALS, SETTING, METHOD: We analyzed data from the National Children's Study Vanguard Study, a pilot study for a large-scale epidemiological birth cohort study of children and their parents. During the Vanguard Study, investigators followed population-based samples of reproductive age women in each of seven geographically dispersed and diverse study locations over time to identify when they sought to become pregnant, providing a unique opportunity to prospectively assess changes in pregnancy planning in a large sample of US women. At study entry and each follow-up contact, which occurred at 1, 3 or 6 month intervals depending on PPG, a questionnaire was used to assess behavior dimensions of pregnancy planning to assign women to low, moderate, high non-tryer and high tryer PPGs. MAIN RESULTS AND THE ROLE OF CHANCE: Crude rates of pregnancy increased with higher assigned PPG, validating the utility of the instrument. The initial PPG and probabilities of transitioning from low or moderate PPG to higher PPG or pregnancy varied with age, marital status and race/ethnicity. Women aged 25 to <35 years had shorter times to transition to higher PPGs or to pregnant compared with women <25 years. Women who were not currently married had longer times to transition from any initial PPG to pregnant, high tryer or high non-tryer status than currently married women. Non-Hispanic Black (NHB) and Hispanic women had shorter time to transition from low or moderate to high non-tryer than non-Hispanic White (NHW) women. NHB women also had shorter time to transition from low to high tryer than NHW women. High tryers are more likely to be aged 25 to <30 years, to be married, and to be Hispanic, NHB or other race/ethnicity than women in the low PPG. LIMITATIONS, REASONS FOR CAUTION: Loss to follow-up varied by age, marital status and race/ethnicity. Although weights were not developed for the Vanguard study, the self-weighting design minimizes the bias of unweighted analysis. Nonetheless, the SEs for some estimates may be under-estimated. WIDER IMPLICATIONS OF THE FINDINGS: Our results show that demographic characteristics are strong predictors of women's behaviors toward pregnancy. The results further show that frequent follow-up assessments of pregnancy planning behavior in large numbers of women are required to recruit an unbiased sample of preconception women. These findings will be useful to investigators designing prospective studies of fecundability, pregnancy outcomes and children's health. STUDY FUNDING/COMPETING INTERESTS: National Institutes of Health (contracts N01-HD53414, N01-HD63416, N01-HD53410, N01-HD53415, N01-HD53396, N01-HD53413 and N01-HD-53411; grant R21 ES016846) and by the University of California Irvine Center for Occupational and Environmental Health. No competing interests. TRIAL REGISTRATION NUMBER: None.

Functional interaction of histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) promotes breast cancer progression.

We have previously demonstrated that crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) facilitates breast cancer proliferation. However, the underlying mechanisms are largely unknown. Here, we report that expression of HDAC5 and LSD1 proteins were positively correlated in human breast cancer cell lines and tissue specimens of primary breast tumors. Protein expression of HDAC5 and LSD1 was significantly increased in primary breast cancer specimens in comparison with matched-normal adjacent tissues. Using HDAC5 deletion mutants and co-immunoprecipitation studies, we showed that HDAC5 physically interacted with the LSD1 complex through its domain containing nuclear localization sequence and phosphorylation sites. Although the in vitro acetylation assays revealed that HDAC5 decreased LSD1 protein acetylation, small interfering RNA (siRNA)-mediated HDAC5 knockdown did not alter the acetylation level of LSD1 in MDA-MB-231 cells. Overexpression of HDAC5 stabilized LSD1 protein and decreased the nuclear level of H3K4me1/me2 in MDA-MB-231 cells, whereas loss of HDAC5 by siRNA diminished LSD1 protein stability and demethylation activity. We further demonstrated that HDAC5 promoted the protein stability of USP28, a bona fide deubiquitinase of LSD1. Overexpression of USP28 largely reversed HDAC5-KD-induced LSD1 protein degradation, suggesting a role of HDAC5 as a positive regulator of LSD1 through upregulation of USP28 protein. Depletion of HDAC5 by shRNA hindered cellular proliferation, induced G1 cell cycle arrest, and attenuated migration and colony formation of breast cancer cells. A rescue study showed that increased growth of MDA-MB-231 cells by HDAC5 overexpression was reversed by concurrent LSD1 depletion, indicating that tumor-promoting activity of HDAC5 is an LSD1 dependent function. Moreover, overexpression of HDAC5 accelerated cellular proliferation and promoted acridine mutagen ICR191-induced transformation of MCF10A cells. Taken together, these results suggest that HDAC5 is critical in regulating LSD1 protein stability through post-translational modification, and the HDAC5-LSD1 axis has an important role in promoting breast cancer development and progression.

Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines.

This article summarizes recommendations reached following a systematic literature review and expert consensus on the diagnosis and management of cutaneous squamous cell carcinomas in people with epidermolysis bullosa. The guidelines are intended to help inform decision making by clinicians dealing with this complex complication of a devastating disease.

Second language as a compensatory resource for maintaining verbal fluency in bilingual immigrants with schizophrenia.

BACKGROUND AND OBJECTIVES: Due to the large migrations over the past three decades, large numbers of individuals with schizophrenia are learning a second language and being seen in clinics in that second language. We conducted within-subject comparisons to clarify the contribution of clinical, linguistic and bilingual features in the first and second languages of bilinguals with schizophrenia. METHODS: Ten bilingual Russian(L1) and Hebrew(L2) proficient patients, who developed clinical schizophrenia after achieving proficiency in both languages, were selected from 60 candidates referred for the study; they were resident in Israel 7-32 years with 3-10 years from immigration to diagnosis. Clinical, linguistic and fluency markers were coded in transcripts of clinical interviews. RESULTS: There was a trend toward more verbal productivity in the first language (L1) than the second language (L2). Clinical speech markers associated with thought disorder and cognitive impairment (blocking and topic shift) were similar in both languages. Among linguistic markers of schizophrenia, Incomplete syntax and Speech role reference were significantly more frequent in L2 than L1; Lexical repetition and Unclear reference demonstrated a trend in the same direction. For fluency phenomena, Discourse markers were more prevalent in L1 than L2, and Codeswitching was similar across languages, showing that the patients were attuned to the socio-pragmatics of language use. CONCLUSIONS: More frequent linguistic markers of schizophrenia in L2 show more impairment in the syntactic/semantic components of language, reflecting greater thought and cognitive dysfunction. Patients are well able to acquire a second language. Nevertheless, schizophrenia finds expression in that language. Finally, more frequent fluency markers in L1 suggests motivation to maintain fluency, evidenced in particular by codeswitched L2 lexical items, a compensatory resource.

An in vitro model of innate lymphoid cell function and differentiation.

Innate lymphoid cells (ILC) are RAG-independent lymphocytes with important roles in innate immunity, and include group-1 (natural killer (NK) cell, ILC1), group-2 (ILC2), and group-3 (lymphoid tissue inducer (LTi), NCR(+) ILC3) subsets. Group-3 ILC express Rorγt, produce interleukin (IL)-22, and are critically important in the normal function of mucosal tissues. Here, we describe a novel model cell line for the study of ILC function and differentiation. The parental MNK cell line, derived from NKR-P1B(+) fetal thymocytes, shows a capacity to differentiate in γc cytokines. One IL-7-responsive subline, designated MNK-3, expresses Rorγt and produces high levels of IL-22 in response to IL-23 and IL-1ß stimulation. MNK-3 cells display surface markers and transcript expression characteristic of group-3 ILC, including IL-7Rα (CD127), c-kit (CD117), CCR6, Thy1 (CD90), RANK, RANKL, and lymphotoxin (LTα1ß2). Using an in vitro assay of LTi cell activity, MNK-3 cells induce ICAM-1 and VCAM-1 expression on stromal cells in a manner dependent upon LTα1ß2 expression. A second IL-2-responsive subline, MNK-1, expresses several NK cell receptors, perforin and granzymes, and shows some cytotoxic activity. Thus, MNK-1 cells serve as a model of ILC1/NK development and differentiation, whereas MNK-3 cells provide an attractive in vitro system to study the function of ILC3/LTi cells.

Standardization and validation of a novel and simple method to assess lumbar dural sac size.

AIM: To develop and validate a simple, reproducible method to assess dural sac size using standard imaging technology. MATERIALS AND METHODS: This study was institutional review board-approved. Two readers, blinded to the diagnoses, measured anterior-posterior (AP) and transverse (TR) dural sac diameter (DSD), and AP vertebral body diameter (VBD) of the lumbar vertebrae using MRI images from 53 control patients with pre-existing MRI examinations, 19 prospectively MRI-imaged healthy controls, and 24 patients with Marfan syndrome with prior MRI or CT lumbar spine imaging. Statistical analysis utilized linear and logistic regression, Pearson correlation, and receiver operating characteristic (ROC) curves. RESULTS: AP-DSD and TR-DSD measurements were reproducible between two readers (r = 0.91 and 0.87, respectively). DSD (L1-L5) was not different between male and female controls in the AP or TR plane (p = 0.43; p = 0.40, respectively), and did not vary by age (p = 0.62; p = 0.25) or height (p = 0.64; p = 0.32). AP-VBD was greater in males versus females (p = 1.5 × 10(-8)), resulting in a smaller dural sac ratio (DSR) (DSD/VBD) in males (p = 5.8 × 10(-6)). Marfan patients had larger AP-DSDs and TR-DSDs than controls (p = 5.9 × 10(-9); p = 6.5 × 10(-9), respectively). Compared to DSR, AP-DSD and TR-DSD better discriminate Marfan from control subjects based on area under the curve (AUC) values from unadjusted ROCs (AP-DSD p < 0.01; TR-DSD p = 0.04). CONCLUSION: Individual vertebrae and L1-L5 (average) AP-DSD and TR-DSD measurements are simple, reliable, and reproducible for quantitating dural sac size without needing to control for gender, age, or height.

Increased blood-oxygen binding affinity in Tibetan and Han Chinese residents at 4200 m.

High-altitude natives are challenged by hypoxia, and a potential compensatory mechanism could be reduced blood oxygen-binding affinity (P50), as seen in several high-altitude mammalian species. In 21 Qinghai Tibetan and nine Han Chinese men, all resident at 4200 m, standard P50 was calculated from measurements of arterial PO2 and forehead oximeter oxygen saturation, which was validated in a separate examination of 13 healthy subjects residing at sea level. In both Tibetans and Han Chinese, standard P50 was 24.5 ± 1.4 and 24.5 ± 2.0 mmHg, respectively, and was lower than in the sea-level subjects (26.2 ± 0.6 mmHg, P < 0.01). There was no relationship between P50 and haemoglobin concentration (the latter ranging from 15.2 to 22.9 g dl(-1) in Tibetans). During peak exercise, P50 was not associated with alveolar-arterial PO2 difference or peak O2 uptake per kilogram. There appears to be no apparent benefit of a lower P50 in this adult high-altitude Tibetan population.

Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinson׳s disease.

Deferoxamine (DFO) has shown therapeutic promise for the treatment of Parkinson׳s disease (PD) as it has reduced both behavioral and biochemical deficits when injected into the brain of rodent models of PD. Intranasally administered DFO targets the brain directly but non-invasively and has been effective in animal models of stroke and Alzheimer׳s disease. In this study we sought to determine whether intranasal (IN) DFO could be neuroprotective for PD in a rat model. PD was induced with a unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, while sham surgery rats received saline injections. Rats were pre-treated three times with either IN DFO or saline (starting 4 days before 6-OHDA), and post-treated twice/wk for one month before behavioral tests. In the apomorphine-induced rotational test, IN DFO significantly decreased the number of contralateral turns after injection of apomorphine HCl (p<0.05). Also, IN DFO significantly decreased limb asymmetry in the rearing tube as measured with contralateral limb touches (p<0.05). The IN DFO treatment yielded a trend towards decreased contralateral foot-slips on the tapered balance beam, though the difference was not significant. Finally, IN DFO-treated rats had increased preservation of tyrosine hydroxylase immunoreactive neurons in the substantia nigra (p<0.05). These results confirm that DFO is beneficial in a 6-OHDA model and demonstrate improvement in motor deficits and dopaminergic neuronal survival with non-invasive intranasal delivery, making this an attractive potential treatment for PD.