Ocular Surface Parameters Predicting Patient Satisfaction After a Single Vectored Thermal Pulsation Procedure for Management of Symptomatic Meibomian Gland Dysfunction.

PURPOSE: To evaluate the ocular surface parameters that could predict patient satisfaction after single application of vectored thermal pulsation (VTP). METHODS: This is a retrospective interventional case series; it included consecutive patients who underwent bilateral VTP for management of symptomatic meibomian gland dysfunction (MGD). Patients received a full ocular surface evaluation. The outcome was patient subjective improvement during the first 3-4 months after 3 follow-up visits. For analysis, patients were divided into responders and nonresponders. RESULTS: Forty-nine patients received bilateral treatment, with 32 patients (65.3%) reporting subjective improvement after treatment. Responders had lower tear production (6.9 ± 5.9 mm vs. 13.6 ± 6.8 mm; t test P = 0.002), a higher corneal staining score (4.4 ± 5.0 vs. 0.43 ± 1.1; t test P = 0.003), and a higher conjunctival staining score (3.1 ± 2.4 vs. 1.5 ± 1.8; t test P = 0.023) and presented with a higher tear osmolarity (319.7 ± 23.22 mOsm/L vs. 306.9 ± 9.0 mOsm/L; t test P = 0.029) than the nonresponder group. We found no association between patient age, tear breakup time, Ocular Surface Disease Index score, tear lipid layer thickness, or MGD grading score, as measured before intervention, with patient-perceived success of treatment. No complications to treatment were noted, and no patient reported worsening of preexisting symptoms on follow-up. CONCLUSIONS: VTP can be effective in treating dry eye symptoms of patients with MGD. Our data show that objective findings of dry eye, as evidenced by lower tear production, higher corneal and conjunctival staining scores, and higher osmolarity, tend to be markers present in the group of patients responding positively to VTP.

Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: A case series analysis.

PRIMARY OBJECTIVES: To describe hormone profiles for pre-/post-menopausal women, to monitor time to resumption of menstruation among pre-menopausal women and to describe cortisol associated LH suppression and phasic variation in other sex hormones over timeMethods and procedures: This study determined amenorrhea duration and characterized acute (days 0-7) and chronic (months 1-6) gonadotropins [luteinizing hormone and follicle stimulating hormone (LH, FSH)], sex hormones (progesterone, estradiol) and stress hormone (cortisol) profiles. Women were pre-menopausal (n = 3) or post-menopausal (n = 3). Among pre-menopausal women, menstrual cycle resolution and phase association (luteal/follicular) was monitored using self-report monthly reproductive history questionnaires. This study compared post-TBI hormone profiles, stratified by menopausal status, to hormone levels from seven controls and described 6- and 12-month outcomes for these women. MAIN OUTCOMES AND RESULTS: Consistent with functional hypothalamic amenorrhea (FHA), menstruation resumption among pre-menopausal women occurred when serum cortisol normalized to luteal phase control levels. For post-menopausal women, serum cortisol reductions corresponded with resolution of suppressed LH levels. CONCLUSIONS: The stress of TBI results in anovulation and central hypothalamic-pituitary-ovarian (HPG) axis suppression. Future work will examine acute/chronic consequences of post-TBI hypercortisolemia and associated HPG suppression, the temporal association of HPG suppression with other neuroendocrine adaptations and how HPG suppression impacts multidimensional recovery for women with TBI.

Reductions in behavioral deficits and neuropathology in the R6/2 mouse model of Huntington's disease following transplantation of bone-marrow-derived mesenchymal stem cells is dependent on passage number.

INTRODUCTION: Huntington's disease (HD) is an autosomal dominant disorder caused by an expanded CAG repeat (greater than 38) on the short arm of chromosome 4, resulting in loss and dysfunction of neurons in the neostriatum and cortex, leading to cognitive decline, motor dysfunction, and death, typically occurring 15 to 20 years after the onset of motor symptoms. Although an effective treatment for HD has remained elusive, current studies using transplants of bone-marrow-derived mesenchymal stem cells provides considerable promise. This study further investigates the efficacy of these transplants with a focus on comparing how passage number of these cells may affect subsequent efficacy following transplantation. METHODS: In this study, mesenchymal stem cells isolated from the bone-marrow of mice (BM MSCs), were labeled with Hoechst after low (3 to 8) or high (40 to 50) numbers of passages and then transplanted intrastriatally into 5-week-old R6/2 mice, which carries the N-terminal fragment of the human HD gene (145 to 155 repeats) and rapidly develops symptoms analogous to the human form of the disease. RESULTS: It was observed that the transplanted cells survived and the R6/2 mice displayed significant behavioral and morphological sparing compared to untreated R6/2 mice, with R6/2 mice receiving high passage BM MSCs displaying fewer deficits than those receiving low-passage BM MSCs. These beneficial effects are likely due to trophic support, as an increase in brain derived neurotrophic factor mRNA expression was observed in the striatum following transplantation of BM MSCs. CONCLUSION: The results from this study demonstrate that BM MSCs hold significant therapeutic value for HD, and that the amount of time the cells are exposed to in vitro culture conditions can alter their efficacy.

Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington's disease.

Stem cells have gained significant interest as a potential treatment of neurodegenerative diseases, including Huntington's disease (HD). One source of these cells is adult neural stem cells (aNSCs), which differentiate easily into neuronal lineages. However, these cells are vulnerable to immune responses following transplantation. Another source is bone-marrow-derived mesenchymal stem cells (MSCs), which release neurotrophic factors and anti-inflammatory cytokines following transplantation, and are less vulnerable to rejection. The goal of this study was to compare the efficacy of transplants of MSCs, aNSCs, or cotransplants of MSCs and aNSCs for reducing deficits in a transgenic rat model of HD. HD rats received intrastriatal transplantations of 400,000 MSCs, aNSCs, or a combination of MSCs/aNSCs, while wild-type and HD controls were given vehicle. Rats were tested on the rotarod over the course of 20 weeks. The results indicated that transplants of: (a) aNSCs produced a strong immune response and conferred short-term behavioral benefits; (b) MSCs elicited a relatively weak immune response, and provided a longer term behavioral benefit; and (c) combined MSCs and aNSCs conferred long-term behavioral benefits and increased survival of the transplanted aNSCs. The finding that cotransplanting MSCs with aNSCs can prolong aNSC survival and provide greater behavioral sparing than when the transplants contains only aNSCs suggests that MSCs are capable of creating a more suitable microenvironment for aNSC survival. This cotransplantation strategy may be useful as a future therapeutic option for treating HD, especially if long-term survival of differentiated cells proves to be critically important for preserving lasting functional outcomes.

Gene expression profiles resulting from stable loss of p53 mirrors its role in tissue differentiation.

The tumor suppressor gene p53 is involved in a variety of cellular activities such as cellular stress responses, cell cycle regulation and differentiation. In our previous studies we have shown p53's transcription activating role to be important in osteoblast differentiation. There is still a debate in the literature as to whether p53 inhibits or promotes differentiation. We have found p53 heterozygous mice to show a p53 dependency on some bone marker gene expression that is absent in knockout mice. Mice heterozygous for p53 also show a higher incidence of osteosarcomas than p53 knockout mice. This suggests that p53 is able to modify the environment within osteoblasts. In this study we compare changes in gene expression resulting after either a transient or stable reduction in p53. Accordingly we reduced p53 levels transiently and stably in C2C12 cells, which are capable of both myoblast and osteoblast differentiation, and compared the changes in gene expression of candidate genes regulated by the p53 pathway. Using a PCR array to assay for p53 target genes, we have found different expression profiles when comparing stable versus transient knockdown of p53. As expected, several genes with profound changes after transient p53 loss were related to apoptosis and cell cycle regulation. In contrast, stable p53 loss produced a greater change in MyoD and other transcription factors with tissue specific roles, suggesting that long term loss of p53 affects tissue homeostasis to a greater degree than changes resulting from acute loss of p53. These differences in gene expression were validated by measuring promoter activity of different pathway specific genes involved in differentiation. These studies suggest that an important role for p53 is context dependent, with a stable reduction in p53 expression affecting normal tissue physiology more than acute loss of p53.

The moderating role of negative urgency on the prospective association between dietary restraint and binge eating.

It is well documented that negative urgency, a personality trait characterized by a tendency to act impulsively in the face of negative emotions, and dietary restraint independently increase risk to binge eat; however, it is unclear how these factors interact to alter risk for such behavior. It may be that individuals high on negative urgency, who also engage in dietary restraint, are at a greater risk to binge eat than individuals low on negative urgency. Accordingly, we sought to investigate whether negative urgency moderated the prospective association between dietary restraint and binge eating frequency among a sample of college women. We hypothesized that women who engaged in dietary restraint would report higher binge eating frequencies across the first semester of college and that this effect would be strengthened among individuals higher on negative urgency. Results indicated that negative urgency moderated the prospective association between dietary restraint and binge eating frequency. This effect was found to be "protective but reactive," such that low levels of dietary restraint protected against binge eating frequency at low to moderate levels of negative urgency, but this buffering effect was lost at high levels of negative urgency where binge eating frequency was equal across all levels of dietary restraint. These findings demonstrate that negative urgency and dietary restraint interact to differentially alter risk for binge eating frequency, and individuals high on negative urgency are at the greatest risk to engage in more frequent binge eating regardless of level of dietary restraint.

Exploring barriers and facilitators in eating disorders treatment among Latinas in the United States.

The purpose of this study was to explore facilitators and barriers that may contribute to, or prevent, the engagement and retention of Latinos in eating disorders (EDs) treatment. OBJECTIVE: The main objective of this investigation was to explore more fully the facilitators and barriers that may contribute to or prevent the engagement and retention of Latinos/as in EDs treatment. METHODS: A qualitative design based on grounded theory was used to guide in-depth interviews with 5 Latinas (mean age 31.2 years) with history of EDs and with 5 Latino mental health providers (mean age 36.4 years). RESULTS: Six main themes were found in the discussion with patients and mental health providers: immigration stress, treatment experience in the U.S., facilitators of help seeking, barriers to help seeking, treatment needs, and facilitators of treatment retention. For patients, lack of information about EDs and lack of bilingual treatment were identified as practical barriers. Other emotional factors such as stigma, fear of not being understood, family privacy and not being ready to change were identified as barriers to seeking help. Among facilitator factors that encouraged patients to seek help, the most salient were the perception of the severity of the ED and emotional distress. For treatment retention, family support was a key element among patients. For providers, offering short-term treatment and directive treatment were seen as relevant factors for treatment retention in Latinos. CONCLUSIONS: A culturally sensitive intervention model for Latinas with EDs in the U.S. is discussed addressing four levels: patient; family; providers; and system.

Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: behavioral and neuropathological analysis.

INTRODUCTION: Huntington's disease (HD) is an autosomal dominant disorder caused by an expanded CAG repeat on the short arm of chromosome 4 resulting in cognitive decline, motor dysfunction, and death, typically occurring 15 to 20 years after the onset of motor symptoms. Neuropathologically, HD is characterized by a specific loss of medium spiny neurons in the caudate and the putamen, as well as subsequent neuronal loss in the cerebral cortex. The transgenic R6/2 mouse model of HD carries the N-terminal fragment of the human HD gene (145 to 155 repeats) and rapidly develops some of the behavioral characteristics that are analogous to the human form of the disease. Mesenchymal stem cells (MSCs) have shown the ability to slow the onset of behavioral and neuropathological deficits following intrastriatal transplantation in rodent models of HD. Use of MSCs derived from umbilical cord (UC) offers an attractive strategy for transplantation as these cells are isolated from a noncontroversial and inexhaustible source and can be harvested at a low cost. Because UC MSCs represent an intermediate link between adult and embryonic tissue, they may hold more pluripotent properties than adult stem cells derived from other sources. METHODS: Mesenchymal stem cells, isolated from the UC of day 15 gestation pups, were transplanted intrastriatally into 5-week-old R6/2 mice at either a low-passage (3 to 8) or high-passage (40 to 50). Mice were tested behaviorally for 6 weeks using the rotarod task, the Morris water maze, and the limb-clasping response. Following behavioral testing, tissue sections were analyzed for UC MSC survival, the immune response to the transplanted cells, and neuropathological changes. RESULTS: Following transplantation of UC MSCs, R6/2 mice did not display a reduction in motor deficits but there appeared to be transient sparing in a spatial memory task when compared to untreated R6/2 mice. However, R6/2 mice receiving either low- or high-passage UC MSCs displayed significantly less neuropathological deficits, relative to untreated R6/2 mice. CONCLUSIONS: The results from this study demonstrate that UC MSCs hold promise for reducing the neuropathological deficits observed in the R6/2 rodent model of HD.

Early cognitive dysfunction in the HD 51 CAG transgenic rat model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat that produces choreic movements, which are preceded by cognitive deficits. The HD transgenic rat (tgHD), which contains the human HD mutation with a 51 CAG repeat allele, exhibits motor deficits that begin when these rats are 12 months of age. However, there are no reports of cognitive dysfunction occurring prior to this. To assess whether cognitive dysfunction might precede motor deficits in tgHD rats, one group of 9-month-old male rats with homozygotic mutated genes and one group of wild-type (WT) rats underwent three testing phases in a unique Spatial Operant Reversal Test (SORT) paradigm, as well as assessment of spontaneous motor activity. After testing, morphological and histological examination of the brains were made. Results indicated that tgHD rats acquired the cued-response (Phase 1) portion of the SORT, but made significantly more errors during the reversal (Phase 2) and during the pseudorandomized reversals (Phase 3) portion of the study, when compared to WT rats. Analysis of the data using mathematical principles of reinforcement revealed no memory, motor, or motivational deficits. These results indicate that early cognitive dysfunction, as measured by the SORT, occur prior to motor deficits, gross anatomical changes, or cell loss in the tgHD rat with 51 CAG repeats, and suggest that this protocol could provide a useful screen for therapeutic studies.

Boxing training for patients with Parkinson disease: a case series.

BACKGROUND AND PURPOSE: A nontraditional form of exercise recently applied for patients with Parkinson disease (PD) is boxing training. The primary purpose of this case series is to describe the effects of disease severity and duration of boxing training (short term and long term) on changes in balance, mobility, and quality of life for patients with mild or moderate to severe PD. The feasibility and safety of the boxing training program also were assessed. CASE DESCRIPTION: Six patients with idiopathic PD attended 24 to 36 boxing training sessions for 12 weeks, with the option of continuing the training for an additional 24 weeks (a seventh patient attended sessions for only 4 weeks). The 90-minute sessions included boxing drills and traditional stretching, strengthening, and endurance exercises. Outcomes were tested at the baseline and after 12, 24, and 36 weeks of boxing sessions (12-, 24-, and 36-week tests). The outcome measures were the Functional Reach Test, Berg Balance Scale, Activities-specific Balance Confidence Scale, Timed "Up & Go" Test, Six-Minute Walk Test, gait speed, cadence, stride length, step width, activities of daily living and motor examination subscales of the Unified Parkinson Disease Rating Scale, and Parkinson Disease Quality of Life Scale. OUTCOMES: Six patients completed all phases of the case series, showed improvements on at least 5 of the 12 outcome measures over the baseline at the 12-week test, and showed continued improvements at the 24- and 36-week tests. Patients with mild PD typically showed improvements earlier than those with moderate to severe PD. DISCUSSION: Despite the progressive nature of PD, the patients in this case series showed short-term and long-term improvements in balance, gait, activities of daily living, and quality of life after the boxing training program. A longer duration of training was necessary for patients with moderate to severe PD to show maximal training outcomes. The boxing training program was feasible and safe for these patients with PD.

Fasting increases risk for onset of binge eating and bulimic pathology: a 5-year prospective study.

Although adolescent girls with elevated dietary restraint scores are at increased risk for future binge eating and bulimic pathology, they do not eat less than those with lower restraint scores. The fact that only a small proportion of individuals with elevated dietary restraint scores develop bulimic pathology suggests that some extreme but rare form of dietary restriction may increase risk for this disturbance. The authors tested the hypothesis that fasting (going without eating for 24 hr for weight control) would be a more potent predictor of binge eating and bulimic pathology onset than dietary restraint scores using data from 496 adolescent girls followed over 5 years. Results confirmed that only 23% of participants with elevated dietary restraint scores reported fasting. Furthermore, fasting generally showed stronger and more consistent predictive relations to future onset of recurrent binge eating and threshold/subthreshold bulimia nervosa over 1- to 5-year follow-up relative to dietary restraint, though the former effects were only significantly stronger than the latter for some comparisons. Results provide preliminary support for the hypothesis that fasting is a stronger risk factor for bulimic pathology than is self-reported dieting.

Supplementary feeding at milking and minimum milking interval effects on cow traffic and milking performance in a pasture-based automatic milking system.

In extensive pastoral dairy farming systems herds graze 12 months of the year with the majority fed a near-100% pasture or conserved pasture diet. The viability of automatic milking in these systems will depend partly upon the amount of supplementary feed necessary to encourage cows to walk from the pasture to the milking unit but also on the efficient use of the automatic milking system (AMS). This paper describes a study to determine the importance of offering concentrate in the milking unit and the effect of minimum milking interval on cow movement and milking performance in a pasture-based AMS. The effects of feeding rate (FR0=0 kg or FR1=1 kg crushed barley/d) and minimum milking interval (MM6=6 h or MM12=12 h) on cow movement and behaviour during milking were studied in a multi-factorial cross-over (feeding level only, 4 weeks per treatment) experiment involving 27 mixed-breed cows milked through a single AMS. Feeding 1 kg barley in the milking unit resulted in a higher visiting frequency to the pre-selection unit (FR0=4.6 visits/d, FR1=5.4 visits/d, sed=0.35, P<0.05) and a higher yield (FR0=22.5 kg/d, FR1=23.6 kg/d, sed=0.385, P<0.01) but had no effect on milking frequency (FR0=1.6 milkings/d, FR1=1.7 milkings/d, sed=0.04, NS). Minimum milking interval was the major factor influencing milking frequency (MM6=1.9, MM12=1.4 milkings/d, sed=0.15, P<0.01). The absence of feeding in the milking unit had no negative effect on behaviour during milking or the number of cows that had to be manually driven from the paddock. The results show that automatic milking can be combined with a near-100% pasture diet and that milking interval is an important determinant for maximizing milk harvested per AMS.

The effect of pre-milking teat-brushing on milk processing time in an automated milking system.

Cow throughput in an automatic milking system (AMS) is limited by system parameters such as the time required for pre-milking udder preparation and cup attachment, physiological responses of the cow (such as milk let-down and milking-out rate), milking machine features and cow behaviour. A single-factor cross-over design was used to investigate the effect of pre-milking teat brushing on milk processing time in an AMS operating in an extensive grazing farming system. Teat brushing consisted of two roller brushes tracking up each teat three times (total brushing time of up to 45 s/cow). Cows were allocated to one of two treatment groups with either no brushing (NB) or brushing (B) for a 4-week period before being changed to the other treatment. Teat brushing resulted in shorter average cups-on-time (B = 506.1 s, NB = 541.0 s, P = 0.0001), longer average milk processing time (B = 10.30 min, NB = 9.76 min, P = 0.001) and no difference in daily milk yield (B = 14.67, NB = 14.71 kg/cow, P = 0.826). There was no difference between the two treatments in the success of cup attachment (B = 3.76%, NB = 5.10% unsuccessful milking attempts, P = 0.285). The estimated time cost of pre-milking teat brushing was 53 min for every 100 milkings, equivalent to an additional 5-6 milkings for every 100 milkings by an AMS. The importance of these potential time savings is discussed in relation to automatic milking in farming systems that aim for a lower per cow milking frequency and high ratio of cows to AMS.